| 1. |
- Agudo, Antonio, et al.
(författare)
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Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2013
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 34:6, s. 1244-1250
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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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| 2. |
- Aleksandrova, Krasimira, et al.
(författare)
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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
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 172:4, s. 407-418
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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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| 3. |
- Aleksandrova, Krasimira, et al.
(författare)
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Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into Cancer and nutrition cohort
- 2012
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Ingår i: Cancer Research. - Philadelphia, USA : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 72:20, s. 5328-5337
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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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| 4. |
- Aleksandrova, Krasimira, et al.
(författare)
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Metabolic syndrome and risks of colon and rectal cancer : the European prospective investigation into cancer and nutrition study.
- 2011
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Ingår i: Cancer prevention research (Philadelphia, Pa.). - 1940-6215. ; 4:11, s. 1873-83
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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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| 5. |
- Aleksandrova, Krasimira, et al.
(författare)
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Total and high-molecular-weight adiponectin and risk of colorectal cancer : the European prospective investigation into cancer and nutrition study
- 2012
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 33:6, s. 1211-1218
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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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| 6. |
- Allen, Naomi E., et al.
(författare)
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A prospective analysis of the association between macronutrient intake and renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:4, s. 982-987
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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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| 7. |
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| 8. |
- Baltar, Valéria Troncoso, et al.
(författare)
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A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk
- 2013
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 28:8, s. 677-688
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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.
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| 9. |
- Baltar, Valéria Troncoso, et al.
(författare)
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Smoking, secondhand smoke, and cotinine levels in a subset of EPIC cohort
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:5, s. 869-875
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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.
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| 10. |
- Boffetta, Paolo, et al.
(författare)
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Fruit and vegetable intake and overall cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).
- 2010
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102:8, s. 529-537
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is widely believed that cancer can be prevented by high intake of fruits and vegetables. However, inconsistent results from many studies have not been able to conclusively establish an inverse association between fruit and vegetable intake and overall cancer risk. METHODS: We conducted a prospective analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to assess relationships between intake of total fruits, total vegetables, and total fruits and vegetables combined and cancer risk during 1992-2000. Detailed information on the dietary habit and lifestyle variables of the cohort was obtained. Cancer incidence and mortality data were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models. Analyses were also conducted for cancers associated with tobacco and alcohol after stratification for tobacco smoking and alcohol drinking. RESULTS: Of the initial 142 605 men and 335 873 women included in the study, 9604 men and 21 000 women were identified with cancer after a median follow-up of 8.7 years. The crude cancer incidence rates were 7.9 per 1000 person-years in men and 7.1 per 1000 person-years in women. Associations between reduced cancer risk and increased intake of total fruits and vegetables combined and total vegetables for the entire cohort were similar (200 g/d increased intake of fruits and vegetables combined, HR = 0.97, 95% CI = 0.96 to 0.99; 100 g/d increased intake of total vegetables, HR = 0.98, 95% CI = 0.97 to 0.99); intake of fruits showed a weaker inverse association (100 g/d increased intake of total fruits, HR = 0.99, 95% CI = 0.98 to 1.00). The reduced risk of cancer associated with high vegetable intake was restricted to women (HR = 0.98, 95% CI = 0.97 to 0.99). Stratification by alcohol intake suggested a stronger reduction in risk in heavy drinkers and was confined to cancers caused by smoking and alcohol. CONCLUSIONS: A very small inverse association between intake of total fruits and vegetables and cancer risk was observed in this study. Given the small magnitude of the observed associations, caution should be applied in their interpretation.
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