Format

Send to:

Choose Destination
See comment in PubMed Commons below
JAMA Intern Med. 2014 May;174(5):732-9. doi: 10.1001/jamainternmed.2014.511.

Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of colon cancer.

Author information

  • 1Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
  • 2Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands2Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
  • 3Medical Research Council Clinical Trials Unit, University College, London, England.
  • 4Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
  • 5Comprehensive Cancer Centre South, Eindhoven Cancer Registry, Eindhoven, the Netherlands.
  • 6PHARMO Institute for Drug Outcomes Research, Utrecht, the Netherlands.
  • 7Department of Experimental Pathology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Abstract

IMPORTANCE:

Use of aspirin (which inhibits platelet function) after a colon cancer diagnosis is associated with improved overall survival. Identifying predictive biomarkers of this effect could individualize therapy and decrease toxic effects.

OBJECTIVE:

To demonstrate that survival benefit associated with low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA class I antigen expression.

DESIGN, SETTING, AND PARTICIPANTS:

A cohort study with tumor blocks from 999 patients with colon cancer (surgically resected between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were obtained from a prescription database. Parametric survival models with exponential (Poisson) distribution were used to model the survival.

MAIN OUTCOMES AND MEASURES:

Overall survival.

RESULTS:

The overall survival benefit associated with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio (RR) of 0.53 (95% CI, 0.38-0.74; P < .001) when tumors expressed HLA class I antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen expression was lost. The benefit of aspirin was similar for tumors with strong PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38-0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P < .001). No association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44).

CONCLUSIONS AND RELEVANCE:

Contrary to the original hypothesis, aspirin use after colon cancer diagnosis was associated with improved survival if tumors expressed HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin. HLA class I antigen might serve as a predictive biomarker for adjuvant aspirin therapy in colon cancer.

PMID:
24687028
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems
    Loading ...
    Write to the Help Desk