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

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; WECARE Study Collaborative Group

doi:10.1007/s10552-013-0237-6

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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

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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

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, …

Cancer causes & control, Vol.24(8), pp.1605-1614

08/2013

DOI: 10.1007/s10552-013-0237-6

PMCID: PMC3709075

PMID: 23775025

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Abstract

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. 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. 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. 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.

United States - epidemiology

Prognosis

Follow-Up Studies

Humans

Middle Aged

Breast Neoplasms - etiology

Methyltransferases - genetics

Germ-Line Mutation - genetics

Case-Control Studies

Young Adult

Membrane Transport Proteins - genetics

Polymerase Chain Reaction

Adult

Female

Registries

Antineoplastic Agents - pharmacology

Breast Neoplasms - epidemiology

Genetic Predisposition to Disease

Genome-Wide Association Study

Pharmacogenetics

Risk Factors

Genotype

Breast Neoplasms - drug therapy

Cytochrome P-450 Enzyme System - genetics

Polymorphism, Single Nucleotide - genetics

Aged

Biomarkers, Tumor - genetics

DNA, Neoplasm - genetics

Details

Title: Subtitle: 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
Creators: Jennifer D Brooks - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 307 E 63rd Street, 3rd Floor, New York, NY, USA. brooksj@mskcc.org
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
WECARE Study Collaborative Group
Resource Type: Journal article
Publication Details: Cancer causes & control, Vol.24(8), pp.1605-1614
DOI: 10.1007/s10552-013-0237-6
PMID: 23775025
PMCID: PMC3709075
NLM abbreviation: Cancer Causes Control
ISSN: 0957-5243
eISSN: 1573-7225
Publisher: Netherlands
Grant note: R01 CA129639 / NCI NIH HHS R03 CA139583 / NCI NIH HHS P30 ES005605 / NIEHS NIH HHS U01 CA083178 / NCI NIH HHS R03CA139583 / NCI NIH HHS R01CA097397 / NCI NIH HHS R01 CA097397 / NCI NIH HHS K05 CA136967 / NCI NIH HHS P30 CA008748 / NCI NIH HHS
Language: English
Date published: 08/2013
Academic Unit: Epidemiology
Record Identifier: 9983996091602771

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