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

S. Yao, L. E. Sucheston, H. Zhao, W. E. Barlow, G. Zirpoli, S. Liu, H. C.F. Moore, G. Thomas Budd, D. L. Hershman, W. Davis, G. L. Ciupak, J. A. Stewart, C. Isaacs, T. J. Hobday, M. Salim, G. N. Hortobagyi, J. R. Gralow, R. B. Livingston, K. S. Albain, D. F. HayesC. B. Ambrosone

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)241-247
Number of pages7
JournalPharmacogenomics Journal
Volume14
Issue number3
DOIs
StatePublished - Jun 2014

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Keywords

  • ALDH1A1
  • breast cancer
  • chemotherapy
  • pharmacogenetics
  • pharmacokinetics
  • toxicity

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Yao, S., Sucheston, L. E., Zhao, H., Barlow, W. E., Zirpoli, G., Liu, S., Moore, H. C. F., Thomas Budd, G., Hershman, D. L., Davis, W., Ciupak, G. L., Stewart, J. A., Isaacs, C., Hobday, T. J., Salim, M., Hortobagyi, G. N., Gralow, J. R., Livingston, R. B., Albain, K. S., ... Ambrosone, C. B. (2014). 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. Pharmacogenomics Journal, 14(3), 241-247. https://doi.org/10.1038/tpj.2013.32