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01-12-2013 | Original paper

COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of colon and rectal cancers in two independent populations

Authors: Karen W. Makar, Elizabeth M. Poole, Alexa J. Resler, Brenna Seufert, Karen Curtin, Sarah E. Kleinstein, David Duggan, Richard J. Kulmacz, Li Hsu, John Whitton, Christopher S. Carlson, Christine F. Rimorin, Bette J. Caan, John A. Baron, John D. Potter, Martha L. Slattery, Cornelia M. Ulrich

Published in: Cancer Causes & Control | Issue 12/2013

Abstract

Purpose

Nonsteroidal anti-inflammatory drugs (NSAIDs) target the prostaglandin H synthase enzymes, cyclooxygenase (COX)-1 and COX-2, and reduce colorectal cancer risk. Genetic variation in the genes encoding these enzymes may be associated with changes in colon and rectal cancer risk and in NSAID efficacy.

Methods

We genotyped candidate polymorphisms and tag SNPs in PTGS1 (COX-1) and PTGS2 (COX-2) in a population-based case–control study (Diet, Activity and Lifestyle Study, DALS) of colon cancer (n = 1,470 cases/1,837 controls) and rectal cancer (n = 583/775), and independently among cases and controls from the Colon Cancer Family Registry (CCFR; colon n = 959/1,535, rectal n = 505/839).

Results

In PTGS2, a functional polymorphism (−765G>C; rs20417) was associated with a twofold increased rectal cancer risk (p = 0.05) in the DALS. This association replicated with a significant nearly fivefold increased risk of rectal cancer in the CCFR study (OR_{CC vs. GG} = 4.88; 95 % CI 1.54–15.45; OR_{GC vs. GG} = 1.36; 95 %CI 0.95–1.94). Genotype–NSAID interactions were observed in the DALS for PTGS1 and rectal cancer risk and for PTGS2 and colon cancer risk, but were no longer significant after correcting for multiple comparisons and did not replicate in the CCFR. No significant associations between PTGS1 polymorphisms and colon or rectal cancer risk were observed.

Conclusions

These findings suggest that polymorphisms in PTGS2 may be associated with rectal cancer risk and impact the protective effects of NSAIDs.

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Title: COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of colon and rectal cancers in two independent populations
Authors: Karen W. Makar
Elizabeth M. Poole
Alexa J. Resler
Brenna Seufert
Karen Curtin
Sarah E. Kleinstein
David Duggan
Richard J. Kulmacz
Li Hsu
John Whitton
Christopher S. Carlson
Christine F. Rimorin
Bette J. Caan
John A. Baron
John D. Potter
Martha L. Slattery
Cornelia M. Ulrich
Publication date: 01-12-2013
Publisher: Springer Netherlands
Published in: Cancer Causes & Control / Issue 12/2013
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-013-0282-1

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