| Autor: |
Barry EL; Department of Community and Family Medicine, Dartmouth Medical School, Suite 300, Evergreen Center, 46 Centerra Parkway, Lebanon, NH 03756, USA. Elizabeth.L.Barry@Dartmouth.edu, Sansbury LB, Grau MV, Ali IU, Tsang S, Munroe DJ, Ahnen DJ, Sandler RS, Saibil F, Gui J, Bresalier RS, McKeown-Eyssen GE, Burke C, Baron JA |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2009 Oct; Vol. 18 (10), pp. 2726-33. Date of Electronic Publication: 2009 Sep 15. |
| DOI: |
10.1158/1055-9965.EPI-09-0363 |
| Abstrakt: |
Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the production of prostaglandins, potent mediators of inflammation. Chronic inflammation plays an important role in the development and progression of colorectal cancer. Aspirin inhibits COX-2 activity and lowers the risk for colorectal adenomas and cancer. We investigated whether common genetic variation in COX-2 influenced risk for colorectal adenoma recurrence among 979 participants in the Aspirin/Folate Polyp Prevention Study who were randomly assigned to placebo or aspirin and followed for 3 years for the occurrence of new adenomas. Of these participants, 44.2% developed at least one new adenoma during follow-up. Adjusted relative risks and 95% confidence intervals (95% CI) were calculated to test the association between genetic variation at six COX-2 single-nucleotide polymorphisms and adenoma occurrence and interaction with aspirin treatment. Two single-nucleotide polymorphisms were significantly associated with increased adenoma recurrence: for rs5277, homozygous carriers of the minor C allele had a 51% increased risk compared with GG homozygotes (relative risk, 1.51; 95% CI, 1.01-2.25), and for rs4648310, heterozygous carriers of the minor G allele had a 37% increased risk compared with AA homozygotes (relative risk, 1.37; 95% CI, 1.05-1.79). (There were no minor allele homozygotes.) In stratified analyses, there was suggestive evidence that rs4648319 modified the effect of aspirin. These results support the hypothesis that COX-2 plays a role in the etiology of colon cancer and may be a target for aspirin chemoprevention and warrant further investigation in other colorectal adenoma and cancer populations. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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