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1.
  • Abbas, Sascha, et al. (författare)
  • Dietary intake of vitamin D and calcium and breast cancer risk in the European prospective investigation into cancer and nutrition
  • 2013
  • Ingår i: Nutrition and Cancer. - : Taylor & Francis. - 0163-5581 .- 1532-7914. ; 65:2, s. 178-187
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies assessing the effects of vitamin D or calcium intake on breast cancer risk have been inconclusive. Furthermore, few studies have evaluated them jointly. This study is the largest so far examining the association of dietary vitamin D and calcium intake with breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. During a mean follow-up of 8.8 yr, 7760 incident invasive breast cancer cases were identified among 319,985 women. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for pre- and postmenopausal breast cancer risk. Comparing the highest with the lowest quintile of vitamin D intake, HR and 95% CI were 1.07 (0.87-1.32) and 1.02 (0.90-1.16) for pre- and postmenopausal women, respectively. The corresponding HR and 95% CIs for calcium intake were 0.98 (0.80-1.19) and 0.90 (0.79-1.02), respectively. For calcium intake in postmenopausal women, the test for trend was borderline statistically significant (P(trend) = 0.05). There was no significant interaction between vitamin D and calcium intake and cancer risk (P(interaction) = 0.57 and 0.22 in pre- and postmenopausal women, respectively). In this large prospective cohort, we found no evidence for an association between dietary vitamin D or calcium intake and breast cancer risk.
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  • Aglago, Elom K., et al. (författare)
  • Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort
  • 2020
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:3, s. 6-666
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
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  • Aglago, Elom K., et al. (författare)
  • Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study
  • 2023
  • Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 128, s. 1529-1540
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.Methods: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.Results: Of 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99).Conclusions: Our findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.
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4.
  • Aglago, Elom K., et al. (författare)
  • Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk : A Case-Control Study Nested within a European Prospective Cohort
  • 2021
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 30:1, s. 182-192
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
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5.
  • Agudo, Antonio, et al. (författare)
  • Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
  • 2013
  • Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 34:6, s. 1244-1250
  • Tidskriftsartikel (refereegranskat)abstract
    • Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.
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6.
  • Agudo, Antonio, et al. (författare)
  • Impact of Cigarette Smoking on Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study
  • 2012
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:36, s. 4550-4557
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Our aim was to assess the impact of cigarette smoking on the risk of the tumors classified by the International Agency for Research on Cancer as causally associated with smoking, referred to as tobacco-related cancers (TRC). Methods The study population included 441,211 participants (133,018 men and 308,193 women) from the European Prospective Investigation Into Cancer and Nutrition. We investigated 14,563 participants who developed a TRC during an average follow-up of 11 years. The impact of smoking cigarettes on cancer risk was assessed by the population attributable fraction (AF(p)), calculated using the adjusted hazard ratios and 95% CI for current and former smokers, plus either the prevalence of smoking among cancer cases or estimates from surveys in representative samples of the population in each country. Results The proportion of all TRC attributable to cigarette smoking was 34.9% (95% CI, 32.5 to 37.4) using the smoking prevalence among cases and 36.2% (95% CI, 33.7 to 38.6) using the smoking prevalence from the population. The AF(p) were above 80% for cancers of the lung and larynx, between 20% and 50% for most respiratory and digestive cancers and tumors from the lower urinary tract, and below 20% for the remaining TRC. Conclusion Using data on cancer incidence for 2008 and our AF(p) estimates, about 270,000 new cancer diagnoses per year can be considered attributable to cigarette smoking in the eight European countries with available data for both men and women (Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Sweden, Denmark). 
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  • Agudo, Antonio, et al. (författare)
  • Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition
  • 2006
  • Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 15:12, s. 2427-2434
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries. The study includes 243 newly diagnosed cases of histologically confirmed gastric adenocarcinoma and 946 controls matched by center, age, sex, and date of blood collection. Genotypes were determined in nuclear DNA from WBCs. We found an increased risk of gastric cancer for homozygotes for C (histidine) variant in Y113H of EPHX1 (odds ratio, 1.91; 95% confidence interval, 1.19-3.07) compared with subjects with TC/TT. There was also a significant increased risk for smokers carrying at least one variant allele A in Ex7+129C > A (m4) of CYP1A1 and never smokers with null GSTT1 and allele A in the locus -3859G > A of CYP1A2. Most of these genes are involved in the activation and detoxification of polycyclic aromatic hydrocarbons, suggesting a potential role of these compounds in gastric carcinogenesis.
