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Atlanta, GA, United States

Stevens V.L.,Epidemiology Research Program | Stevens V.L.,Epidemiology Research | McCullough M.L.,Epidemiology Research Program | Sun J.,Epidemiology Research Program | And 3 more authors.
Gastroenterology | Year: 2011

Background & Aims: Folate intake has been inversely associated with colorectal cancer risk in several prospective epidemiologic studies. However, no study fully assessed the influence of the high levels of folate that are frequently consumed in the United States as a result of mandatory folate fortification, which was fully implemented in 1998, and the recent increase in use of folate-containing supplements. There is evidence that consumption of high levels of folic acid, the form of folate used for fortification and in supplements, has different effects on biochemical pathways than natural folates and might promote carcinogenesis. Methods: We investigated the association between folate intake and colorectal cancer among 43,512 men and 56,011 women in the Cancer Prevention Study II (CPS-II) Nutrition Cohort; 1023 were diagnosed with colorectal cancer between 1999 and 2007, a period entirely after folate fortification began. Cox proportional hazards regression was used to calculate multivariate hazards ratios (RR) and 95% confidence interval (CI). Results: Intake of high levels of natural folate (RR Q5vsQ1 = 0.86; 95% CI: 0.701.06; P trend =.12) or folic acid (RR Q5vsQ1 = 0.84; 95% CI: 0.681.03; P trend =.06) were not significantly associated with risk of colorectal cancer. Total folate intake was significantly associated with lower risk (RR Q5vsQ1 = 0.81; 95% CI: 0.660.99; P trend =.047). Conclusions: Intake of high levels of total folate reduces risk of colorectal cancer; there is no evidence that dietary fortification or supplementation with this vitamin increases colorectal cancer risk. © 2011 AGA Institute.

Saccone N.L.,University of Washington | Saccone N.L.,Roche Holding AG | Culverhouse R.C.,University of Washington | Schwantes-An T.,University of Washington | And 69 more authors.
PLoS Genetics | Year: 2010

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a metaanalysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-perday, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10-35 and <10-8 respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10-6). In models adjusting for cigarettes-perday, we confirm the association between rs16969968 and lung cancer (p<10-20) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue.

Stevens V.L.,Epidemiology Research | McCullough M.L.,Epidemiology Research | Sun J.,Epidemiology Research | Gapstur S.M.,Epidemiology Research
American Journal of Clinical Nutrition | Year: 2010

Background: Epidemiologic studies of the association of folate intake with breast cancer risk have been inconclusive, and few have investigated how related nutrients modify this association. Objective: We investigated the association of dietary (food folate plus folic acid from fortification) and total folate (food folate, folic acid from fortification, and folic acid from supplements), vitamin B-6, vitamin B-12, methionine, and alcohol intakes with postmenopausal breast cancer among women in the Cancer Prevention Study II Nutrition Cohort. The modification of the folate associations by the other nutrients was also investigated. Design: This prospective cohort study included 70,656 postmenopausal women for whom dietary information was collected in 1992. Of these, 3898 developed breast cancer between enrollment in 1992 and June 2005. Cox proportional hazards modeling was used to calculate multivariate-adjusted hazard rate ratios and 95% CIs. Results: Compared with the lowest quintile, the highest quintile of dietary folate intake was associated with a higher risk of breast cancer (rate ratio: 1.12; 95% CI: 1.01, 1.24). However, the test for trend was not significant (P for trend = 0.15). No association was found for total folate, vitamin B-6, or vitamin B-12, but methionine was inversely associated with breast cancer risk (P for trend = 0.04). The association of dietary folate with breast cancer was not modified by other nutrients or alcohol. Conclusions: This study suggests that dietary folate intake may be positively associated with postmenopausal breast cancer. However, no dose-response relation was observed. The extent to which increased supplement use and folate fortification contributes to breast cancer risk warrants further research. © 2010 American Society for Nutrition.

Stevens V.L.,Epidemiology Research | Jacobs E.J.,Epidemiology Research | Sun J.,Epidemiology Research | McCullough M.L.,Epidemiology Research | And 4 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2012

Background: Obesity, as measured by body mass index (BMI), is an established risk factor for endometrial cancer in postmenopausal women. Weight cycling, which consists of repeated cycles of weight loss followed by regain, occurs frequently in overweight and obese women. It is unclear whether weight cycling is associated with risk of endometrial cancer independent of BMI. Methods: This analysis included 38,148 postmenopausal women enrolled in the Cancer Prevention Study II Nutrition Cohort, of whom 559 were diagnosed with endometrial cancer between enrollment in 1992 and June 30, 2007.Number of lifetime weight cycles was determined from questions on the baseline questionnaire asking how many times 10 or more pounds were intentionally lost and later regained. Multivariable-adjusted hazard rate ratios (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Results: Weight cycling was positively associated with endometrial cancer incidence (RR, 2.13; 95% CI, 1.63-2.78 for 10+weight cycles vs. no weight cycles; P trend < 0.0001). However, after adjustment for BMI in 1992, this association was null (RR, 1.05; 95% CI, 0.77-1.42; P trend = 0.82). Weight cycling was not associated with endometrial cancer in analyses stratified by BMI or by weight change after adjustment for BMI. Conclusions: After adjustment for BMI, weight cycling was not associated with the risk of endometrial cancer. Impact: These findings suggest that weight loss with subsequent regain is unlikely to increase risk of endometrial cancer. Therefore, weight loss for better health should be encouraged. ©2012 American Association for Cancer Research.

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