Carcinogenesis Advance Access originally published online on February 2, 2007
Carcinogenesis 2007 28(6):1210-1216; doi:10.1093/carcin/bgm009
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Published by Oxford University Press 2007.
Processed meat intake, CYP2A6 activity and risk of colorectal adenoma
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7240, USA
1 Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA 90095
2 Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, MA, 02215
3 Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
4 Department of Epidemiology, College of Public Health, and Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205
* To whom correspondence should be addressed. Tel: +1 301 435 4713; Fax: +1 301 402 1819; Email: wardm{at}mail.nih.gov
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.
Abbreviations: BaP, benzo[a]pyrene; CI, confidence interval; HCA, heterocyclic amine; IQR, interquartile range; MeIQx, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline; NOC, N-nitroso compound; OR, odds ratio; PAH, polycyclic aromatic hydrocarbon
Received September 19, 2006; revised December 23, 2006; accepted January 4, 2007.