Vitamin B6, Methionine Linked to Lower Risk for Lung Cancer

Laurie Barclay, MD

July 07, 2010

July 7, 2010 — Serum levels of vitamin B6 and methionine were inversely associated with risk for lung cancer, according to the results of a large cohort study reported in the June 16 issue of the Journal of the American Medical Association.

"B vitamins and factors related to 1-carbon metabolism help to maintain DNA integrity and regulate gene expression and may affect cancer risk," write Mattias Johansson, PhD, and colleagues from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. "We therefore conducted a comprehensive investigation of B vitamins and methionine status based on serum samples from the [EPIC] cohort study, a large population cohort of more than 500 000 adults conducted in 10 European countries."

Between 1992 and 2000, 385,747 of the 519,978 EPIC participants donated blood samples for measurement of serum levels for 6 factors of 1-carbon metabolism and cotinine. There were 899 patients with lung cancer identified by 2006, to which 1770 control participants were matched by country, sex, birth date, and blood collection date. Primary outcomes were odds ratios (ORs) of lung cancer by serum levels of 4 B vitamins (B2, B6, folate [B9], and B12), methionine, and homocysteine.

Among never, former, and current male smokers within the entire EPIC cohort, the age-standardized incidence rates of lung cancer were 6.6, 44.9, and 156.1 per 100,000 person-years, respectively, standardized to the world population aged 35 to 79 years. For women, the corresponding incidence rates were 7.1, 23.9, and 100.9 per 100,000 person-years, respectively.

Elevated serum levels of B6 and methionine were associated with a lower risk for lung cancer after accounting for smoking. For the fourth vs first quartile of B6, the OR was 0.44 (95% confidence interval [CI], 0.33 - 0.60; P for trend < .000001). For the fourth vs first quartile of serum methionine, OR was 0.52 (95% CI, 0.39 - 0.69; P for trend < .000001). These findings did not appear to be caused by confounding by smoking because similar and consistent decreases in risk were seen in never, former, and current smokers. Nor could these associations be attributed to preclinical disease, because the magnitude of risk was constant with an increasing length of follow-up.

For former and current smokers only, risk for lung cancer was also lower with higher levels of serum folate (fourth vs first quartile OR, 0.68; 95% CI, 0.51 - 0.90; P for trend =.001). Participants with above-median levels of both serum methionine and B6 had 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 (OR, 0.42; 95% CI, 0.27 - 0.65) smokers.

"Serum levels of vitamin B6 and methionine were inversely associated with risk of lung cancer," the study authors write.

Limitations of this study include possible confounding and reliance on measurements from a single blood sample.

"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," the study authors conclude. "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."

One of the study authors is a member of the steering board of the nonprofit Foundation to Promote Research Into Functional Vitamin B12 Deficiency. The EPIC study has been supported by the Europe Against Cancer Program of the European Commission; Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia, and Navarra; the Instituto de Salud Carlos III Red de Centros de Epidemiología y Salud Pública, Spain; the Instituto de Salud Carlos III of the Spanish Ministry of Health; Cancer Research UK; Medical Research Council, United Kingdom; Greek Ministry of Health; Stavros Niarchos Foundation; Hellenic Health Foundation; Italian Association for Research on Cancer; Italian National Research Council, Fondazione-Istituto Banco Napoli, Italy; Compagnia di San Paolo; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Västerbotten, Sweden; Norwegian Cancer Society; Research Council of Norway; French League Against Cancer; National Institute for Health and Medical Research, France; Mutuelle Générale de l'Education Nationale, France; 3M Co, France; Gustave Roussy Institute, France; and General Councils of France.

JAMA. 2010;303:2377-2385. Abstract