title: Serum B vitamin levels and risk of lung cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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 B(6) (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 B(6), 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).
  
  
  CONCLUSIONS
  Serum levels of vitamin B(6) and methionine were inversely associated with risk of lung cancer.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Mattias
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authors.lastname: Johansson
authors.forename: Caroline
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authors.lastname: Relton
authors.forename: Per Magne
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authors.forename: Øivind
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authors.forename: Martine M
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authors.lastname: Ros
authors.forename: Carla H
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authors.lastname: van Gils
authors.forename: Petra H M
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authors.lastname: Peeters
authors.forename: Antonio
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authors.lastname: Agudo
authors.forename: Aurelio
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authors.lastname: Barricarte
authors.forename: Carmen
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authors.lastname: Navarro
authors.forename: Laudina
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authors.lastname: Rodríguez
authors.forename: Maria-José
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authors.lastname: Sánchez
authors.forename: Nerea
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authors.lastname: Larrañaga
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nick
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authors.lastname: Wareham
authors.forename: Naomi E
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authors.lastname: Allen
authors.forename: Francesca
authors.initials: F
authors.lastname: Crowe
authors.forename: Valentina
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authors.lastname: Gallo
authors.forename: Teresa
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authors.lastname: Norat
authors.forename: Vittorio
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authors.lastname: Krogh
authors.forename: Giovanna
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authors.lastname: Masala
authors.forename: Salvatore
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authors.lastname: Panico
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Pagona
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authors.lastname: Lagiou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Torgny
authors.initials: T
authors.lastname: Rasmuson
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Elio
authors.initials: E
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authors.forename: Paolo
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mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000097:blood* / Q000453:epidemiology* / Q000517:prevention & control; D008297:Male; D008715:Methionine / Q000097:blood*; D008875:Middle Aged; D016017:Odds Ratio; D012306:Risk; D025101:Vitamin B 6 / Q000097:blood*; D014803:Vitamin B Complex / Q000097:blood
chemical_list: D014803:Vitamin B Complex; D025101:Vitamin B 6; D008715:Methionine