Daily alcohol consumption and sickness absence in the GAZEL cohort.

Background: : Previous studies that examined the association between daily alcohol consumption and sickness absences (SA) were mostly retrospective and did not take into account the characteristics of SA. : A total of 9907 daily drinkers (8442 men and 1465 women) of the GAZEL prospective cohort were included. Daily alcohol consumption over the three previous years was self-reported at baseline and categorized as low, moderate, high or very high risk according to the World Health Organization. Duration of SA (short: ≤7 days; moderate: 8-28; long: >28) was collected from administrative records as well as causes for long SA. Negative binomial regression models were used to estimate Risk Ratios of SA according to alcohol consumption with low-risk category as reference. : Duration of follow-up (in years) for SA was 8.4 ± 3.7 in men and 11.2 ± 5.4 in women. Increasing alcohol consumption predicted increasing risk of SA with a dose-response relationship ( P < 0.01 for men; P = 0.01 for women). In men, strength of this association increased with SA duration [e.g. RRs from 1.41 (95% CI: 1.12-1.79) to 2.12 (95% CI: 1.49-3.00) in the very high-risk category, for short and long SA, respectively]. In men, even a moderate consumption predicted increased risk of SA whatever their duration (RR = 1.15; 95% CI: 1.07-1.23). In women, a moderate consumption predicted only long SA (RR = 1.22; 95% CI: 1.00-1.50). Daily alcohol consumption was associated with almost all causes of long SA in men, and with respiratory diseases, digestive diseases and injury in women. : We found a dose-response relationship between daily alcohol consumption and the risk of SA. Even moderate consumption could increase this risk, particularly in men.

Heme Iron Intake, Dietary Antioxidant Capacity, and Risk of Colorectal Adenomas in a Large Cohort Study of French Women.

BACKGROUND: Nitrosylated and non-nitrosylated heme iron from red processed and nonprocessed meat have been associated with increased colorectal carcinogenesis. Mechanisms include oxidative processes. It has been hypothesized that dietary antioxidants could counteract the effects of heme iron. We investigated the relationships between heme iron intake and the risk of colorectal adenomas, and a potential interaction with the dietary antioxidant capacity, in the E3N prospective cohort study. METHODS: The study included 17,397 women, who underwent at least one colonoscopy. Among them, 1,409 were diagnosed with at least one first colorectal adenoma during the 103,253 person-years of follow-up. Dietary intake was measured by a semiquantitative food history questionnaire. HR estimates and 95% confidence intervals (CI) were obtained from Cox proportional hazards models, adjusted for potential confounders. RESULTS: Heme iron intake was positively associated with colorectal and colon adenoma risks [HR for the fourth vs. first quartile: HR4 = 1.36 (1.13-1.65), Ptrend = 0.001 and HR4 = 1.49; 95% CI, 1.19-1.87; Ptrend = 0.0003, respectively]. Nonnitrosylated and nitrosylated heme iron intakes were, respectively, associated with advanced distal and proximal adenoma risks. There was a dose-effect relationship between the heme iron to total dietary antioxidant capacity ratio and colorectal adenoma risk. CONCLUSION: In this prospective cohort study, the association between heme iron and colorectal adenoma risk was found to depend on site, nitrosylation or not, and the ratio with the NEAC. IMPACT: These results emphasize the need for a global assessment of diet when considering nutritional prevention of colorectal carcinogenesis. Cancer Epidemiol Biomarkers Prev; 25(4); 640-7. ©2016 AACR.

More than Light Alcohol Consumption Predicts Early Cessation from Employment in French Middle-Aged Men.

AIMS: To investigate the association between alcohol consumption and different causes of work cessation and estimate the loss of occupational activity among high consumers compared with low consumers. METHODS: From the prospective study of men employed in the French gas and electric company, 8442 men during a median follow-up of 8.4 years reported on their alcohol consumption. Information on work cessation was collected from the company administrative records. Hazard Ratios (HRs) by cause of work cessation (death, disability, retirement before or after age 55) were estimated using a competing risk method. RESULTS: An increasing quantity of daily alcohol consumption was associated with an increased risk of death, disability and retirement before age 55 (P trend ≤ 0.01, = 0.03 and ≤ 0.01, respectively), but not of retirement after age 55 (P trend = 0.56). Moreover, compared with low consumption, moderate, high or very high daily intakes were associated with an increased risk of early work cessation (combination of the three causes: death, disability and retirement before age 55) (HR = 1.14, 95% confidence interval (CI) = 1.05-1.25; HR = 1.23, 95% CI = 1.12-1.35 and HR = 1.49, 95% CI = 1.15-1.92 respectively). Between ages 50 and 60, we estimated that high or very high consumers could gain 6.04 months of occupational activity if they drank like low consumers. CONCLUSIONS: Our results provide evidence of a dose-effect relationship between alcohol consumption and early work cessation.

