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1.
  • 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. ; 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 casecontrol 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 1.031.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR 1.60, CI 1.162.21) and intestinal histological subtype (OR 1.82, CI 1.272.62). 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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2.
  • 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. - American Society of Clinical Oncology. - 1527-7755.
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSEOur 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). METHODSThe 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.ResultsThe 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. CONCLUSIONUsing 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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3.
  • Agudo, Antonio, et al. (författare)
  • Inflammatory potential of the diet and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
  • 2018
  • Ingår i: American Journal of Clinical Nutrition. - American Society for Clinical Nutrition. - 0002-9165. ; 107:4, s. 607-616
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation. Objective We assessed the association between the inflammatory potential of the diet and the risk of gastric carcinoma, overall and for the 2 major subsites: cardia cancers and noncardia cancers. Design A total of 476,160 subjects (30% men, 70% women) from the European Investigation into Cancer and Nutrition (EPIC) study were followed for 14 y, during which 913 incident cases of gastric carcinoma were identified, including 236 located in the cardia, 341 in the distal part of the stomach (noncardia), and 336 with overlapping or unknown tumor site. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated with the use of 28 dietary components and their corresponding inflammatory scores. The association between the ISD and gastric cancer risk was estimated by HRs and 95% CIs calculated by multivariate Cox regression models adjusted for confounders. Results The inflammatory potential of the diet was associated with an increased risk of gastric cancer. The HR (95% CI) for each increase in 1 SD of the ISD were 1.25 (1.12, 1.39) for all gastric cancers, 1.30 (1.06, 1.59) for cardia cancers, and 1.07 (0.89, 1.28) for noncardia cancers. The corresponding values for the highest compared with the lowest quartiles of the ISD were 1.66 (1.26, 2.20), 1.94 (1.14, 3.30), and 1.07 (0.70, 1.70), respectively. Conclusions Our results suggest that low-grade chronic inflammation induced by the diet may be associated with gastric cancer risk. This pattern seems to be more consistent for gastric carcinomas located in the cardia than for those located in the distal stomach. This study is listed on the ISRCTN registry as ISRCTN12136108.
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4.
  • 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 (BMC). - 1741-7015. ; 12
  • 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.
5.
  • Aleksandrova, Krasimira, et al. (författare)
  • Inflammatory and Metabolic Biomarkers and Risk of Liver and Biliary Tract Cancer
  • 2014
  • Ingår i: Hepatology. - John Wiley and Sons Inc.. - 1527-3350. ; 60:3, s. 858-871
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however, there are 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), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. 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, and 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 (CIs) were 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-HMWadiponectin 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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8.
  • 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. - John Wiley and Sons Inc.. - 0020-7136. ; 136:8, s. 1899-1908
  • Tidskriftsartikel (refereegranskat)abstract
    • 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-trend=0.003). 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-trend=0.009), but not decaffeinated (p-trend=0.45) 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.
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9.
  • Barrdahl, Myrto, et al. (författare)
  • A comprehensive analysis of polymorphic variants in steroid hormone and insulin-like growth factor-1 metabolism and risk of in situ breast cancer : Results from the Breast and Prostate Cancer Cohort Consortium
  • 2018
  • Ingår i: International Journal of Cancer. - John Wiley and Sons Inc.. - 0020-7136. ; 142:6, s. 1182-1188
  • Tidskriftsartikel (refereegranskat)abstract
    • We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and insulin-like growth factor 1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was carried out using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer cases from the Breast and Prostate Cancer Cohort Consortium (BPC3). Three SNPs showed at least one nominally significant association in homozygous minor versus homozygous major models. ACVR2A-rs2382112 (ORhom=3.05, 95%CI=1.72-5.44, Phom=1.47 × 10-4), MAST2-rs12124649 (ORhom=1.73, 95% CI =1.18-2.54, Phom=5.24 × 10-3), and INSR-rs10500204 (ORhom=1.96, 95% CI=1.44-2.67, Phom=1.68 × 10-5) were associated with increased risk of BCIS; however, only the latter association was significant after correcting for multiple testing. Furthermore, INSR-rs10500204 was more strongly associated with the risk of BCIS than invasive disease in case-only analyses using the homozygous minor versus homozygous major model (ORhom=1.78, 95% CI=1.30-2.44, Phom=3.23 × 10-4). The SNP INSR-rs10500204 is located in an intron of the INSR gene and is likely to affect binding of the promyelocytic leukemia (PML) protein. The PML gene is known as a tumor suppressor and growth regulator in cancer. However, it is not clear on what pathway the A-allele of rs10500204 could operate to influence the binding of the protein. Hence, functional studies are warranted to investigate this further.
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10.
  • Bešević, Jelena, et al. (författare)
  • Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study.
  • 2015
  • Ingår i: British Journal of Cancer. - Nature Publishing Group. - 1532-1827. ; 113:11, s. 1622-1631
  • Tidskriftsartikel (refereegranskat)abstract
    • Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521 330 total participants (approximately 370 000 women) aged 25-70 years at recruitment from 1992 to 2000.
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