Sunday, October 11, 2009

Aspirin blunts cancer risk

Recently I attended Harvard University's annual course on the role of the Tumor Microenvironment, Angiogenesis and Metastasis.  Dr Isaiah Fiedler, a renowned physician-scientist in the field discussed  his daily consumption of one baby aspirin per day to ward off CVD and metastasis - the real killer in cancer.  As you contemplate your daily baby aspirin consumption here is more mounting evidence.

Cyclooxygenase-2 Polymorphisms, Aspirin Treatment, and Risk for Colorectal Adenoma Recurrence—Data from a Randomized Clinical Trial

  1. Elizabeth L. Barry1,
  2. Leah B. Sansbury3,
  3. Maria V. Grau1,
  4. Iqbal U. Ali4,
  5. Shirley Tsang5,
  6. David J. Munroe5,
  7. Dennis J. Ahnen6,
  8. Robert S. Sandler7,
  9. Fred Saibil8,
  10. Jiang Gui1,
  11. Robert S. Bresalier10,
  12. Gail E. McKeown-Eyssen9,
  13. Carol Burke11 and
  14. John A. Baron1,2
+ Author Affiliations
  1. Departments of 1Community and Family Medicine and 2Medicine, Dartmouth Medical School, Lebanon, New Hampshire; Divisions of 3Cancer Control and Population Sciences and 4Cancer Prevention, National Cancer Institute, NIH, Bethesda, Maryland; 5Laboratory of Molecular Technology, Science Applications International Corporation, Inc., Frederick, Maryland; 6Department of Medicine, University of Colorado, Denver, Colorado; 7Department of Medicine, University of North Carolina, Chapel Hill, North Carolina; 8Division of Gastroenterology, Sunnybrook Health Sciences Centre; 9Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; 10Department of Gastroenterology, Hepatology and Nutrition, M.D. Anderson Cancer Center, Houston, Texas; and 11Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio
  1. Requests for reprints:
    Elizabeth L. Barry, Department of Community and Family Medicine, Dartmouth Medical School, Suite 300, Evergreen Center, 46 Centerra Parkway, Lebanon, NH 03756. Phone: 603-650-3475; Fax: 603-650-3473. E-mail: Elizabeth.L.Barry@Dartmouth.edu

Abstract

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.(Cancer Epidemiol Biomarkers Prev 2009;18(10):2726–33)