Lessons for pharmacogenomics studies: Association study between CYP2D6 genotype and tamoxifen response

Kazuma Kiyotani, Taisei Mushiroda, Naoya Hosono, Tatsuhiko Tsunoda, Michiaki Kubo, Fuminori Aki, Yutaka Okazaki, Koichi Hirata, Yuichi Takatsuka, Minoru Okazaki, Shozo Ohsumi, Takashi Yamakawa, Mitsunori Sasa, Yusuke Nakamura, Hitoshi Zembutsu

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Abstract

We earlier reported a significant association between the cytochrome P450 2D6 (CYP2D6) genotype and the clinical outcome in 282 Japanese breast cancer patients receiving tamoxifen monotherapy. Although many research groups have provided evidence indicating the CYP2D6 genotype as one of the strongest predictors of tamoxifen response, the results still remain controversial. We hypothesized that concomitant treatment was one of the causes of these controversial results. We then studied 167 breast cancer patients who received tamoxifen-combined therapy to evaluate the effects of concomitant treatment on the association analysis and observed no significant association between CYP2D6 genotype and recurrence-free survival (P=0.44, hazard ratio: 0.64, 95% confidential interval: 0.20-1.99 in patients with two variant alleles vs. patients without a variant allele). When we carried out two subgroup analyses for nodal status and tumor size, we observed a positive association between the CYP2D6 genotype and the clinical outcome only in patients who received tamoxifen monotherapy. This study explained a part of the discrepancies among the reported results.

Original languageEnglish
Pages (from-to)565-568
Number of pages4
JournalPharmacogenetics and genomics
Volume20
Issue number9
DOIs
Publication statusPublished - 01-09-2010

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Kiyotani, K., Mushiroda, T., Hosono, N., Tsunoda, T., Kubo, M., Aki, F., Okazaki, Y., Hirata, K., Takatsuka, Y., Okazaki, M., Ohsumi, S., Yamakawa, T., Sasa, M., Nakamura, Y., & Zembutsu, H. (2010). Lessons for pharmacogenomics studies: Association study between CYP2D6 genotype and tamoxifen response. Pharmacogenetics and genomics, 20(9), 565-568. https://doi.org/10.1097/FPC.0b013e32833af231