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Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps.

Abstract

Prostacyclin synthase (PGIS) and arachidonate 5-lipoxygenase (ALOX5) are enzymes relevant to prostaglandin and leukotriene synthesis, both important pathways for colon cancer risk. We hypothesized that genetic variation altering the function of these enzymes would modify risk of colorectal polyps. In a Minnesota-based case-control study of adenomatous (n = 517) or hyperplastic (n = 192) polyps versus polyp-free controls (n = 618), we investigated the role of promoter repeat polymorphisms in PGIS and ALOX5 as well as ALOX5 -1700 G>A. Having fewer than six repeats on both PGIS alleles (<6R/<6R) was associated with an increased risk of adenomas compared with the 6R/6R (wild-type) genotype (OR, 1.90; 95% CI, 1.09-3.30). Having more repeats (>6R/> or =6R) reduced risk (OR, 0.73; 95% CI, 0.40-1.35; P(trend) = 0.03). In allele-based analyses, fewer repeats were associated with a modestly increased risk of adenomas and perhaps hyperplastic polyps. There were no risk differences for either the ALOX5 VNTR or -1700 G>A polymorphisms. Associations with regular use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) differed by PGIS genotype. Among individuals with at least one wild-type allele, NSAID use was associated with a decreased risk; however, those with fewer PGIS repeats (<6R/<6R) did not benefit (P(interaction) = 0.06). There was also evidence of an interaction between the COX-2 -765 G>C and ALOX5 -1700 G>A genotypes (P(interaction) = 0.07). The PGIS promoter polymorphism may affect risk of colorectal polyps and modify the effects of NSAID use on polyp risk. A more comprehensive investigation of genetic variability in prostaglandin synthesis in relation to risk of colorectal neoplasia and NSAID pharmacogenetics is warranted.

Authors+Show Affiliations

Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109-1024, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16537708

Citation

Poole, Elizabeth M., et al. "Prostacyclin Synthase and Arachidonate 5-lipoxygenase Polymorphisms 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. 15, no. 3, 2006, pp. 502-8.
Poole EM, Bigler J, Whitton J, et al. Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps. Cancer Epidemiol Biomarkers Prev. 2006;15(3):502-8.
Poole, E. M., Bigler, J., Whitton, J., Sibert, J. G., Potter, J. D., & Ulrich, C. M. (2006). Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms 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, 15(3), pp. 502-8.
Poole EM, et al. Prostacyclin Synthase and Arachidonate 5-lipoxygenase Polymorphisms and Risk of Colorectal Polyps. Cancer Epidemiol Biomarkers Prev. 2006;15(3):502-8. PubMed PMID: 16537708.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps. AU - Poole,Elizabeth M, AU - Bigler,Jeannette, AU - Whitton,John, AU - Sibert,Justin G, AU - Potter,John D, AU - Ulrich,Cornelia M, PY - 2006/3/16/pubmed PY - 2006/7/20/medline PY - 2006/3/16/entrez SP - 502 EP - 8 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 - 15 IS - 3 N2 - Prostacyclin synthase (PGIS) and arachidonate 5-lipoxygenase (ALOX5) are enzymes relevant to prostaglandin and leukotriene synthesis, both important pathways for colon cancer risk. We hypothesized that genetic variation altering the function of these enzymes would modify risk of colorectal polyps. In a Minnesota-based case-control study of adenomatous (n = 517) or hyperplastic (n = 192) polyps versus polyp-free controls (n = 618), we investigated the role of promoter repeat polymorphisms in PGIS and ALOX5 as well as ALOX5 -1700 G>A. Having fewer than six repeats on both PGIS alleles (<6R/<6R) was associated with an increased risk of adenomas compared with the 6R/6R (wild-type) genotype (OR, 1.90; 95% CI, 1.09-3.30). Having more repeats (>6R/> or =6R) reduced risk (OR, 0.73; 95% CI, 0.40-1.35; P(trend) = 0.03). In allele-based analyses, fewer repeats were associated with a modestly increased risk of adenomas and perhaps hyperplastic polyps. There were no risk differences for either the ALOX5 VNTR or -1700 G>A polymorphisms. Associations with regular use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) differed by PGIS genotype. Among individuals with at least one wild-type allele, NSAID use was associated with a decreased risk; however, those with fewer PGIS repeats (<6R/<6R) did not benefit (P(interaction) = 0.06). There was also evidence of an interaction between the COX-2 -765 G>C and ALOX5 -1700 G>A genotypes (P(interaction) = 0.07). The PGIS promoter polymorphism may affect risk of colorectal polyps and modify the effects of NSAID use on polyp risk. A more comprehensive investigation of genetic variability in prostaglandin synthesis in relation to risk of colorectal neoplasia and NSAID pharmacogenetics is warranted. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/16537708/Prostacyclin_synthase_and_arachidonate_5_lipoxygenase_polymorphisms_and_risk_of_colorectal_polyps_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=16537708 DB - PRIME DP - Unbound Medicine ER -