title: Lessons for pharmacogenomics studies: association study between CYP2D6 genotype and tamoxifen response.
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.
authors.affiliation: Laboratory for Pharmacogenetics, RIKEN Center for Genomic Medicine, Yokohama, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kiyotani
authors.forename: Taisei
authors.initials: T
authors.lastname: Mushiroda
authors.forename: Naoya
authors.initials: N
authors.lastname: Hosono
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Fuminori
authors.initials: F
authors.lastname: Aki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takatsuka
authors.forename: Minoru
authors.initials: M
authors.lastname: Okazaki
authors.forename: Shozo
authors.initials: S
authors.lastname: Ohsumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamakawa
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sasa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Zembutsu
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D010597:Pharmacogenetics; D016016:Proportional Hazards Models; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6