This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Le Marchand, L. Articles by Wilkens, L. R. Search for Related Content PubMed PubMed Citation Articles by Le Marchand, L. Articles by Wilkens, L. R.

Red Meat Intake, CYP2E1 Genetic Polymorphisms, and Colorectal Cancer Risk¹

Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813

N-Nitroso compounds are suspected colorectal cancer (CRC) carcinogens to which individuals on a diet high in red meat (RM) may be particularly exposed. Many of these compounds undergo -hydroxylation by CYP2E1 to form DNA adducts. The gene coding for this enzyme is polymorphic and thus may constitute a susceptibility factor for CRC. We conducted a population-based case-control study in Hawaii to test the association of two functional polymorphisms in CYP2E1 (the G1259C RsaI substitution and a 5' 96-bp insertion variant) with CRC, as well as their modifying effects on the association of RM and processed meat (PM) with this cancer. We obtained interviews and blood samples for 521 patients with CRC (165 with rectal cancer) and 639 controls of Japanese, Caucasian, or Hawaiian origin. Genotyping was performed by PCR. After adjustment for CRC risk factors, subjects with the 5' insert variant were found to be at a 60% increased risk (95% confidence interval, 1.1–2.5) for rectal cancer. Subjects who carry the insert and who were predicted to have been exposed to increased levels of nitrosamines, based on their high intake of RM or PM, were at a markedly greater increased risk (2- and 3-fold for RM and PM, respectively) for rectal cancer. No clear association was found for colon cancer. A similar increase in rectal cancer risk was found for CYP2E1 insert carriers who consumed salted/dried fish or Oriental pickled vegetables. These data provide additional support for the hypothesis that nitrosamines are carcinogenic to the rectum in humans and that RM and, in particular, PMs are significant sources of exposure for these compounds.

This article has been cited by other articles:

				M. Luchtenborg, K. K.L. White, L. Wilkens, L. N. Kolonel, and L. Le Marchand Smoking and Colorectal Cancer: Different Effects by Type of Cigarettes? Cancer Epidemiol. Biomarkers Prev., July 1, 2007; 16(7): 1341 - 1347. [Abstract] [Full Text] [PDF]