Pancreatic cancer risk and nutrition-related methyl-group availability indicators in male smokers

Background: Few risk factors for pancreatic cancer have been identified, wi th age and cigarette smoking being the most consistent. The protective effe ct associated with consumption of fruits and vegetables-the major dietary s ources of folate-is suggestive of a role for factors influencing cellular m ethylation reactions; however, to our knowledge, no study has investigated this relationship. Whether biochemical indicators of methyl-group availabil ity are associated with exocrine pancreatic cancer risk was the focus of th is investigation. Methods: We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29133 male Finnish smokers aged 50-69 years. One hundred twenty-six subjects wit h incident exocrine pancreatic cancer were matched by date of baseline bloo d draw (+/-30 days), study center, age (+/-5 years), trial intervention gro up, and completion of dietary history to 247 control subjects, who were ali ve and free from cancer at the time the case subjects were diagnosed. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined by use of c onditional logistic regression. Reported P values are two-tailed. Results: Serum folate and pyridoxal-5'-phosphate (PLP) concentrations showed statist ically significant inverse dose-response relationships with pancreatic canc er risk, with the highest serum tertiles having approximately half the risk of the lowest (folate: OR = 0.45; 95% CI = 0.24-0.82; P for trend =.009, a nd PLP: OR = 0.48; 95% CI = 0.26-0.88; P for trend =.02), An increased panc reatic cancer risk was also observed with greater exposure to cigarettes (e .g., pack-years [number of packs smoked per day x number of years of smokin g], highest versus lowest quartile: OR = 2.13; 95% CP = 1.13-3.99; P for tr end =.04). Conclusions: These results support the hypothesis that maintaini ng adequate folate and pyridoxine status may reduce the risk of pancreatic cancer and confirm the risk previously associated with cigarette smoking.