Colonoscopy reduced distal colorectal cancer risk and excess cancer risk associated with family history.

PURPOSE: Colonoscopy efficacy at preventing proximal colorectal cancer (CRC) is questioned, and little is known about efficacy in high-risk versus medium-risk populations. We investigated the relationship between colonoscopy screening, family history of colorectal cancer (FHCC), and CRC risk by site. METHODS: Among 92,078 women of the E3N prospective cohort, 692 CRCs have been diagnosed after a median follow-up of 15.4 years. Cox proportional hazard models estimated adjusted hazards ratios according to subsites of cancer and FHCC. RESULTS: A personal history of colonoscopy (PHC; n = 37,470) was associated with decreased rectal and distal colon cancer risks (hazard ratio (HR) = 0.57; 95% Confidence Interval (CI) = 0.42-0.78 and HR = 0.37; 95% CI = 0.26-0.52, respectively), but not proximal colon cancer risk (HR = 0.87; 95% CI = 0.64-1.18). In women with no prior colonoscopy, those with FHCC had a 80% higher CRC risk than those without FHCC. In women with previous colonoscopy, CRC risk was similar in women with and without FHCC (p for interaction = 0.04). CONCLUSIONS: Results showed colonoscopy ability to prevent distal cancers, but not proximal cancers in women. Colonoscopy screening also reduced the excess risk of women with FHCC to that of women with no FHCC.

Erythrocyte membrane phospholipid fatty acid concentrations and risk of colorectal adenomas: a case-control nested in the French E3N-EPIC cohort study.

BACKGROUND: Although dietary fatty acids may influence colorectal carcinogenesis, few studies have examined the association with adenoma risk. We assessed the association between biomarkers of dietary fatty acids or metabolism of fatty acids and the risk of colorectal adenomas in a nested case-control study from the French E3N-EPIC cohort. METHODS: Among 13,106 women without prevalent cancer who completed the diet history questionnaire and who provided blood samples, 328 cases of adenomatous polyp were identified during an average of 6.6-year follow-up and randomly matched to 619 polyp-free colonoscopy controls. Erythrocyte membrane phospholipid fatty acid concentrations were determined by gas chromatography. Adjusted ORs for risk of colorectal adenomas with increasing concentrations of fatty acids were calculated using conditional logistic regression, separately for advanced and nonadvanced adenomas. RESULTS: Associations were stronger with advanced than nonadvanced adenomas. High concentration of pentadecanoate plus heptadecanoate acids were inversely associated with the risk of advanced adenomas [highest vs. lowest tertile: OR(T3vsT1) = 0.40 (95% confidence interval (CI) 0.20-0.79); P(trend) = 0.009]. Oleic acid was associated with an increased risk of advanced adenomas [OR(T3vsT1) = 2.32 (1.16-4.64); P(trend) = 0.018]. Some polyunsaturated fatty acids were associated with the risk of advanced adenomas, either positively for di-homo-γ-linolenate [OR(T3vsT1) = 2.07 (1.15-3.72); P(trend) = 0.013], or negatively for eicosapentaenoic and docosahexaenoic acids [OR(T3vsT1) = 0.50 (0.27-0.93); P(trend) = 0.044 and OR(T3vsT1) = 0.50 (0.26-0.96); P(trend) = 0.028, respectively]. CONCLUSION: A specific erythrocyte membrane phospholipid fatty acid profile, presumably reflecting both a complex dietary pattern and altered fatty acid metabolism, is associated with advanced colorectal adenoma risk. IMPACT: Adenomas could be a target for primary prevention of colorectal cancer, using interventional strategy based on lipidomic profile of patients.

Mediterranean diet and colorectal cancer risk: results from a European cohort.

