Variants in tamoxifen metabolizing genes: A case-control study of contralateral breast cancer risk in the WECARE study Journal Article


Authors: Brooks, J. D.; Teraoka, S. N.; Malone, K. E.; Haile, R. W.; Bernstein, L.; Lynch, C. F.; Mellemkjær, L.; Duggan, D. J.; Reiner, A. S.; Concannon, P.; Schiermeyer, K.; Lewinger, J. P.; Bernstein, J. L.; Figueiredo, J. C.
Article Title: Variants in tamoxifen metabolizing genes: A case-control study of contralateral breast cancer risk in the WECARE study
Abstract: Tamoxifen has been shown to greatly reduce risk of recurrence and contralateral breast cancer (CBC). Still, second primary contralateral 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.
Keywords: adult; controlled study; aged; major clinical study; single nucleotide polymorphism; cancer risk; breast cancer; genetic variability; genotype; enzyme activity; brca1 protein; brca2 protein; risk factor; single nucleotide polymorphisms; blood sampling; atm protein; tamoxifen; interview; contralateral breast cancer
Journal Title: International Journal of Molecular Epidemiology and Genetics
Volume: 4
Issue: 1
ISSN: 1948-1756
Publisher: e-Century Publishing Corporation  
Date Published: 2013-01-01
Start Page: 35
End Page: 48
Language: English
PROVIDER: scopus
PMCID: PMC3612453
PUBMED: 23565321
DOI/URL:
Notes: --- - "Export Date: 1 May 2013" - ": Chemicals/CAStamoxifen, 10540-29-1" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Anne S Reiner
    248 Reiner
  2. Jonine L Bernstein
    142 Bernstein
  3. Jennifer Brooks
    17 Brooks