Abstract

Abstract Background: B-vitamins including folate help to ensure DNA integrity and the regulation of gene expression and may be associated with subsequent reduced cancer risk. One previous cohort study among smokers identified a substantial protective effect for vitamin B6 on lung cancer. Methods: The EPIC study population included 385,747 participants from 23 centres in ten countries who completed a dietary questionnaire and provided a blood sample at recruitment between 1992 and 2000. 899 lung cancer cases were identified by 2006, with an average follow-up of 5 years, and matched to 1,770 controls for country, sex, date of birth and time of blood collection. Circulating concentrations were measured for four specific B-vitamins (B2, B6, folate and B12) as well as methionine, homocysteine and cotinine. Results: After adjusting for matching variables and cotinine, a substantial decreasing risk for lung cancer was seen for increasing levels of B6 (relative risk of 4th vs 1st quartile [RR] = 0·44, with 95% confidence interval [CI] 0·33-0·60; p for trend [ptrend]<0·000001), as well as for methionine (RR=0·52, CI 0·39-0·69; ptrend<0·000001). Similar and consistent decreases in risk were observed for never, former and current smokers, indicating that results were not due to a smoking associated artifact. The magnitude of risk was also constant with increasing length of follow-up, indicating the effects were not explained by pre-clinical disease. A decrease in risk was also seen for folate, (RR=0·68, CI 0·51-0·90; ptrend=0·001), although this was apparent only for former and current smokers. When participants were classified by median levels of both methionine and B6, having above median levels of both resulted in a substantial decrease in lung cancer risk overall (RR=0·41, CI 0·31-0·54), as well as separately among never (RR=0·36, CI 0·18-0·71), former (RR=0·51, CI 0·34-0·76), and current smokers (RR=0·42 CI 0·27-0·65). Interpretation: Higher serum levels of both vitamin B6 and methionine were associated with a substantial decrease in lung cancer risk on average 5 years later, indicating that they, or strongly related dietary factors, have an important effect on future lung cancer development. Increased knowledge of protective factors for lung cancer over and above tobacco cessation could make a significant contribution to disease prevention, particularly in former and never smokers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5727.

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