An analysis that included nearly 400,000 participants finds that those with higher blood levels of vitamin B6 and the essential amino acid methionine (found in most protein) had an associated lower risk of lung cancer, including participants who were current or former smokers, according to a study in the June 16 issue of JAMA.

Previous research has suggested that deficiencies in B vitamins may increase the probability of DNA damage and subsequent gene mutations. "Given their involvement in maintaining DNA integrity and gene expression, these nutrients have a potentially important role in inhibiting cancer development, and offer the possibility of modifying cancer risk through dietary changes," the authors write. They add that deficiencies in nutrient levels of B vitamins have been shown to be high in many western populations.

Paul Brennan, Ph.D., of the International Agency for Research on Cancer, Lyon, France, and colleagues conducted an investigation of B vitamins and methionine status based on serum samples from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study, which recruited 519,978 participants from 10 European countries between 1992 and 2000, of whom 385,747 donated blood. By 2006, 899 lung cancer cases were identified and 1,770 control participants were individually matched by country, sex, date of birth, and date of blood collection.

After an analysis of the incidence rate of lung cancer within the entire EPIC cohort and adjusting for various factors, the researchers found a lower risk for lung cancer among participants with increasing levels of B6 (comparing the fourth vs. first quartile of B6 levels). A lower risk was also seen for increasing methionine levels. "Similar and consistent decreases in risk were observed in never, former, and current smokers, indicating that results were not due to confounding by smoking. The magnitude of risk was also constant with increasing length of follow-up, indicating that the associations were not explained by preclinical disease," the researchers write.

When participants were classified by median levels of serum methionine and B6, having above-median levels of both was associated with a lower lung cancer risk overall. A moderate lower risk was observed for increasing serum folate levels, although this association was restricted to former and current smokers, and was not apparent in never smokers.

"Our results suggest that above-median serum measures of both B6 and methionine, assessed on average 5 years prior to disease onset, are associated with a reduction of at least 50 percent on the risk of developing lung cancer. An additional association for serum levels of folate was present, that when combined with B6 and methionine, was associated with a two-thirds lower risk of lung cancer," the authors write.

The researchers add that if their observations regarding serum methionine, B6, or both are shown to be causal, identifying optimum levels for reducing future cancer risk would appear to be appropriate.

"Lung cancer remains the most common cause of cancer death in the world today and is likely to remain so for the near future. It is essential that for lung cancer prevention, any additional evidence about causality does not detract from the importance of reducing the numbers of individuals who smoke tobacco. With this in mind, it is important to recognize that a large proportion of lung cancer cases occur among former smokers, making up the majority in countries where tobacco campaigns have been particularly successful, and a nontrivial number of lung cancer cases occur also among never smokers, particularly among women in parts of Asia. Clarifying the role of B vitamins and related metabolites in lung cancer risk is likely therefore to be particularly relevant for former smokers and never smokers," the authors conclude.

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