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CYP2D6 10和CYP2C19 2、3的基因多态性与接受辅助他莫昔芬治疗的日本乳腺癌患者的预后、子宫内膜厚度或骨密度无关。

Genetic polymorphisms of CYP2D6 10 and CYP2C19 2, 3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen.

作者信息

Okishiro Masatsugu, Taguchi Tetsuya, Jin Kim Seung, Shimazu Kenzo, Tamaki Yasuhiro, Noguchi Shinzaburo

机构信息

Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

出版信息

Cancer. 2009 Mar 1;115(5):952-61. doi: 10.1002/cncr.24111.

Abstract

BACKGROUND

The authors investigated the impact of the genetic polymorphisms cytochrome P450 (CYP) family 2, subfamily D, polypeptide 6, allele 10 (CYP2D6 10) and CYP family 2, subfamily C, polypeptide 19, allele 2, 3 (CYP2C19 2, 3) on disease recurrence in patients with breast cancer who received adjuvant tamoxifen and evaluated the impact of those polymorphisms on endometrial thickness, bone mineral density (BMD), and serum total cholesterol levels.

METHODS

Patients with primary breast cancer (n=173) who had hormone receptor-positive tumors and who also received adjuvant tamoxifen were included in the current study. Genetic polymorphisms of CYP2D6 10 and CYP2C19 2, 3 were analyzed.

RESULTS

Recurrence-free survival (RFS) rates did not differ significantly between patients with the CYP2D6 10/10 genotype (n=40) and patients with the CYP2D6 wild-type (wt)/wt or wt/10 genotype (n=133) or between patients with the CYP2C19 2/2, 2/3, or 3/3 genotypes (n=41) and patients with the CYP2C19 wt/wt, wt/2, or wt/3 genotype (n=132). Multivariate analysis indicated that, even after adjustment for well established prognostic factors, these CYP2D6 or CYP2C19 genotypes were not associated significantly with the RFS rate. Moreover, these genotypes did not affect endometrial thickness, BMD, or total cholesterol levels 1 year after the start of tamoxifen treatment.

CONCLUSIONS

Neither the CYP2D6 10/10 genotype nor the CYP2C19 genotype is likely to have a clinically significant impact on prognosis, endometrial thickness, BMD, or total cholesterol levels in Japanese patients with breast cancer who are treated with adjuvant tamoxifen.

摘要

背景

作者研究了细胞色素P450(CYP)2D亚家族6基因第10等位基因(CYP2D6 10)和CYP2C亚家族19基因第2、3等位基因(CYP2C19 2, 3)的基因多态性对接受他莫昔芬辅助治疗的乳腺癌患者疾病复发的影响,并评估了这些多态性对子宫内膜厚度、骨密度(BMD)和血清总胆固醇水平的影响。

方法

本研究纳入了173例原发性乳腺癌患者,这些患者的肿瘤激素受体呈阳性且接受了他莫昔芬辅助治疗。分析了CYP2D6 10和CYP2C19 2, 3的基因多态性。

结果

CYP2D6 10/10基因型患者(n = 40)与CYP2D6野生型(wt)/wt或wt/10基因型患者(n = 133)之间的无复发生存(RFS)率无显著差异,CYP2C19 2/2、2/3或3/3基因型患者(n = 41)与CYP2C19 wt/wt、wt/2或wt/3基因型患者(n = 132)之间的RFS率也无显著差异。多变量分析表明,即使在对已确定的预后因素进行调整后,这些CYP2D6或CYP2C19基因型与RFS率也无显著相关性。此外,这些基因型在他莫昔芬治疗开始1年后不影响子宫内膜厚度、骨密度或总胆固醇水平。

结论

对于接受他莫昔芬辅助治疗的日本乳腺癌患者,CYP2D6 10/10基因型和CYP2C19基因型均不太可能对预后、子宫内膜厚度、骨密度或总胆固醇水平产生临床显著影响。

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