The authors investigated the association of adherence to Mediterranean diet with colorectal cancer (CRC) risk in the European Prospective Investigation into Cancer and nutrition study. Adherence to Mediterranean diet was expressed through two 10-unit scales, the Modified Mediterranean diet score (MMDS) and the Centre-Specific MMDS (CSMMDS). Both scales share the same dietary components but differ in the cut-off values that were used for these components in the construction of the scales. Adjusted hazard ratios (HR) for the associations of these scales with CRC incidence were estimated. After 5,296,617 person-years of follow-up, 4,355 incident CRC cases were identified. A decreased risk of CRC, of 8 and 11 % was estimated when comparing the highest (scores 6-9) with the lowest (scores 0-3) adherence to CSMMDS and MMDS respectively. For MMDS the HR was 0.89 (95 % confidence interval (CI): 0.80, 0.99). A 2-unit increment in either Mediterranean scale was associated with a borderline statistically significant 3 to 4 % reduction in CRC risk (HR for MMDS: 0.96; 95 % CI: 0.92, 1.00). These associations were somewhat more evident, among women, were mainly manifested for colon cancer risk and their magnitude was not altered when alcohol was excluded from MMDS. These findings suggest that following a Mediterranean diet may have a modest beneficial effect on CRC risk.

Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiveness. Therefore, we examined the relation between fruit and vegetable consumption and the risk of aggressive and non-aggressive UCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: After 8.9 years of follow-up, 947UCC were diagnosed among 468,656 EPIC participants. Of these, 421 could be classified as aggressive UCC and 433 as non-aggressive UCC cases. At recruitment, fruit and vegetable consumption was assessed by validated dietary questionnaires. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for smoking status, duration and intensity of smoking, and energy intake. RESULTS: Total consumption of fruits and vegetables was not associated with aggressive UCC nor with non-aggressive UCC. A 25 g/day increase in leafy vegetables and grapes consumption was associated with a reduced risk of non-aggressive UCC (hazard ratio (HR) 0.88; 95%confidence interval (CI) 0.78-1.00 and HR 0.87; 95%CI 0.77-0.98, respectively), while the intake of root vegetables was inversely associated with risk of aggressive UCC (HR 0.87; 95%CI 0.77-0.98). CONCLUSION: Our study did not confirm a protective effect of total fruit and/or vegetable consumption on aggressive or non-aggressive UCC. High consumption of certain types of vegetables and of fruits may reduce the risk of aggressive or non-aggressive UCC; however chance findings cannot be excluded.

Menopausal hormone therapy and risks of colorectal adenomas and cancers in the French E3N prospective cohort: true associations or bias?

Menopausal hormone therapy (MHT) use has been quite consistently associated with a decreased colorectal cancer risk; however, data regarding adenomas, types of MHT, or tumour site are limited. We investigated associations between MHT use and colorectal adenoma and cancer risks within the prospective E3N cohort study. In the adenoma study, we analyzed the 13,402 postmenopausal women who underwent a colonoscopy during follow-up (1993-2002), including 1,109 who were diagnosed a first colorectal adenoma. In the cancer study, 525 out of 77,375 postmenopausal women developed a colorectal cancer as the first malignant tumour during follow-up (1992-2008). Ever use of MHT was not significantly associated with colorectal adenoma risk [Hazard Ratio (HR) = 1.13, 95 % Confidence Interval (CI) = 0.99, 1.29], nor with colorectal cancer risk (HR = 0.86, 95 % CI = 0.71, 1.04). However, ever use of estrogens alone was associated with risks of colorectal adenoma and cancer in opposite directions (HR = 1.22, 95 % CI = 1.05, 1.41 and HR = 0.72, 95 % CI = 0.56, 0.94 respectively). Associations were strongest for non-advanced, and for left colon adenomas. Duration, recency of use, type of progestagen or route of estrogen administration were not associated with colorectal tumour risk, nor was the use of estrogen-progestagen MHT. The association between estrogens alone and colorectal cancer risk was only observed in women with previous colonoscopy(ies), but the P value of the interaction test between estrogens alone use and history of colonoscopy was 0.06. Our data suggest a complex relationship between MHT use, colorectal tumour risk and screening strategies, which deserves further investigations in other settings.

Biomarkers of oxidative stress and risk of developing colorectal cancer: a cohort-nested case-control study in the European Prospective Investigation Into Cancer and Nutrition.

Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992-2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRR(adj)) = 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRR(adj) = 1.89, 95% CI: 1.06, 3.36) and distal (IRR(adj) = 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRR(adj) = 1.69, 95% CI: 1.05, 2.72). When results were stratified by tertile of follow-up time, the association remained significant only in participants with less than 2.63 years of follow-up (IRR(adj) = 2.28, 95% CI: 1.78, 2.94; P-heterogeneity < 0.01). FRAP was not associated with CRC risk. In conclusion, prediagnostic serum ROM levels were associated with increased risk of CRC. However, this association was seen only in subjects with relatively short follow-up, suggesting that the association results from production of reactive oxygen species by preclinical tumors.

