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Polymorphisms in PTGS1 (=COX-1) and risk of colorectal polyps.

Abstract

Two isoforms of prostaglandin H synthase (PTGS = COX) are key enzymes in prostaglandin synthesis and primary targets for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). Use of aspirin or other NSAIDs is associated with a lower risk and reduced recurrence of colorectal adenomas, established precursors of adenocarcinoma. This study investigated risk of colorectal adenomatous and hyperplastic polyps associated with several polymorphisms in the coding region of PTGS1. Within the Minnesota polyp case-control study, patients with colorectal adenomatous (n = 521) or hyperplastic (n = 194) polyps and n = 621 polyp-free controls were genotyped for four PTGS1 polymorphisms (R8W, L15-L16del, P17L, L237M); these had been predicted to affect protein function based on sequence-homology software. Age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed. Whereas there was no appreciable difference in adenoma or hyperplastic polyp risk associated with R8W, P17L, and L237M, an increased risk was observed for individuals heterozygous for the L15-L16del polymorphism (OR = 3.6, 95% CI 1.2-11.2). The variant L15-L16del allele appeared to be associated with a stronger increase in adenoma risk among nonusers of aspirin/other NSAIDs. The reduced risk observed with aspirin/other NSAID use was limited to those wild type for P17L [PP users: OR = 0.6 (0.5-0.8) versus PP nonusers: 1.0 (referent) (P interaction = 0.03)]. To our knowledge, this study represents the first investigation of polymorphisms in PTGS1 and risk of colorectal polyps. The L15-L16del variant allele may result in an increased risk of colorectal adenomas, whereas P17L may be relevant to the pharmacogenetics of aspirin. These preliminary findings require confirmation in larger studies of colorectal neoplasia.

Authors+Show Affiliations

Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M4-B402, Seattle, WA 98109-1024, USA. nulrich@fhcrc.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15159324

Citation

Ulrich, Cornelia M., et al. "Polymorphisms in PTGS1 (=COX-1) and Risk of Colorectal Polyps." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 13, no. 5, 2004, pp. 889-93.
Ulrich CM, Bigler J, Sparks R, et al. Polymorphisms in PTGS1 (=COX-1) and risk of colorectal polyps. Cancer Epidemiol Biomarkers Prev. 2004;13(5):889-93.
Ulrich, C. M., Bigler, J., Sparks, R., Whitton, J., Sibert, J. G., Goode, E. L., ... Potter, J. D. (2004). Polymorphisms in PTGS1 (=COX-1) and risk of colorectal polyps. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 13(5), pp. 889-93.
Ulrich CM, et al. Polymorphisms in PTGS1 (=COX-1) and Risk of Colorectal Polyps. Cancer Epidemiol Biomarkers Prev. 2004;13(5):889-93. PubMed PMID: 15159324.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polymorphisms in PTGS1 (=COX-1) and risk of colorectal polyps. AU - Ulrich,Cornelia M, AU - Bigler,Jeannette, AU - Sparks,Rachel, AU - Whitton,John, AU - Sibert,Justin G, AU - Goode,Ellen L, AU - Yasui,Yutaka, AU - Potter,John D, PY - 2004/5/26/pubmed PY - 2004/9/8/medline PY - 2004/5/26/entrez SP - 889 EP - 93 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 - 13 IS - 5 N2 - Two isoforms of prostaglandin H synthase (PTGS = COX) are key enzymes in prostaglandin synthesis and primary targets for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). Use of aspirin or other NSAIDs is associated with a lower risk and reduced recurrence of colorectal adenomas, established precursors of adenocarcinoma. This study investigated risk of colorectal adenomatous and hyperplastic polyps associated with several polymorphisms in the coding region of PTGS1. Within the Minnesota polyp case-control study, patients with colorectal adenomatous (n = 521) or hyperplastic (n = 194) polyps and n = 621 polyp-free controls were genotyped for four PTGS1 polymorphisms (R8W, L15-L16del, P17L, L237M); these had been predicted to affect protein function based on sequence-homology software. Age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed. Whereas there was no appreciable difference in adenoma or hyperplastic polyp risk associated with R8W, P17L, and L237M, an increased risk was observed for individuals heterozygous for the L15-L16del polymorphism (OR = 3.6, 95% CI 1.2-11.2). The variant L15-L16del allele appeared to be associated with a stronger increase in adenoma risk among nonusers of aspirin/other NSAIDs. The reduced risk observed with aspirin/other NSAID use was limited to those wild type for P17L [PP users: OR = 0.6 (0.5-0.8) versus PP nonusers: 1.0 (referent) (P interaction = 0.03)]. To our knowledge, this study represents the first investigation of polymorphisms in PTGS1 and risk of colorectal polyps. The L15-L16del variant allele may result in an increased risk of colorectal adenomas, whereas P17L may be relevant to the pharmacogenetics of aspirin. These preliminary findings require confirmation in larger studies of colorectal neoplasia. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/15159324/Polymorphisms_in_PTGS1__=COX_1__and_risk_of_colorectal_polyps_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15159324 DB - PRIME DP - Unbound Medicine ER -