Serum B vitamin levels and risk of lung cancer

Mattias Johansson, Caroline Relton, Per Magne Ueland, Stein Emil Vollset, Øivind Midttun, Ottar Nygård, Nadia Slimani, Paolo Boffetta, Mazda Jenab, Françoise Clavel-Chapelon, Marie Christine Boutron-Ruault, Guy Fagherazzi, Rudolf Kaaks, Sabine Rohrmann, Heiner Boeing, Cornelia Weikert, H. Bas Buenode-Mesquita, Martine M. Ros, Carla H. Van Gils, Petra H.M. PeetersAntonio Agudo, Aurelio Barricarte, Carmen Navarro, Laudina Rodríguez, Maria José Sánchez, Nerea Larrañaga, Kay Tee Khaw, Nick Wareham, Naomi E. Allen, Francesca Crowe, Valentina Gallo, Teresa Norat, Vittorio Krogh, Giovanna Masala, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Torgny Rasmuson, Göran Hallmans, Elio Riboli, Paolo Vineis, Paul Brennan*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    142 Citations (Scopus)


    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 <.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.

    Original languageEnglish
    Pages (from-to)2377-2385
    Number of pages9
    JournalJAMA - Journal of the American Medical Association
    Issue number23
    Publication statusPublished - 16 Jun 2010


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