Study Title:

Vitamin B6 and Lung Cancer Risk

Study Abstract

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 [B9], 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 for men, 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 <.000001), as well as for serum methionine (fourth vs first quartile OR, 0.52; 95% CI, 0.39-0.69; P for trend <.000001). 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. A lower risk was also seen for serum folate (fourth vs first quartile OR, 0.68; 95% CI, 0.51-0.90; P for trend = .001), although this was apparent only for former and current smokers. 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 (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.

From press releas

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 [factors that can influence outcomes] 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 (midpoint) 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 non-trivial 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.

Study Information

Paul Brennan, et al.
Serum B Vitamin Levels and Risk of Lung Cancer
JAMA
2010 June
International Agency for Re­search on Cancer, Lyon, France

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