Dietary intake of heme iron and risk of gastric cancer in the European prospective investigation into cancer and nutrition study.

Even though recent studies suggest that a high intake of heme iron is associated with several types of cancer, epidemiological studies in relation to gastric cancer (GC) are lacking. Our previous results show a positive association between red and processed meat and non cardia gastric cancer, especially in Helicobacter pylori infected subjects. The aim of the study is to investigate the association between heme iron intake and GC risk in the European prospective investigation into cancer and nutrition (EURGAST-EPIC). Dietary intake was assessed by validated center-specific questionnaires. Heme iron was calculated as a type-specific percentage of the total iron content in meat intake, derived from the literature. Antibodies of H. pylori infection and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control study within the cohort. The study included 481,419 individuals and 444 incident cases of GC that occurred during an average of 8.7 years of followup. We observed a statistically significant association between heme iron intake and GC risk (HR 1.13 95% CI: 1.01-1.26 for a doubling of intake) adjusted by sex, age, BMI, education level, tobacco smoking and energy intake. The positive association between heme iron and the risk of GC was statistically significant in subjects with plasma vitamin C <39 mmol/l only (log2 HR 1.54 95% CI (1.01-2.35). We found a positive association between heme iron intake and gastric cancer risk.

Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location.

Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational level and CRC. We studied data from 400,510 participants in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,447 developed CRC (colon: 1,551, rectum: 896, mean follow-up 8.3 years). Cox proportional hazard regression analysis stratified by age, gender and center, and adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Relative indices of inequality (RII) for education were estimated using Cox regression models. We conducted separate analyses for tumor location, gender and geographical region. Compared with participants with college/university education, participants with vocational secondary education or less had a nonsignificantly lower risk of developing CRC. When further stratified for tumor location, adjusted risk estimates for the proximal colon were statistically significant for primary education or less (HR 0.73, 95%CI 0.57-0.94) and for vocational secondary education (HR 0.76, 95%CI 0.58-0.98). The inverse association between low education and CRC risk was particularly found in women and Southern Europe. These associations were statistically significant for CRC, for colon cancer and for proximal colon cancer. In conclusion, CRC risk, especially in the proximal colon, is lower in subjects with a lower educational level compared to those with a higher educational level. This association is most pronounced in women and Southern Europe.

Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study.

A high intake of dietary antioxidant compounds has been hypothesized to be an appropriate strategy to reduce gastric cancer (GC) development. We investigated the effect of dietary total antioxidant capacity (TAC) in relation to GC in the European Prospective Investigation into Cancer (EPIC) study including 23 centers in 10 European countries. A total of 521,457 subjects (153,447 men) aged mostly 35-70 years old, were recruited largely between 1992 and 1998. Ferric reducing antioxidant potential (FRAP) and total radical-trapping antioxidant parameter (TRAP), measuring reducing and chain-breaking antioxidant capacity were used to measure dietary TAC from plant foods. Dietary antioxidant intake is associated with a reduction in the risk of GC for both FRAP (adjusted HR 0.66; 95%CI (0.46-0.95) and TRAP (adjusted HR 0.61; 95%CI (0.43-0.87) (highest vs. lowest quintile). The association was observed for both cardia and noncardia cancers. A clear effect was observed in smokers with a significant reduction in GC risk for the fifth quintile of intake for both assays (highest vs. lowest quintile: adjusted HR 0.41; 95%CI (0.22-0.76) p for trend <0.001 for FRAP; adjusted HR 0.52; 95%CI (0.28-0.97) p for trend <0.001 for TRAP) but not in nonsmokers. In former smokers, the association with FRAP intake was statistically significant (highest vs. lowest quintile: adjusted HR 0.4; 95%CI (0.21-0.75) p < 0.05); no association was observed for TRAP. Dietary antioxidant capacity intake from different sources of plant foods is associated with a reduction in the risk of GC.

Fruit and vegetable consumption and prospective weight change in participants of the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home, and Obesity study.

