title: N-Nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study.
abstract: BACKGROUND
  Humans are exposed to preformed N-nitroso compounds (NOCs) and endogenous NOCs. Several NOCs are potential human carcinogens, including N-nitrosodimethylamine (NDMA), but evidence from population studies is inconsistent.
  
  
  OBJECTIVE
  We examined the relation between dietary NOCs (NDMA), the endogenous NOC index, and dietary nitrite and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, United Kingdom, study.
  
  
  METHODS
  This was a prospective study of 23,363 men and women, aged 40-79 y, who were recruited in 1993-1997 and followed up to 2008. The baseline diet was assessed with food-frequency questionnaires.
  
  
  RESULTS
  There were 3268 incident cancers after a mean follow-up of 11.4 y. Dietary NDMA intake was significantly associated with increased cancer risk in men and women [hazard ratio (HR): 1.14; 95% CI: 1.03, 1.27; P for trend = 0.03] and in men (HR: 1.24; 95% CI: 1.07, 1.44; P for trend = 0.005) when the highest quartile was compared with the lowest quartile in age- and sex-adjusted analyses but not in multivariate analyses (HR: 1.10; 95% CI: 0.97, 1.24; HR for men: 1.18; 95% CI: 1.00, 1.40; P for trend ≥ 0.05). When continuously analyzed, NDMA was associated with increased risk of gastrointestinal cancers (HR: 1.13; 95% CI: 1.00, 1.28), specifically of rectal cancer (HR: 1.46; 95% CI: 1.16, 1.84) per 1-SD increase after adjustment for age, sex, body mass index, cigarette smoking status, alcohol intake, energy intake, physical activity, education, and menopausal status (in women). The endogenous NOC index and dietary nitrite were not significantly associated with cancer risk. There was a significant interaction between plasma vitamin C concentrations and dietary NDMA intake on cancer incidence (P for interaction < 0.00001).
  
  
  CONCLUSIONS
  Dietary NOC (NDMA) was associated with a higher gastrointestinal cancer incidence, specifically of rectal cancer. Plasma vitamin C may modify the relation between NDMA exposure and cancer risk.
authors.affiliation: Medical Research Council Centre for Nutritional Epidemiology in Cancer Prevention and Survival, University of Cambridge, Cambridge, United Kingdom. yet@srl.cam.ac.uk
authors.forename: Yet Hua
authors.initials: YH
authors.lastname: Loh
authors.forename: Paula
authors.initials: P
authors.lastname: Jakszyn
authors.forename: Robert N
authors.initials: RN
authors.lastname: Luben
authors.forename: Angela A
authors.initials: AA
authors.lastname: Mulligan
authors.forename: Panagiota N
authors.initials: PN
authors.lastname: Mitrou
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
mesh_terms: D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000097:blood; D002273:Carcinogens / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity*; D004032:Diet / Q000009:adverse effects; D004128:Dimethylnitrosamine / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D005060:Europe; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D019266:Iron, Dietary / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008460:Meat / Q000009:adverse effects; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology*; D009573:Nitrites / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D009603:Nitroso Compounds / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity*; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology; D012306:Risk; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D002273:Carcinogens; D019266:Iron, Dietary; D009573:Nitrites; D009603:Nitroso Compounds; D004128:Dimethylnitrosamine; D001205:Ascorbic Acid