title: Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study.
abstract: BACKGROUND
  Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but human evidence of their role is scarce for esophageal cancer and inconsistent for gastric cancer.
  
  
  OBJECTIVE
  We studied the relation between risks of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite, and nitrate in the Netherlands Cohort Study.
  
  
  METHODS
  A total of 120,852 men and women aged 55-69 y were recruited in 1986, and diet, based on a 150-item food-frequency questionnaire, and other risk factors were assessed. The cohort was followed for 16.3 y, and 110 esophageal squamous cell carcinoma (ESCC), 151 esophageal adenocarcinoma, 166 gastric cardia adenocarcinoma, and 497 gastric noncardia adenocarcinoma (GNCA) cases were analyzed along with 4032 subcohort members in a case-cohort analysis.
  
  
  RESULTS
  Positive associations were observed between N-nitrosodimethylamine intake and ESCC risk (HR for 0.1-μg/d increase in intake: 1.15; 95% CI: 1.05, 1.25; P-trend = 0.01 based on tertiles of intake) and GNCA risk (1.06; 95% CI: 1.01, 1.10; P-trend = 0.09) in men. ESCC risk was associated with nitrite intake (HR for 0.1-mg/d increase: 1.19; 95% CI: 1.05, 1.36; P-trend = 0.06) and heme-iron intake (HR for 1-mg/d increase: 1.83; 95% CI: 0.98, 3.39; P-trend = 0.03). Among women, exposure levels were lower, and we found no convincing positive associations.
  
  
  CONCLUSIONS
  These results suggest that N-nitroso compounds may influence the risk of ESCC in men, but there are no clear associations for other esophageal and gastric subtypes.
authors.affiliation: School for Oncology and Developmental Biology, Department of Epidemiology, Maastricht University, Maastricht, Netherlands. andras.keszei@maastrichtuniversity.nl
authors.forename: András P
authors.initials: AP
authors.lastname: Keszei
authors.forename: R Alexandra
authors.initials: RA
authors.lastname: Goldbohm
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Schouten
authors.forename: Paula
authors.initials: P
authors.lastname: Jakszyn
authors.forename: Piet A
authors.initials: PA
authors.lastname: van den Brandt
mesh_terms: D000368:Aged; D001205:Ascorbic Acid / Q000008:administration & dosage; D002734:Chlorophyll / Q000008:administration & dosage; D004032:Diet; D004128:Dimethylnitrosamine / Q000009:adverse effects*; D004938:Esophageal Neoplasms / Q000209:etiology / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019266:Iron, Dietary / Q000009:adverse effects; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009426:Netherlands; D009566:Nitrates / Q000009:adverse effects; D009573:Nitrites / Q000009:adverse effects; D015538:Nitrosation; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000209:etiology / Q000473:pathology*; D011795:Surveys and Questionnaires
chemical_list: D019266:Iron, Dietary; D009566:Nitrates; D009573:Nitrites; D002734:Chlorophyll; D004128:Dimethylnitrosamine; D001205:Ascorbic Acid