BACKGROUND: Fruit and vegetable consumption might prevent weight gain through their low energy density and high dietary fiber content. OBJECTIVE: We assessed the association between the baseline consumption of fruit and vegetables and weight change in participants from 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition study. DESIGN: Diet was assessed at baseline in 373,803 participants by using country-specific validated questionnaires. Weight was measured at baseline and self-reported at follow-up in most centers. Associations between baseline fruit and vegetable intakes (per 100 g/d) and weight change (g/y) after a mean follow-up of 5 y were assessed by using linear mixed-models, with age, sex, total energy intake, and other potential confounders controlled for. RESULTS: After exclusion of subjects with chronic diseases at baseline and subjects who were likely to misreport energy intakes, baseline fruit and vegetable intakes were not associated with weight change overall. However, baseline fruit and vegetable intakes were inversely associated with weight change in men and women who quit smoking during follow-up. We observed weak positive associations between vegetable intake and weight change in women who were overweight, were former smokers, or had high prudent dietary pattern scores and weak inverse associations between fruit intake and weight change in women who were >50 y of age, were of normal weight, were never smokers, or had low prudent dietary pattern scores. CONCLUSIONS: In this large study, higher baseline fruit and vegetable intakes, while maintaining total energy intakes constant, did not substantially influence midterm weight change overall but could help to reduce risk of weight gain in persons who stop smoking. The interactions observed in women deserve additional attention.

Alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: Gastric cancer (GC) is the second leading cause of cancer death worldwide. The association between alcohol consumption and GC has been investigated in numerous epidemiologic studies with inconsistent results. OBJECTIVE: We evaluated the association between alcohol consumption and GC risk. DESIGN: We conducted a prospective analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which included 444 cases of first primary gastric adenocarcinoma. HRs and 95% CIs for GC were estimated by using multivariable Cox proportional hazards regression for consumption of pure ethanol in grams per day, with stratification by smoking status, anatomic subsite (cardia, noncardia), and histologic subtype (diffuse, intestinal). In a subset of participants, results were further adjusted for baseline Helicobacter pylori serostatus. RESULTS: Heavy (compared with very light) alcohol consumption (≥60 compared with 0.1-4.9 g/d) at baseline was positively associated with GC risk (HR: 1.65; 95% CI: 1.06, 2.58), whereas lower consumption amounts (<60 g/d) were not. When we analyzed GC risk by type of alcoholic beverage, there was a positive association for beer (≥30 g/d; HR: 1.75; 95% CI: 1.13, 2.73) but not for wine or liquor. Associations were primarily observed at the highest amounts of drinking in men and limited to noncardia subsite and intestinal histology; no statistically significant linear dose-response trends with GC risk were observed. CONCLUSION: Heavy (but not light or moderate) consumption of alcohol at baseline (mainly from beer) is associated with intestinal-type noncardia GC risk in men from the EPIC cohort.

Risks of colon and rectal adenomas are differentially associated with anthropometry throughout life: the French E3N prospective cohort.

BACKGROUND: Associations between adult anthropometry and risk of colorectal neoplasms are well established. However, whereas body mass in infancy and childhood has been associated with risk of some cancers, little is known about potential associations with colorectal neoplasms. The authors investigated associations between colorectal adenoma risk and lifetime anthropometry, in an attempt to better understand the relationships between anthropometric features and colorectal carcinogenesis. METHODS: Among the 17 391 women of the French E3N cohort who underwent a colonoscopy during follow-up (1993-2002), 1408 developed a first colorectal adenoma. Associations were estimated with Cox multivariate proportional hazard regression models. RESULTS: Left colon adenoma risk was associated with high birth weight [hazard ratio (HR) high vs median = 1.21; 95% confidence interval (95% CI): 1.00-1.47, P(trend) = 0.03] and large adult body shape (HR = 1.28; 95% CI: 1.04-1.56, P(trend) = 0.02). A large versus small body shape at age 8 years and at menarche were associated with a decreased rectal adenoma risk [HR = 0.68; 95% CI: 0.49-0.95, P(trend) = 0.01 and 0.73 (0.53-1.01), P(trend) = 0.05, respectively]. Except for a positive association with large vs median birth weight, no anthropometric characteristic was associated with right colon adenoma risk. Associations did not differ between advanced and non-advanced adenomas. CONCLUSIONS: These findings suggest that early life events may influence early stages of colorectal carcinogenesis and add to the evidence of differential pathways of carcinogenesis in the right colon, left colon and rectum.

Metabolic syndrome and risks of colon and rectal cancer: the European prospective investigation into cancer and nutrition study.

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.

A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.

Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (± 1 year), date (± 1 year) and time (± 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate ≤ 5, 5-10, 10-15 (reference), 15-20, and > 20 nmol/L were 1.58 (95% CI=0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR=1.17, 95% CI=1.00-1.38) but not in women (OR=0.91, 95% CI=0.78-1.07; p for heterogeneity <0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.