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  • Aleksandrova, Krasimira, et al. (författare)
  • A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk
  • 2015
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 107:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. Results: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P-difference = .87) and after excluding case patients diagnosed within the first four follow-up years. Conclusions: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.
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14.
  • Aleksandrova, Krasimira, et al. (författare)
  • Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study
  • 2014
  • Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 134:3, s. 612-621
  • Tidskriftsartikel (refereegranskat)abstract
    • Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; ptrend  = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; ptrend  = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.
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  • Aleksandrova, Krasimira, et al. (författare)
  • Adult weight change and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition
  • 2013
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 49:16, s. 3526-3536
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Weight change during adult life may reflect metabolic changes and influence colorectal cancer (CRC) development, but such role is not well established. We aimed to explore the association between adult weight change (from age 20 to 50) and CRC risk. In particular, we investigated differences according to colon and rectal cancer, sex and measures of attained adiposity. Methods: We included 201,696 participants from six participating countries in the European Prospective Investigation into Cancer and Nutrition (1992-2010). During a mean follow-up of 11.2 years 2384 (1194 in men and 1190 in women) incident CRC cases occurred. Cox proportional hazard models adjusted for body mass index at age 20 and lifestyle factors at study recruitment were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: After multivariable adjustment, each kg of weight gained annually from age 20 to 50 was associated with a 60% higher risk of colon cancer (95% CI 1.20-2.09), but not rectal cancer (HR 1.13, 95% CI 0.79-1.62, P-interaction = 0.04). The higher risk of colon cancer was restricted to people with high attained waist circumference at age 50 (HR 1.82, 95% CI 1.14-2.91, P-interaction = 0.02). Results were not different in men and women (P-interaction = 0.81). Conclusion(s): Adult weight gain, as reflected by attained abdominal obesity at age 50, increases colon cancer risk in both men and women. These data underline the importance of weight management and metabolic health maintenance in early adult life years for colon cancer prevention. (C) 2013 Elsevier Ltd. All rights reserved.
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  • Aleksandrova, Krasimira, et al. (författare)
  • Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer : results from the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2014
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 29:4, s. 261-275
  • Tidskriftsartikel (refereegranskat)abstract
    • A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.
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  • Aleksandrova, Krasimira, et al. (författare)
  • Circulating C-reactive protein concentrations and risks of colon and rectal cancer : a nested case-control study within the European Prospective Investigation into Cancer and Nutrition
  • 2010
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 172:4, s. 407-418
  • Tidskriftsartikel (refereegranskat)abstract
    • The authors investigated associations between serum C-reactive protein (CRP) concentrations and colon and rectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (1992-2003) among 1,096 incident cases and 1,096 controls selected using risk-set sampling and matched on study center, age, sex, time of blood collection, fasting status, menopausal status, menstrual cycle phase, and hormone replacement therapy. In conditional logistic regression with adjustment for education, smoking, nutritional factors, body mass index, and waist circumference, CRP showed a significant nonlinear association with colon cancer risk but not rectal cancer risk. Multivariable-adjusted relative risks for CRP concentrations of > or = 3.0 mg/L versus <1.0 mg/L were 1.36 (95% confidence interval (CI): 1.00, 1.85; P-trend = 0.01) for colon cancer and 1.02 (95% CI: 0.67, 1.57; P-trend = 0.65) for rectal cancer. Colon cancer risk was significantly increased in men (relative risk = 1.74, 95% CI: 1.11, 2.73; P-trend = 0.01) but not in women (relative risk = 1.06, 95% CI: 0.67, 1.68; P-trend = 0.13). Additional adjustment for C-peptide, glycated hemoglobin, and high density lipoprotein cholesterol did not attenuate these results. These data provide evidence that elevated CRP concentrations are related to a higher risk of colon cancer but not rectal cancer, predominantly among men and independently of obesity, insulin resistance, and dyslipidemia.
