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CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk.
Cancer Res. 2001 May 01; 61(9):3566-9.CR

Abstract

Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has a protective effect on the incidence of colon neoplasia. However, polymorphisms in NSAID-metabolizing enzymes may alter this effect. NSAIDs, particularly aspirin, are glucuronidated by UGT1A6 and some classes of NSAIDs are also metabolized by cytochrome P450 (CYP) 2C9. Both of these enzymes have slow-metabolizing, variant forms. We tested the hypothesis that the slow alleles of these enzymes can modify the inverse association between NSAIDs and colon neoplasia in the Minnesota Cancer Prevention Research Unit (CPRU) adenomatous polyp case-control study. CYP2C9 and UGT1A6 genotypes were determined for 474 adenoma cases and 563 controls. NSAID use was inversely associated with adenoma risk [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.44-0.90 for aspirin; and OR, 0.50; 95% CI, 0.31-0.82 for nonaspirin NSAID]. However, this association was absent in aspirin users who carried the CYP2C9 variant alleles (OR, 0.88; 95% CI, 0.51-1.53) or who were homozygous wild-type UGT1A6 (OR, 0.86; 95% CI, 0.50-1.50). Carriers of both of these alleles who use aspirin were also not at reduced risk of adenomatous polyps (OR, 1.59; 95% CI, 0.68-3.73). The variants of these enzymes did not influence the association between nonaspirin NSAIDs and adenoma risk. These data indicate that the effectiveness of chemopreventive drugs can be modulated by the genotype of metabolizing enzymes.

Authors+Show Affiliations

Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. jbigler@fhcrc.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11325819

Citation

Bigler, J, et al. "CYP2C9 and UGT1A6 Genotypes Modulate the Protective Effect of Aspirin On Colon Adenoma Risk." Cancer Research, vol. 61, no. 9, 2001, pp. 3566-9.
Bigler J, Whitton J, Lampe JW, et al. CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk. Cancer Res. 2001;61(9):3566-9.
Bigler, J., Whitton, J., Lampe, J. W., Fosdick, L., Bostick, R. M., & Potter, J. D. (2001). CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk. Cancer Research, 61(9), 3566-9.
Bigler J, et al. CYP2C9 and UGT1A6 Genotypes Modulate the Protective Effect of Aspirin On Colon Adenoma Risk. Cancer Res. 2001 May 1;61(9):3566-9. PubMed PMID: 11325819.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk. AU - Bigler,J, AU - Whitton,J, AU - Lampe,J W, AU - Fosdick,L, AU - Bostick,R M, AU - Potter,J D, PY - 2001/4/28/pubmed PY - 2001/5/25/medline PY - 2001/4/28/entrez SP - 3566 EP - 9 JF - Cancer research JO - Cancer Res VL - 61 IS - 9 N2 - Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has a protective effect on the incidence of colon neoplasia. However, polymorphisms in NSAID-metabolizing enzymes may alter this effect. NSAIDs, particularly aspirin, are glucuronidated by UGT1A6 and some classes of NSAIDs are also metabolized by cytochrome P450 (CYP) 2C9. Both of these enzymes have slow-metabolizing, variant forms. We tested the hypothesis that the slow alleles of these enzymes can modify the inverse association between NSAIDs and colon neoplasia in the Minnesota Cancer Prevention Research Unit (CPRU) adenomatous polyp case-control study. CYP2C9 and UGT1A6 genotypes were determined for 474 adenoma cases and 563 controls. NSAID use was inversely associated with adenoma risk [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.44-0.90 for aspirin; and OR, 0.50; 95% CI, 0.31-0.82 for nonaspirin NSAID]. However, this association was absent in aspirin users who carried the CYP2C9 variant alleles (OR, 0.88; 95% CI, 0.51-1.53) or who were homozygous wild-type UGT1A6 (OR, 0.86; 95% CI, 0.50-1.50). Carriers of both of these alleles who use aspirin were also not at reduced risk of adenomatous polyps (OR, 1.59; 95% CI, 0.68-3.73). The variants of these enzymes did not influence the association between nonaspirin NSAIDs and adenoma risk. These data indicate that the effectiveness of chemopreventive drugs can be modulated by the genotype of metabolizing enzymes. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11325819/CYP2C9_and_UGT1A6_genotypes_modulate_the_protective_effect_of_aspirin_on_colon_adenoma_risk_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11325819 DB - PRIME DP - Unbound Medicine ER -