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Int J Mol Epidemiol Genet 2013;4(1):35-48
Original Article
Variants in tamoxifen metabolizing genes: a case-control study of contralateral
breast cancer risk in the WECARE study
Jennifer D Brooks, Sharon N Teraoka, Kathleen E Malone, Robert W Haile, Leslie Bernstein, Charles F Lynch, Lene
Mellemkjær, Da-vid J Duggan, Anne S Reiner, Patrick Concannon, Katherine Schiermeyer, Juan Pablo Lewinger, The WECARE
Study Collaborative Group, Jonine L Bernstein, Jane C Figueiredo
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center; University of Florida Genetics Institute
and Depart-ment of Pathology, Immunology and Laboratory Medicine, University of Florida; Program in Epidemiology, Division
of Public Health Science, Fred Hutchinson Cancer Research Center; Stanford School of Medicine, Department of Medicine,
Division of Oncology; Department of Population Sciences, Beckman Research Institute of the City of Hope; Department of
Epidemiology, The University of Iowa College of Public Health; Research Department II, Institute of Cancer Epidemiology,
Danish Cancer Society; Genetic Basis of Human Disease Division, Trans-lational Genomic Research Institute; Department of
Biochemistry and Molecular Genetics, University of Virginia; Department of Preventive Medicine, Norris Comprehensive Cancer
Center, Keck School of Medicine, University of Southern California
Received December 7, 2012; Accepted February 11, 2013; Epub March 18, 2013; Published March 28, 2013
Abstract: Tamoxifen has been shown to greatly reduce risk of recurrence and contralateral breast cancer (CBC). Still, second
primary contra-lateral breast cancer is the most common malignancy to follow a first primary breast cancer. Genetic variants in
CYP2D6 and other drug-metabolizing enzymes that alter the metabolism of tamoxifen may be associated with CBC risk in
women who receive the drug. This is the first study to investigate the impact of this variation on risk of CBC in women who
receive tamoxifen. From the population-based Women’s Environment Cancer and Radiation Epidemiology (WECARE) Study,
we included 624 Caucasian women with CBC (cases) and 1,199 women with unilateral breast cancer (controls) with complete
information on tumor characteristics and treatment. Conditional logistic regression was used to assess the risk of CBC
associated with 112 single nucleotide polymorphisms (SNPs) in 8 genes involved in the metabolism of tamoxifen among
tamoxifen users and non-users. After adjustment for multiple testing, no significant association was observed between any of
the genotyped variants and CBC risk in either tamoxifen users or non-users. These results suggest that when using a tagSNP
approach, common variants in selected genes involved in the metabolism of tamoxifen are not associated with risk of CBC
among women treated with the drug (IJMEG1212003).
Keywords: Contralateral breast cancer, tamoxifen, single nucleotide polymorphisms
Address correspondence to: Jennifer D Brooks, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering
Cancer Center, 307 E 63rd Street, 2nd floor, New York, NY. Tel: 646-735-8068; E-mail: brooksj@mskcc.org
Original Article
Variants in tamoxifen metabolizing genes: a case-control study of contralateral
breast cancer risk in the WECARE study
Jennifer D Brooks, Sharon N Teraoka, Kathleen E Malone, Robert W Haile, Leslie Bernstein, Charles F Lynch, Lene
Mellemkjær, Da-vid J Duggan, Anne S Reiner, Patrick Concannon, Katherine Schiermeyer, Juan Pablo Lewinger, The WECARE
Study Collaborative Group, Jonine L Bernstein, Jane C Figueiredo
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center; University of Florida Genetics Institute
and Depart-ment of Pathology, Immunology and Laboratory Medicine, University of Florida; Program in Epidemiology, Division
of Public Health Science, Fred Hutchinson Cancer Research Center; Stanford School of Medicine, Department of Medicine,
Division of Oncology; Department of Population Sciences, Beckman Research Institute of the City of Hope; Department of
Epidemiology, The University of Iowa College of Public Health; Research Department II, Institute of Cancer Epidemiology,
Danish Cancer Society; Genetic Basis of Human Disease Division, Trans-lational Genomic Research Institute; Department of
Biochemistry and Molecular Genetics, University of Virginia; Department of Preventive Medicine, Norris Comprehensive Cancer
Center, Keck School of Medicine, University of Southern California
Received December 7, 2012; Accepted February 11, 2013; Epub March 18, 2013; Published March 28, 2013
Abstract: Tamoxifen has been shown to greatly reduce risk of recurrence and contralateral breast cancer (CBC). Still, second
primary contra-lateral breast cancer is the most common malignancy to follow a first primary breast cancer. Genetic variants in
CYP2D6 and other drug-metabolizing enzymes that alter the metabolism of tamoxifen may be associated with CBC risk in
women who receive the drug. This is the first study to investigate the impact of this variation on risk of CBC in women who
receive tamoxifen. From the population-based Women’s Environment Cancer and Radiation Epidemiology (WECARE) Study,
we included 624 Caucasian women with CBC (cases) and 1,199 women with unilateral breast cancer (controls) with complete
information on tumor characteristics and treatment. Conditional logistic regression was used to assess the risk of CBC
associated with 112 single nucleotide polymorphisms (SNPs) in 8 genes involved in the metabolism of tamoxifen among
tamoxifen users and non-users. After adjustment for multiple testing, no significant association was observed between any of
the genotyped variants and CBC risk in either tamoxifen users or non-users. These results suggest that when using a tagSNP
approach, common variants in selected genes involved in the metabolism of tamoxifen are not associated with risk of CBC
among women treated with the drug (IJMEG1212003).
Keywords: Contralateral breast cancer, tamoxifen, single nucleotide polymorphisms
Address correspondence to: Jennifer D Brooks, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering
Cancer Center, 307 E 63rd Street, 2nd floor, New York, NY. Tel: 646-735-8068; E-mail: brooksj@mskcc.org