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  • Aleksandrova, Krasimira, et al. (författare)
  • Combined impact of healthy lifestyle factors on colorectal cancer : a large European cohort study
  • 2014
  • Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 12:1, s. 168-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.
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  • Aleksandrova, Krasimira, et al. (författare)
  • Development and validation of a lifestyle-based model for colorectal cancer risk prediction : the LiFeCRC score
  • 2021
  • Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.
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  • Aleksandrova, Krasimira, et al. (författare)
  • Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer
  • 2014
  • Ingår i: Hepatology. - : Wiley-Blackwell. - 0270-9139 .- 1527-3350. ; 60:3, s. 858-871
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however there is little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intra-hepatic bile duct (IBD) and gallbladder and bilary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137) or IBD (n=34). Using risk set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total, high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured and incidence rate ratios (IRRs) and 95% confidence intervals (CI-s) estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection and adiposity measures, higher concentrations of CRP, IL-6, C-peptide and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95%CI = 1.02-1.46, P=0.03; 1.90; 95%CI = 1.30-2.77, P=0.001; 2.25; 95%CI = 1.43-3.54, P=0.0005 and 2.09; 95%CI = 1.19-3.67, P=0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95%CI = 1.05-1.42, P=0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95%CI = 1.25-2.11, P=0.0003) and IBD (IRR = 10.5; 95%CI = 2.20-50.90, P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide and non-HMW adiponectin, and 0.46 for GLDH indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.
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21.
  • Aleksandrova, Krasimira, et al. (författare)
  • Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into Cancer and nutrition cohort
  • 2012
  • Ingår i: Cancer Research. - Philadelphia, USA : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 72:20, s. 5328-5337
  • Tidskriftsartikel (refereegranskat)abstract
    • Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40-0.76; P-trend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, P-trend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48-1.44, P-trend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56-1.29, P-trend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis. Cancer Res; 72(20); 5328-37. (C) 2012 AACR.
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22.
  • Aleksandrova, Krasimira, et al. (författare)
  • Metabolic syndrome and risks of colon and rectal cancer : the European prospective investigation into cancer and nutrition study.
  • 2011
  • Ingår i: Cancer prevention research (Philadelphia, Pa.). - 1940-6215. ; 4:11, s. 1873-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolic syndrome (MetS) is purportedly related to risk of developing colorectal cancer; however, the association of MetS, as defined according to recent international criteria, and colorectal cancer has not been yet evaluated. In particular, it remains unclear to what extent the MetS components individually account for such an association. We addressed these issues in a nested case-control study that included 1,093 incident cases matched (1:1) to controls by using incidence density sampling. Conditional logistic regression was used to estimate relative risks (RR) and 95% CIs. MetS was defined according to the criteria of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII), the International Diabetes Federation (IDF), and the 2009 harmonized definition. Among individual components, abdominal obesity (RR = 1.51; 95% CI: 1.16-1.96) was associated with colon cancer, whereas abnormal glucose metabolism was associated with both colon (RR = 2.05; 95% CI: 1.57-2.68) and rectal cancer (RR = 2.07; 95% CI: 1.45-2.96). MetS, as defined by each of the definitions, was similarly associated with colon cancer (e.g., RR = 1.91; 95% CI: 1.47-2.42 for MetS by NCEP/ATPIII), whereas MetS by NCEP/ATPIII, but not IDF or harmonized definition, was associated with rectal cancer (RR = 1.45; 95% CI: 1.02-2.06). Overall, these associations were stronger in women than in men. However, the association between MetS and colorectal cancer was accounted for by abdominal obesity and abnormal glucose metabolism such that MetS did not provide risk information beyond these components (likelihood ratio test P = 0.10 for MetS by NCEP/ATPIII). These data suggest that simple assessment of abnormal glucose metabolism and/or abdominal obesity to identify individuals at colorectal cancer risk may have higher clinical utility than applying more complex MetS definitions. Cancer Prev Res; 4(11); 1873-83. ©2011 AACR.
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23.
  • Aleksandrova, Krasimira, et al. (författare)
  • Physical activity, mediating factors and risk of colon cancer : insights into adiposity and circulating biomarkers from the EPIC cohort
  • 2017
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 46:6, s. 1823-1835
  • Tidskriftsartikel (refereegranskat)abstract
    • There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer. We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline. High physical activity was associated with a lower risk of colon cancer: relative risk a parts per thousand91 MET-h/week vs < 91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively. Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.