Cigarette smoking and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND & AIMS: There has been consistent evidence for a relationship between smoking and colorectal cancer (CRC), although it is not clear whether the colon or rectum is more sensitive to the effects of smoking. We investigated the relationships between cigarette smoking and risk of CRC and tumor location. METHODS: We analyzed data from 465,879 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study; 2741 developed CRC during the follow-up period (mean, 8.7 years). Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The risk of colon carcinoma was increased among ever smokers (HR, 1.18; 95% CI, 1.06-1.32) and former cigarette smokers (HR, 1.21; 95% CI, 1.08-1.36), compared with never smokers; the increased risk for current smokers was of borderline significance (HR, 1.13; 95% CI, 0.98-1.31). When stratified for tumor location, the risk of proximal colon cancer was increased for former (HR, 1.25; 95% CI, 1.04-1.50) and current smokers (HR, 1.31; 95% CI, 1.06-1.64), but the risks for cancers in the distal colon or rectum were not. Subsite analyses showed a nonsignificant difference between the proximal and distal colon (P = .45) for former smokers and a significant difference for current smokers (P = .02). For smokers who had stopped smoking for at least 20 years, the risk of developing colon cancer was similar to that of never smokers. CONCLUSIONS: Ever smokers have an increased risk of colon cancer, which appeared to be more pronounced in the proximal than the distal colon location.

Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of colorectal cancer risk.

BACKGROUND: B-vitamins are essential for one-carbon metabolism and have been linked to colorectal cancer. Although associations with folate have frequently been studied, studies on other plasma vitamins B2, B6, and B12 and colorectal cancer are scarce or inconclusive. METHODS: We carried out a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, including 1,365 incident colorectal cancer cases and 2,319 controls matched for study center, age, and sex. We measured the sum of B2 species riboflavin and flavin mononucleotide, and the sum of B6 species pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid as indicators for vitamin B2 and B6 status, as well as vitamin B12 in plasma samples collected at baseline. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for colorectal cancer were estimated using conditional logistic regression, adjusted for smoking, education, physical activity, body mass index, alcohol consumption, and intakes of fiber and red and processed meat. RESULTS: The relative risks comparing highest to lowest quintile were 0.71 [95% confidence interval (95% CI), 0.56-0.91; P(trend) = 0.02] for vitamin B2, 0.68 (95% CI, 0.53-0.87; P(trend) <0.001) for vitamin B6, and 1.02 (95% CI, 0.80-1.29; P(trend) = 0.19) for vitamin B12. The associations for vitamin B6 were stronger in males who consumed ≥30 g alcohol/day. The polymorphisms were not associated with colorectal cancer. CONCLUSIONS: Higher plasma concentrations of vitamins B2 and B6 are associated with a lower colorectal cancer risk. IMPACT: This European population-based study is the first to indicate that vitamin B2 is inversely associated with colorectal cancer, and is in agreement with previously suggested inverse associations of vitamin B6 with colorectal cancer.

Anthropometric factors in adulthood and risk of colorectal adenomas: The French E3N-EPIC prospective cohort.

Anthropometric factors have been associated with colorectal cancer and adenomas but with conflicting results in women or regarding adenoma characteristics. The authors aimed to explore associations between anthropometric factors (height, weight, body mass index, waist and hip circumferences, and weight changes) and adenoma risk. They analyzed the 17,391 women of the French Etude épidémiologique des femmes de la Mutuelle Générale de l'Education Nationale (E3N)-European Prospective Investigation into Cancer and Nutrition (EPIC) cohort who underwent a colonoscopy during follow-up (1993-2002), including 1,408 who developed a first colorectal adenoma. In Cox multivariate proportional hazard regression models, obesity was associated with an increased colorectal adenoma risk (hazard ratio = 1.53, 95% confidence interval: 1.21, 1.94). This association was restricted to left colon adenomas (P(homogeneity) = 0.05 and 0.01 for colon vs. rectum and right vs. left colon, respectively), with a dose-effect relation observed from 22 kg/m². A high waist circumference was also associated with left colon adenoma risk (hazard ratio = 1.81, 95% confidence interval: 1.36, 2.41). Mean weight gain over 0.5 kg/year was associated with a 23% increased colorectal adenoma risk. Associations did not differ between advanced and nonadvanced adenomas. In conclusion, study findings suggest that obesity and weight gain are associated with early colorectal carcinogenesis in women, and specifically regarding the distal colon.