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Cancer Causes & Control
Published in: Cancer Causes & Control 8/2013

Open Access 01-08-2013 | Original paper

Common variants in genes coding for chemotherapy metabolizing enzymes, transporters, and targets: a case–control study of contralateral breast cancer risk in the WECARE Study

Authors: Jennifer D. Brooks, Sharon N. Teraoka, Leslie Bernstein, Lene Mellemkjær, Kathleen E. Malone, Charles F. Lynch, Robert W. Haile, Patrick Concannon, Anne S. Reiner, David J. Duggan, Katherine Schiermeyer, Jonine L. Bernstein, Jane C. Figueiredo, The WECARE Study Collaborative Group

Published in: Cancer Causes & Control | Issue 8/2013

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Abstract

Purpose

Women who receive chemotherapy for a first primary breast cancer have been observed to have a reduced risk of contralateral breast cancer (CBC), however, whether the genetic profile of a patient modifies this protective effect is currently not understood. The purpose of this study is to investigate the impact of germline genetic variation in genes coding for drug metabolizing enzymes, transporters, and targets on the association between chemotherapy and risk of CBC.

Methods

From the population-based Women’s Environment Cancer and Radiation Epidemiology (WECARE) Study, we included 636 Caucasian women with CBC (cases) and 1,224 women with unilateral breast cancer (controls). The association between common chemotherapeutic regimens, CMF and FAC/FEC, and risk of CBC stratified by genotype of 180 single nucleotide polymorphisms in 14 genes selected for their known involvement in metabolism, action, and transport of breast cancer chemotherapeutic agents, were determined using conditional logistic regression.

Results

CMF (RR = 0.5, 95 % CI 0.4, 0.7) and FAC/FEC (RR = 0.7, 95 % CI 0.4, 1.0) are associated with lower CBC risk relative to no chemotherapy in multivariable-adjusted models. Here we show that genotype of selected genes involved in the metabolism and uptake of these therapeutic agents does not significantly alter the protective effect of either CMF or FAC/FEC on risk of CBC.

Conclusion

The results of this study show that germline genetic variation in selected gene does not significantly alter the protective effect of CMF, FAC, and FEC on risk of CBC.
Appendix
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Metadata
Title
Common variants in genes coding for chemotherapy metabolizing enzymes, transporters, and targets: a case–control study of contralateral breast cancer risk in the WECARE Study
Authors
Jennifer D. Brooks
Sharon N. Teraoka
Leslie Bernstein
Lene Mellemkjær
Kathleen E. Malone
Charles F. Lynch
Robert W. Haile
Patrick Concannon
Anne S. Reiner
David J. Duggan
Katherine Schiermeyer
Jonine L. Bernstein
Jane C. Figueiredo
The WECARE Study Collaborative Group
Publication date
01-08-2013
Publisher
Springer Netherlands
Published in
Cancer Causes & Control / Issue 8/2013
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-013-0237-6

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