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24.
  • Aleksandrova, Krasimira, et al. (författare)
  • The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury : data from the European Prospective Investigation into Cancer and Nutrition
  • 2015
  • Ingår i: American Journal of Clinical Nutrition. - : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 102:6, s. 1498-1508
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having >= 4 cups (600mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.
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25.
  • Aleksandrova, Krasimira, et al. (författare)
  • Total and high-molecular-weight adiponectin and risk of colorectal cancer : the European prospective investigation into cancer and nutrition study
  • 2012
  • Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 33:6, s. 1211-1218
  • Tidskriftsartikel (refereegranskat)abstract
    • Adiponectin - an adipose-tissue-derived protein may provide a molecular link between obesity and colorectal cancer (CRC), but evidence from large prospective studies is limited. In particular, no epidemiological study explored high-molecular-weight (HMW) and non-HMW adiponectin fractions in relation to CRC risk, despite they were hypothesised to have differential biological activities, i.e. regulating insulin sensitivity (HMW-adiponectin) versus inflammatory response (non-HMW-adiponectin). In a prospective nested case-control study we investigated whether pre-diagnostic serum concentrations of total, HMW and non-HMW-adiponectin are associated with risk of CRC, independent of obesity and other known CRC risk factors. A total of 1206 incident cases (755 colon, 451 rectal) were matched to 1206 controls using incidence density sampling. In conditional logistic regression, adjusted for dietary and lifestyle factors, total adiponectin and non-HMW-adiponectin concentrations were inversely associated with risk of CRC [relative risk (RR) comparing highest versus lowest quintile = 0.71, 95% confidence interval (CI) = 0.53-0.95, P (trend)=0.03 for total adiponectin and 0.45, 95%CI=0.34-0.61, P (trend)<0.0001 for non-HMW-adiponectin]. HMW-adiponectin concentrations were not associated with CRC risk (RR=0.91, 95%CI=0.68-1.22, P (trend)=0.55). Non-HMW-adiponectin was associated with CRC risk even after adjustment for body mass index and waist circumference (RR=0.39, 95%CI=0.26-0.60, P (trend)<0.0001); whereas the association with total adiponectin was no longer significant (RR=0.81, 95%CI=0.60-1.09, P (trend)=0.23). When stratified by cancer site, non-HMW-adiponectin was inversely associated with both colon and rectal cancer. These findings suggest an important role of the relative proportion of non-HMW-adiponectin in CRC pathogenesis. Future studies are warranted to confirm these results and to elucidate the underlying mechanisms.
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26.
  • Ali, Alaa M. G., et al. (författare)
  • Alcohol Consumption and Survival after a Breast Cancer Diagnosis: A Literature-Based Meta-analysis and Collaborative Analysis of Data for 29,239 Cases
  • 2014
  • Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 23:6, s. 934-945
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. Methods: A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for "moderate drinkers" versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts. Results: We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate postdiagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85-1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73-0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre-or postdiagnosis alcohol consumption is associated with breast cancer-specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer-specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion: There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer-specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer-specific mortality in ER-negative disease. Impact: Considering the totality of the evidence, moderate postdiagnosis alcohol consumption is unlikely to have a major adverse effect on the survival of women with breast cancer. (C) 2014 AACR.
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27.
  • Allen, Naomi E., et al. (författare)
  • A prospective analysis of the association between macronutrient intake and renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition
  • 2009
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:4, s. 982-987
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous case-control studies have suggested that a high intake of animal foods and its associated nutrients are associated with an increased risk of renal cell carcinoma, although data from prospective studies are limited. We report here on the relationship between macronutrient intake and renal cell carcinoma incidence among 435,293 participants enrolled in the European Prospective Investigation into Cancer and Nutrition. Cox proportional hazard models were used to examine the association of dietary intake of fat, protein, carbohydrate, fiber and cholesterol and risk of renal cell carcinoma adjusted for age, sex, center, height, body mass index, physical activity, education, smoking, menopausal status, alcohol and energy intake. During an average 8.8 years of follow-up, 507 renal cell carcinoma cases occurred. Risk of renal cell carcinoma was not associated with macronutrient intake, including nutrients derived from animal sources. Our results indicate that macronutrient intake is not associated with risk of renal cell carcinoma in this cohort of European men and women. (C) 2009 UICC
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28.
