@article{54d9393a2dc44fde9aa3ab344cbc3a40,
title = "Germline genetic variants in ABCB1, ABCC1 and ALDH1A1, and risk of hematological and gastrointestinal toxicities in a SWOG Phase III trial S0221 for breast cancer",
abstract = "Hematological and gastrointestinal toxicities are common among patients treated with cyclophosphamide and doxorubicin for breast cancer. To examine whether single-nucleotide polymorphisms (SNPs) in key pharmacokinetic genes were associated with risk of hematological or gastrointestinal toxicity, we analyzed 78 SNPs in ABCB1, ABCC1 and ALDH1A1 in 882 breast cancer patients enrolled in the SWOG trial S0221 and treated with cyclophosphamide and doxorubicin. A two-SNP haplotype in ALDH1A1 was associated with an increased risk of grade 3 and 4 hematological toxicity (odds ratio=1.44, 95% confidence interval=1.16-1.78), which remained significant after correction for multiple comparisons. In addition, four SNPs in ABCC1 were associated with gastrointestinal toxicity. Our findings provide evidence that SNPs in pharmacokinetic genes may have an impact on the development of chemotherapy-related toxicities. This is a necessary first step toward building a clinical tool that will help assess risk of adverse outcomes before undergoing chemotherapy.",
keywords = "ALDH1A1, breast cancer, chemotherapy, pharmacogenetics, pharmacokinetics, toxicity",
author = "S. Yao and Sucheston, {L. E.} and H. Zhao and Barlow, {W. E.} and G. Zirpoli and S. Liu and Moore, {H. C.F.} and {Thomas Budd}, G. and Hershman, {D. L.} and W. Davis and Ciupak, {G. L.} and Stewart, {J. A.} and C. Isaacs and Hobday, {T. J.} and M. Salim and Hortobagyi, {G. N.} and Gralow, {J. R.} and Livingston, {R. B.} and Albain, {K. S.} and Hayes, {D. F.} and Ambrosone, {C. B.}",
note = "Funding Information: We thank Dr Frank L. Meyskens, Jr, M.D., Associate Chair for the Cancer Control & Prevention Committee of the Southwest Oncology Group, for his administrative support. This study was supported by NIH R01 CA116395, and the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA63844, CA63845, CA 20319, CA46282, CA46441, CA35261, CA63848, CA67575, CA14028, CA35281, CA128567, CA45560, CA58882, CA13612; CA46368, CA45808, CA58658, CA76447, CA37981, CA04919; CA95860; CA27057, CA42777, CA22433, CA74647, CA86780, CA68183, CA58861, CA45807, CA35192, CA35178, CA58416, CA35176, CA67663, CA35431, CA12644, CA16385, CA11083, CA45377, CA35128, CA35262, CA52654, CA76429, CA58723, CA46113, CA76132, CA45450, CA35119, CA45461, CA21115, CA21076, CA77597, CA25224, CA77202, CCSRI15469, and in part by Amgen. Support was also provided by the Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on Sale (DFH), and Drs Ambrosone, Gralow, Hayes, Hershman and Hortobagyi are recipients of funding from the Breast Cancer Research Foundation. Funding agencies had no involvement in the study design, data collection, analysis and interpretation, or in the writing of the report and submission.",
year = "2014",
month = jun,
doi = "10.1038/tpj.2013.32",
language = "English (US)",
volume = "14",
pages = "241--247",
journal = "Pharmacogenomics Journal",
issn = "1470-269X",
publisher = "Nature Publishing Group",
number = "3",
}