title: Alcohol and Dietary Folate Intake and Promoter CpG Island Methylation in Clear-Cell Renal Cell Cancer.
abstract: We investigated whether alcohol and dietary folate intakes were associated with promoter methylation in clear-cell renal cell carcinoma (ccRCC). The Netherlands Cohort Study with a case-cohort design included 120,852 subjects aged 55-69 yr in 1986. Diet was measured with a food-frequency questionnaire. After 20.3 yr of follow-up, paraffin-embedded tumor blocks were collected. Methylation-specific polymerase chain reaction (MSP) was used to analyze promoter methylation of 11 genes. ccRCC cases were classified into low (0-19% of the genes), intermediate (20-39%), and high (40%+) methylation. Multivariable Cox regression analyses were conducted, stratified according to methylation, including 3980 subcohort members and 297 ccRCC cases. Increasing alcohol intake was associated with decreased ccRCC risk, but was not statistically significant; multivariable adjusted hazard ratio (HR) for ≥30 g alcohol/day versus 0 g/day was 0.78 [95% confidence interval (CI): 0.48-1.24], and P-value for trend was 0.46. In strata according to methylation index, no significant heterogeneity was observed. Dietary folate intake was not associated with ccRCC risk. There was no significant heterogeneity between strata according to methylation index. There was no effect modification of alcohol and dietary folate intake on ccRCC risk, nor in strata according to methylation index. Our findings do not support the hypothesis that alcohol and dietary folate intakes are involved in ccRCC.
authors.affiliation: a Department of Epidemiology , School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Schouten
authors.affiliation: a Department of Epidemiology , School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Ivette A G
authors.initials: IA
authors.lastname: Deckers
authors.affiliation: a Department of Epidemiology , School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre , Maastricht , The Netherlands.|b Department of Epidemiology , School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
authors.affiliation: c Department of Pathology , Antwerp University Hospital , Edegem , Belgium.
authors.forename: Marcella M L L
authors.initials: MM
authors.lastname: Baldewijns
authors.affiliation: d Department of Pathology , School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre , Maastricht , The Netherlands.
authors.forename: Manon
authors.initials: M
authors.lastname: van Engeland
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D015331:Cohort Studies; D018899:CpG Islands; D019175:DNA Methylation; D000072001:Diet, Healthy; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D005494:Folic Acid Deficiency / Q000503:physiopathology; D005500:Follow-Up Studies; D006801:Humans; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010349:Patient Compliance; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012042:Registries; D015203:Reproducibility of Results; D012306:Risk; D057566:Self Report
chemical_list: D005492:Folic Acid