  • Allen, Naomi E, et al. (författare)
  • Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC).
  • 2008
  • Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 15:2, s. 485-497
  • Tidskriftsartikel (refereegranskat)abstract
    • Epidemiological data show that reproductive and hormonal factors are involved in the etiology of endometrial cancer, but there is little data on the association with endogenous sex hormone levels. We analyzed the association between prediagnostic serum concentrations of sex steroids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition using a nested case-control design of 247 incident endometrial cancer cases and 481 controls, matched on center, menopausal status, age, variables relating to blood collection, and, for premenopausal women, phase of menstrual cycle. Using conditional regression analysis, endometrial cancer risk among postmenopausal women was positively associated with increasing levels of total testosterone, free testosterone, estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the highest versus lowest tertile were 2.66 (95% confidence interval (CI) 1.50-4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI 1.20-3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98-2.82; P=0.001) for free estradiol. For total and free testosterone, ORs for the highest versus lowest tertile were 1.44 (95% CI 0.88-2.36; P=0.05) and 2.05 (95% CI 1.23-3.42; P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were not associated with risk. Sex hormone-binding globulin was significantly inversely associated with risk (OR for the highest versus lowest tertile was 0.57, 95% CI 0.34-0.95; P=0.004). In premenopausal women, serum sex hormone concentrations were not clearly associated with endometrial cancer risk, but numbers were too small to draw firm conclusions. In conclusion, relatively high blood concentrations of estrogens and free testosterone are associated with an increased endometrial cancer risk in postmenopausal women.
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29.
  • Allen, Naomi E., et al. (författare)
  • Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition
  • 2013
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:3, s. 635-644
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 330%; ptrend = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 367%, ptrend = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed.
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30.
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31.
  • Amundadottir, Laufey, et al. (författare)
  • Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.
  • 2009
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41, s. 986-990
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.
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32.
  • Anantharaman, Devasena, et al. (författare)
  • Combined effects of smoking and HPV16 in oropharyngeal cancer
  • 2016
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:3, s. 752-761
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood.Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multicentre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.
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33.
  • Andersen, Vibeke, et al. (författare)
  • Fibre intake and the development of inflammatory bowel disease : A European prospective multi-centre cohort study (EPIC-IBD)
  • 2018
  • Ingår i: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 12:2, s. 129-136
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn's disease [CD] and ulcerative colitis [UC] in a large European population.Methods: In total, 401 326 participants, aged 20-80 years, were recruited in eight countries in Europe between 1991 and 1998. At baseline, fibre intake [total fibres, fibres from fruit, vegetables and cereals] was recorded using food frequency questionnaires. The cohort was monitored for the development of inflammatory bowel disease. Each case was matched with four controls and odds ratios [ORs] for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed.Results: In total, 104 and 221 participants developed incident CD and UC, respectively. For both CD and UC, there were no statistically significant associations with either quartiles, or trends across quartiles, for total fibre or any of the individual sources. The associations were not affected by adjusting for smoking and energy intake. Stratification according to smoking status showed null findings apart from an inverse association with cereal fibre and CD in non-smokers [Quartile 4 vs 1 OR = 0.12, 95% confidence interval = 0.02-0.75, p = 0.023, OR trend across quartiles = 0.50, 95% confidence interval = 0.29-0.86, p = 0.017].Conclusion: The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD.
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34.
