Lessons for pharmacogenomics studies: association study between CYP2D6 genotype and tamoxifen response.
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.
Kiyotani
Kazuma
K
Laboratory for Pharmacogenetics, RIKEN Center for Genomic Medicine, Yokohama, Japan.
Mushiroda
Taisei
T
Hosono
Naoya
N
Tsunoda
Tatsuhiko
T
Kubo
Michiaki
M
Aki
Fuminori
F
Okazaki
Yutaka
Y
Hirata
Koichi
K
Takatsuka
Yuichi
Y
Okazaki
Minoru
M
Ohsumi
Shozo
S
Yamakawa
Takashi
T
Sasa
Mitsunori
M
Nakamura
Yusuke
Y
Zembutsu
Hitoshi
H
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*
D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6