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 Journal Article

   

Authors:	Brooks, J. D.; Teraoka, S. N.; Bernstein, L.; Mellemkjær, L.; Malone, K. E.; Lynch, C. F.; Haile, R. W.; Concannon, P.; Reiner, A. S.; Duggan, D. J.; Schiermeyer, K.; Bernstein, J. L.; Figueiredo, J. C.
Article 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
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. © 2013 The Author(s).
Keywords:	chemotherapy; genetic variation; contralateral breast cancer; cmf
Journal Title:	Cancer Causes & Control
Volume:	24
Issue:	8
ISSN:	0957-5243
Publisher:	Springer
Date Published:	2013-08-01
Start Page:	1605
End Page:	1614
Language:	English
DOI:	10.1007/s10552-013-0237-6
PROVIDER:	scopus
PMCID:	PMC3709075
PUBMED:	23775025
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84880325786&partnerID=40&md5=e0dbf58d3cca586bc1b0444e9c9c6c37
Notes:	--- - "Export Date: 1 August 2013" - "CODEN: CCCNE" - "Source: Scopus"

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