  • Assi, Nada, et al. (författare)
  • A statistical framework to model the meeting-in-the-middle principle using metabolomic data : application to hepatocellular carcinoma in the EPIC study
  • 2015
  • Ingår i: Mutagenesis. - : Oxford University Press (OUP). - 0267-8357 .- 1464-3804. ; 30:6, s. 743-753
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolomics is a potentially powerful tool for identification of biomarkers associated with lifestyle exposures and risk of various diseases. This is the rationale of the 'meeting-in-the-middle' concept, for which an analytical framework was developed in this study. In a nested case-control study on hepatocellular carcinoma (HCC) within the European Prospective Investigation into Cancer and nutrition (EPIC), serum H-1 nuclear magnetic resonance (NMR) spectra (800 MHz) were acquired for 114 cases and 222 matched controls. Through partial least square (PLS) analysis, 21 lifestyle variables (the 'predictors', including information on diet, anthropometry and clinical characteristics) were linked to a set of 285 metabolic variables (the 'responses'). The three resulting scores were related to HCC risk by means of conditional logistic regressions. The first PLS factor was not associated with HCC risk. The second PLS metabolomic factor was positively associated with tyrosine and glucose, and was related to a significantly increased HCC risk with OR = 1.11 (95% CI: 1.02, 1.22, P = 0.02) for a 1SD change in the responses score, and a similar association was found for the corresponding lifestyle component of the factor. The third PLS lifestyle factor was associated with lifetime alcohol consumption, hepatitis and smoking, and had negative loadings on vegetables intake. Its metabolomic counterpart displayed positive loadings on ethanol, glutamate and phenylalanine. These factors were positively and statistically significantly associated with HCC risk, with 1.37 (1.05, 1.79, P = 0.02) and 1.22 (1.04, 1.44, P = 0.01), respectively. Evidence of mediation was found in both the second and third PLS factors, where the metabolomic signals mediated the relation between the lifestyle component and HCC outcome. This study devised a way to bridge lifestyle variables to HCC risk through NMR metabolomics data. This implementation of the 'meeting-in-the-middle' approach finds natural applications in settings characterised by high-dimensional data, increasingly frequent in the omics generation.
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35.
  • Assi, Nada, et al. (författare)
  • Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC
  • 2018
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 27:5, s. 531-540
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites.Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk.Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24-1.96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100% and 24%.Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators.
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36.
  • Assi, Nada, et al. (författare)
  • Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort
  • 2018
  • Ingår i: American Journal of Clinical Nutrition. - : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 108:1, s. 117-126
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors.Objective: In this study, we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Design: Within a nested case-control study of 147 incident HCC cases and 147 matched controls, partial least squares (PLS) analysis related 7 modified healthy lifestyle index (HLI) variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132 targeted serum-measured metabolites and a liver function score. The association between the resulting PLS scores and HCC risk was examined in multivariable conditional logistic regression models, where ORs and 95% CIs were computed.Results: The lifestyle component's PLS score was negatively associated with lifetime alcohol, BMI, smoking, and diabetes, and positively associated with physical activity. Its metabolic counterpart was positively related to the metabolites sphingomyelin (SM) (OH) C14:1, C16:1, and C22:2, and negatively related to glutamate, hexoses, and the diacyl-phosphatidylcholine PC aaC32:1. The lifestyle and metabolomics components were inversely associated with HCC risk, with the ORs for a 1-SD increase in scores equal to 0.53 (95% CI: 0.38, 0.74) and 0.28 (0.18, 0.43), and the associated AUCs equal to 0.64 (0.57, 0.70) and 0.74 (0.69, 0.80), respectively.Conclusions: This study identified a metabolic signature reflecting a healthy lifestyle pattern which was inversely associated with HCC risk. The metabolic profile displayed a stronger association with HCC than did the modified HLI derived from questionnaire data. Measuring a specific panel of metabolites may identify strata of the population at higher risk for HCC and can add substantial discrimination compared with questionnaire data. This trial was registered at clinicaltrials.gov as NCT03356535.
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37.
  • Bakker, Marije F., et al. (författare)
  • Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort
  • 2016
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 103:2, s. 454-464
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.Objective: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.Design: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin, retinol, alpha-tocopherol, gamma-tocopherol, and 454 vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.Results: In quintile 5 compared with quintile 1, alpha-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and beta-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for beta-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).Conclusion: Our results indicate that higher concentrations of plasma beta-carotene and alpha-carotene are associated with lower breast cancer risk of ER tumors.
  •  
38.
