Tags

Type your tag names separated by a space and hit enter

Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk.

Abstract

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 alpha-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.

Links

  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

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

    , ,

    Source

    MeSH

    Case-Control Studies
    Colorectal Neoplasms
    Cytochrome P-450 CYP2E1
    Diet
    Hawaii
    Humans
    Meat
    Nitrosamines
    Odds Ratio
    Polymorphism, Genetic
    Risk Factors

    Pub Type(s)

    Journal Article
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    12376502

    Citation

    Le Marchand, Loïc, et al. "Red Meat Intake, CYP2E1 Genetic Polymorphisms, and Colorectal Cancer Risk." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 11, no. 10 Pt 1, 2002, pp. 1019-24.
    Le Marchand L, Donlon T, Seifried A, et al. Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11(10 Pt 1):1019-24.
    Le Marchand, L., Donlon, T., Seifried, A., & Wilkens, L. R. (2002). Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 11(10 Pt 1), pp. 1019-24.
    Le Marchand L, et al. Red Meat Intake, CYP2E1 Genetic Polymorphisms, and Colorectal Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2002;11(10 Pt 1):1019-24. PubMed PMID: 12376502.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk. AU - Le Marchand,Loïc, AU - Donlon,Timothy, AU - Seifried,Ann, AU - Wilkens,Lynne R, PY - 2002/10/12/pubmed PY - 2002/12/27/medline PY - 2002/10/12/entrez SP - 1019 EP - 24 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 11 IS - 10 Pt 1 N2 - 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 alpha-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. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/12376502/full_citation L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12376502 DB - PRIME DP - Unbound Medicine ER -