Journal
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
Volume 303, Issue 23, Pages 2377-2385Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jama.2010.808
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Funding
- World Cancer Research Fund (United Kingdom)
- European Commission (SANCO)
- Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research
- Danish Cancer Society
- Spanish Ministry of Health, Spanish Regional Government of Andalucia
- Spanish Ministry of Health, Spanish Regional Government of Asturias
- Spanish Ministry of Health, Spanish Regional Government of Basque Country
- Spanish Ministry of Health, Spanish Regional Government of Murcia
- Spanish Ministry of Health, Spanish Regional Government of Navarra
- ISCIII Network RCESP, Spain [C03/09]
- ISCIII of the Spanish Ministry of Health [RETICC DR06/0020]
- Cancer Research UK
- Medical Research Council, United Kingdom
- Greek Ministry of Health
- Stavros Niarchos Foundation
- Hellenic Health Foundation
- Italian Association for Research on Cancer (AIRC)
- 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 Vasterbotten, Sweden
- Norwegian Cancer Society
- Research Council of Norway
- French League against Cancer (LNCC)
- National Institute for Health and Medical Research (INSERM), France
- Mutuelle Generale de l'Education Nationale (MGEN), France
- 3M Co, France
- Gustave Roussy Institute (IGR), France
- General Councils of France
- Medical Research Council [G0401527, MC_U106179471] Funding Source: researchfish
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Context B vitamins and factors related to 1-carbonmetabolism 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 (B-2, B-6, folate [B-9], and B-12), 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. JAMA. 2010; 303(23): 2377-2385
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