  • Balassiano, Karen, et al. (författare)
  • Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)
  • 2011
  • Ingår i: Cancer Letters. - Amsterdam : Elsevier BV. - 1872-7980 .- 0304-3835. ; 311:1, s. 85-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples. A panel of 10 cancer-associated genes (CHRNA3, DOK1, MGMT, RASSF1A, p14ARF, CDH1, MLH1, ALDH2, GNMT and MTHFR) and LINE-1 repetitive elements were included in the analysis and their association with clinicopathological characteristics (sex, age at diagnosis, anatomical sub-site, histological sub-type) was examined. Three out of the 10 genes analyzed exhibited a marked hypermethylation, whereas two genes (ALDH2 and MTHFR) showed significant hypomethylation, in gastric tumors. Among differentially methylated genes, we identified new genes (CHRNA3 and DOK1) as targets of aberrant hypermethylation in GC, suggesting that epigenetic deregulation of these genes and their corresponding cellular pathways may promote the development and progression of GC. We also found that global demethylation of tumor cell genomes occurs in GC, consistent with the notion that abnormal hypermethylation of specific genes occurs concomitantly with genome-wide hypomethylation. Age and gender had no significant influence on methylation states, but an association was observed between LINE-1 and MLH1 methylation levels with histological subtype and anatomical sub-site. This study identifies aberrant methylation patters in specific genes in GC thus providing information that could be exploited as novel biomarkers in clinics and molecular epidemiology of GC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  •  
39.
  • Baltar, Valéria Troncoso, et al. (författare)
  • A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk
  • 2013
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 28:8, s. 677-688
  • Tidskriftsartikel (refereegranskat)abstract
    • The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.
  •  
40.
  • Baltar, Valéria Troncoso, et al. (författare)
  • Smoking, secondhand smoke, and cotinine levels in a subset of EPIC cohort
  • 2011
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:5, s. 869-875
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Several countries are discussing new legislation regarding the ban on smoking in public places, based on the growing evidence of the hazards of secondhand smoke (SHS) exposure. The objective of the present study is to quantitatively assess the relationship between smoking, SHS, and serum cotinine levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: From a study on lung cancer in the EPIC cohort, questionnaire information on smoking was collected at enrolment, and cotinine was measured in serum. Three statistical models were applied by using samples available in a cross-section design: (i) cotinine levels by categories combining smoking and SHS (n = 859); (ii) the effect of hours of passive smoking exposure in nonsmokers only (n = 107); (iii) the effect of the number of cigarettes consumed per day in current smokers only (n = 832). All models were adjusted for country, sex, age, and body mass index. Results: Among nonsmokers, passive smokers presented significant differences in cotinine compared with nonexposed, with a marked (but not significant) difference among former-smokers. A one hour per day increment of SHS gave rise to a significant 2.58 nmol/L (0.45 ng/mL) increase in mean serum cotinine (P < 0.001). In current smokers, a one cigarette per day increment gave rise to a significant 22.44 nmol/L (3.95 ng/mL) increase in cotinine mean (P < 0.001). Conclusions: There is clear evidence that not only tobacco smoking but also involuntary exposure increases cotinine levels. Impact: This study strengthens the evidence for the benefits of a smoking ban in public places.
  •  
41.
  • Bamia, Christina, et al. (författare)
  • Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: Multicentre, prospective cohort study
  • 2015
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136, s. 1899-1908
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2014 UICC. Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% [HR: 0.28; 95% confidence intervals (CIs): 0.16-0.50, p-trend < 0.001]. The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22-0.78, p-trend50.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case-control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (p-trend50.009), but not decaffeinated (p-trend50.45) coffee for which, however, data were available for a fraction of subjects. Results from this multicentre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects.
  •  
42.
  • Bamia, Christina, et al. (författare)
  • Dietary patterns and survival of older Europeans : the EPIC-Elderly Study (European Prospective Investigation into Cancer and Nutrition)
  • 2007
  • Ingår i: Public Health Nutrition. - : Cambridge University Press. - 1368-9800 .- 1475-2727. ; 10:6, s. 590-598
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the association of a posteriori dietary patterns with overall survival of older Europeans.Design and setting: This is a multi-centre cohort study. Cox regression analysis was used to investigate the association of the prevailing, a posteriori-derived, plant-based dietary pattern with all-cause mortality in a population of subjects who were 60 years or older at recruitment to the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort). Analyses controlled for all known potential risk factors.Subjects: In total, 74 607 men and women, 60 years or older at enrolment and without previous coronary heart disease, stroke or cancer, with complete information about dietary intakes and potentially confounding variables, and with known survival status as of December 2003, were included in the analysis.Results: An increase in the score which measures the adherence to the plant-based diet was associated with a lower overall mortality, a one standard deviation increment corresponding to a statistically significant reduction of 14% (95% confidence interval 5–23%). In country-specific analyses the apparent association was stronger in Greece, Spain, Denmark and The Netherlands, and absent in the UK and Germany.Conclusions: Greater adherence to the plant-based diet that was defined a posteriori in this population of European elders is associated with lower all-cause mortality. This dietary score is moderately positively correlated with the Modified Mediterranean Diet Score that has been constructed a priori and was also shown to be beneficial for the survival of the same EPIC-Elderly cohort.
