CYP2D6 *10基因型与接受他莫昔芬治疗的乳腺癌患者生存率之间的关联。

Association between CYP2D6 *10 genotype and survival of breast cancer patients receiving tamoxifen treatment.

作者信息

Xu Y, Sun Y, Yao L, Shi L, Wu Y, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, He L, Li P, Xie Y

机构信息

Breast Center.

Department of Traditional Chinese Medicine, Beijing Cancer Hospital & Institute, Peking University School of Oncology, Beijing, People's Republic of China.

出版信息

Ann Oncol. 2008 Aug;19(8):1423-1429. doi: 10.1093/annonc/mdn155. Epub 2008 Apr 11.

DOI:10.1093/annonc/mdn155

PMID:18407954

Abstract

BACKGROUND

Human cytochrome P450 2D6 (CYP2D6) genotype may affect the efficacy of tamoxifen treatment in Caucasian women with breast cancer. The most common polymorphism of CYP2D6 in Chinese women is variant 10 (188 C to T).

PATIENTS AND METHODS

Tamoxifen and 4-hydroxytamoxifen (4OHtam) were measured in the serum of 37 women with breast cancer who were receiving tamoxifen treatment. The association between CYP2D6 *10 genotype and survival was determined in a cohort of 293 women with breast cancer who received tamoxifen (n = 152) or who did not (n = 141).

RESULTS

The serum 4OHtam concentrations were significantly lower in women with the CYP2D6 *10 homozygous variant T/T genotype than in those with the homozygous wild-type C/C genotype (P = 0.04). Among tamoxifen-treated women, women with the T/T genotype had a significantly worse disease-free survival (DFS) than those with the C/C or C/T genotype, and the T/T genotype remained an independent prognostic factor of DFS in multivariate analysis (hazard ratio = 4.7; 95% confidence interval = 1.1-20.0; P = 0.04). Among women who did not receive tamoxifen, there was no significant association between CYP2D6 *10 genotype and survival.

CONCLUSION

In tamoxifen-treated patients, women with the CYP2D6 *10 T/T genotype have a lower 4OHtam level in the serum and a worse clinical outcome.

摘要

背景

人类细胞色素P450 2D6（CYP2D6）基因型可能会影响白人乳腺癌女性患者他莫昔芬治疗的疗效。中国女性中CYP2D6最常见的多态性是10型变异（188C突变为T）。

患者与方法

检测了37名接受他莫昔芬治疗的乳腺癌女性患者血清中的他莫昔芬和4-羟基他莫昔芬（4OHtam）。在293名接受他莫昔芬治疗（n = 152）或未接受他莫昔芬治疗（n = 141）的乳腺癌女性队列中，确定了CYP2D6 *10基因型与生存率之间的关联。

结果

CYP2D6 *10纯合变异T/T基因型的女性血清4OHtam浓度显著低于纯合野生型C/C基因型的女性（P = 0.04）。在接受他莫昔芬治疗的女性中，T/T基因型的女性无病生存期（DFS）明显差于C/C或C/T基因型的女性，并且在多变量分析中，T/T基因型仍然是DFS的独立预后因素（风险比 = 4.7；95%置信区间 = 1.1 - 20.0；P = 0.04）。在未接受他莫昔芬治疗的女性中，CYP2D6 *10基因型与生存率之间无显著关联。