title: Processed meat intake, CYP2A6 activity and risk of colorectal adenoma.
abstract: Red and processed meat intake is associated with increased risks of both colorectal adenoma and cancer. Processed meats contain nitrate and nitrite, precursors of N-nitroso compounds (NOCs); furthermore, meats cooked at high temperatures contain heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Specific NOC, HCA and PAH are mutagens and animal carcinogens. We conducted a case-control study of 146 cases of colorectal adenoma, diagnosed at sigmoidoscopy or colonoscopy, and 228 polyp-free controls. We calculated odds ratios (ORs) [and 95% confidence intervals (CIs)] and found a 2-fold increased risk in the highest, compared with the lowest, quartile of processed meat intake (95% CI = 1.0-4.0). We estimated nitrate and nitrite intake from meat using published data from the literature as well as from actual measurements of meats analyzed recently. We evaluated the interaction of processed meat and nitrate plus nitrite intake with CYP2A6 activity, an enzyme able to metabolize some NOC to their carcinogenic form. Results for both methods of estimating nitrate and nitrite intake were similar; compared with the lowest, the highest quartile based on measured values was associated with a 2-fold elevated risk (95% CI = 1.0-3.9). Adjustment for the HCA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) attenuated the association (OR = 1.6, 95% CI = 0.8-3.2), but other HCA and PAH had minimal effect. Higher CYP2A6 activity was not associated with risk and there was no evidence of an interaction of CYP2A6 activity with nitrate and nitrite intake. Our results suggest that nitrite and nitrate intake from processed meat intake increases the risk of colorectal adenoma after accounting for HCA and PAH.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7240, USA. wardm@mail.nih.gov
authors.forename: Mary H
authors.initials: MH
authors.lastname: Ward
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.forename: Hozefa
authors.initials: H
authors.lastname: Divan
authors.forename: Martin
authors.initials: M
authors.lastname: Kulldorff
authors.forename: Susan
authors.initials: S
authors.lastname: Nowell-Kadlubar
authors.forename: Fred F
authors.initials: FF
authors.lastname: Kadlubar
authors.forename: Rashmi
authors.initials: R
authors.lastname: Sinha
mesh_terms: D000236:Adenoma / Q000201:enzymology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000502:physiology*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology*; D065637:Cytochrome P-450 CYP2A6; D004032:Diet; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008461:Meat Products; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000502:physiology*; D012307:Risk Factors
chemical_list: D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6