  •  
43.
  • Barrdahl, Myrto, et al. (författare)
  • Post-G WAS gene-environment interplay in breast cancer : results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79 000 women
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:19, s. 5260-5270
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk. We used a nested case-control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls. We performed stratified analyses for both the risk and prognostic factors, testing for heterogeneity for the risk factors, and case-case comparisons for differential associations of polymorphisms by subgroups of the prognostic factors. We analyzed multiplicative interactions between the SNPs and the risk factors. Finally, we also performed a meta-analysis of the interaction ORs from BPC3 and the Breast Cancer Association Consortium. After correction for multiple testing, no significant interaction between the SNPs and the established risk factors in the BPC3 study was found. The meta-analysis showed a suggestive interaction between smoking status and SLC4A7-rs4973768 (P-interaction = 8.84 x 10(-4)) which, although not significant after considering multiple comparison, has a plausible biological explanation. In conclusion, in this study of up to almost 79 000 women we can conclusively exclude any novel major interactions between genome-wide association studies hits and the epidemiologic risk factors taken into consideration, but we propose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC.
  •  
44.
  • Baumeister, Sebastian E., et al. (författare)
  • Association between physical activity and risk of hepatobiliary cancers : A multinational cohort study
  • 2019
  • Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 70:5, s. 885-892
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).Methods: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection).Results: In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38–0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33–0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC.Conclusions: These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity.Lay summary: In a pan-European study of 467,336 men and women, we found that physical activity is associated with a reduced risk of developing liver cancers over the next decade. This risk was independent of other liver cancer risk factors, and did not vary by age, gender, smoking status, body weight, and alcohol consumption.
  •  
45.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
  •  
46.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
  •  
47.
  • Berndt, Sonja, I, et al. (författare)
  • Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
  • 2022
  • Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
  • Tidskriftsartikel (refereegranskat)abstract
    • Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
  •  
48.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
  •  
49.
  • Berndt, Sonja I, et al. (författare)
  • Large-scale fine mapping of the HNF1B locus and prostate cancer risk
  • 2011
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3322-3329
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous genome-wide association studies have identified two independent variants in HNF1B as susceptibility loci for prostate cancer risk. To fine-map common genetic variation in this region, we genotyped 79 single nucleotide polymorphisms (SNPs) in the 17q12 region harboring HNF1B in 10 272 prostate cancer cases and 9123 controls of European ancestry from 10 case-control studies as part of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. Ten SNPs were significantly related to prostate cancer risk at a genome-wide significance level of P < 5 × 10(-8) with the most significant association with rs4430796 (P = 1.62 × 10(-24)). However, risk within this first locus was not entirely explained by rs4430796. Although modestly correlated (r(2)= 0.64), rs7405696 was also associated with risk (P = 9.35 × 10(-23)) even after adjustment for rs4430769 (P = 0.007). As expected, rs11649743 was related to prostate cancer risk (P = 3.54 × 10(-8)); however, the association within this second locus was stronger for rs4794758 (P = 4.95 × 10(-10)), which explained all of the risk observed with rs11649743 when both SNPs were included in the same model (P = 0.32 for rs11649743; P = 0.002 for rs4794758). Sequential conditional analyses indicated that five SNPs (rs4430796, rs7405696, rs4794758, rs1016990 and rs3094509) together comprise the best model for risk in this region. This study demonstrates a complex relationship between variants in the HNF1B region and prostate cancer risk. Further studies are needed to investigate the biological basis of the association of variants in 17q12 with prostate cancer.
  •  
50.
  • Berndt, Sonja I., et al. (författare)
  • Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
  •  
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