Context: B vitamins and factors related to 1-carbon metabolism help to maintain DNA integrity and regulate gene expression and may affect cancer risk. Objective: To investigate if 1-carbon metabolism factors are associated with onset of lung cancer. Design, Setting, and Participants: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 519 978 participants from 10 countries between 1992 and 2000, of whom 385 747 donated blood. By 2006, 899 lung cancer cases were identified and 1770 control participants were individually matched by country, sex, date of birth, and date of blood collection. Serum levels were measured for 6 factors of 1-carbon metabolism and cotinine. Main Outcome Measure: Odds ratios (ORs) of lung cancer by serum levels of 4 B vitamins (B2, B6, folate [B 9], and B12), methionine, and homocysteine. Results: Within the entire EPIC cohort, the age-standardized incidence rates of lung cancer (standardized to the world population, aged 35-79 years) were 6.6, 44.9, and 156.1 per 100 000 person-years among never, former, and current smokers formen, respectively. The corresponding incidence rates for women were 7.1, 23.9, and 100.9 per 100 000 person-years, respectively. After accounting for smoking, a lower risk for lung cancer was seen for elevated serum levels of B6 (fourth vs first quartile OR, 0.44; 95% confidence interval [CI], 0.33-0.60; P for trend 6, having above-median levels of both was associated with a lower lung cancer risk overall (OR, 0.41; 95% CI, 0.31-0.54), as well as separately among never (OR, 0.36; 95% CI, 0.18-0.72), former (OR, 0.51; 95% CI, 0.34-0.76), and current smokers (OR,0.42; 95% CI, 0.27-0.65). Conclusion: Serum levels of vitamin B6 and methionine were inversely associated with risk of lung cancer.
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