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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2013, Vol. 07 ›› Issue (06) : 406 -410. doi: 10.3877/cma. j. issn.1674-0807.2013.06.003

论著

CYP2D6*10 基因多态性与服用他莫昔芬乳腺癌患者预后的相关性
田超1, 杨义2, 李卉1,†()   
  1. 1.610041 成都,四川省肿瘤医院乳腺科
    2.610041 四川省成都中医药大学管理学院
  • 收稿日期:2013-07-19 出版日期:2013-12-01
  • 通信作者: 李卉
  • 基金资助:
    四川省卫生厅科研项目(110265)

Correlation between CYP2D6*10 gene polymorphism and prognosis of breast cancer patients treated with tamoxifen

Chao TIAN1, Yi YANG1, Hui LI1,†()   

  1. 1.Department of Breast Surgery, Sichuan Provincial Cancer Hospital, Chengdu 610041, China
  • Received:2013-07-19 Published:2013-12-01
  • Corresponding author: Hui LI
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田超, 杨义, 李卉. CYP2D6*10 基因多态性与服用他莫昔芬乳腺癌患者预后的相关性[J/OL]. 中华乳腺病杂志(电子版), 2013, 07(06): 406-410.

Chao TIAN, Yi YANG, Hui LI. Correlation between CYP2D6*10 gene polymorphism and prognosis of breast cancer patients treated with tamoxifen[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2013, 07(06): 406-410.

目的

探讨CYP2D6*10 基因多态性与服用他莫昔芬(TAM)乳腺癌患者预后的相关性。

方法

收集四川省肿瘤医院2008年1月至2010年10月期间200 例服用TAM 的乳腺癌患者的口腔黏膜,采用实时RT-PCR 法检测CYP2D6*10 基因多态性,并分为CYP2D6 突变组(CYP2D6*10/*10)和CYP2D6 正常组(CYP2D6 wt/*10 和CYP2D6 wt/wt)。 采用卡方检验及秩和检验分析CYP2D6*10 基因多态性与临床病理特征的关系,采用Cox 比例风险回归模型分析其与预后的关系。

结果

在200 例乳腺癌中,CYP2D6*10/*10 纯合子94 例(47%),CYP2D6 wt/wt 野生型48 例(24%),CYP2D6 wt/*10 杂合型58 例(29%)。 CYP2D6*10 基因多态性与患者的组织学分级、TNM 分期、HER-2 表达、肿瘤类型无关(Z=-0.444,P=0.674;Z=-0.716,P=0.500;χ2 =0.066,P=0.797;χ2 =0.694,P=0.405)。 Log-rank检验分析显示CYP2D6*10 突变组患者平均无瘤生存时间明显短于CYP2D6*10 正常组患者(47.2 个月比51.2 个月,χ2=5.554,P=0.018)。 Cox 比例风险回归模型显示,CYP2D6*10 基因型与患者无瘤生存时间明显相关(HR=2.755,95%CI:1.230 ～6.173, P=0.014)。

结论

CYP2D6*10/*10 基因型乳腺癌患者服用他莫昔芬预后较差。

关键词: 乳腺肿瘤, 他莫昔芬, 细胞色素P450 CYP2D6, 预后

Objective To investigate the correlation of CYP2D6*10 gene polymorphism with prognosis of breast cancer patients taking tamoxifen.

Methods

The oral mucosa samples were taken from 200 breast cancer patients who received oral administration of tamoxifen from January 2008 to October 2010 in Sichuan Provincial Cancer Hospital. Real-time RT-PCR was used to determine CYP2D6*10 gene polymorphism.According to the results, the patients were divided into two groups: CYP2D6 mutation group(CYP2D6*10/*10)and CYP2D6 normal group(CYP2D6 wt/*10 and CYP2D6 wt/wt). The relationship between CYP2D6*10 gene polymorphism and clinicopathological characteristics was assessed by Chi-square test and rank sum test.Meanwhile, Cox proportional hazards regression model was established to display the prognostic value of CYP2D6*10 gene polymorphism.

Results

Among 200 cases of breast cancer patients, CYP2D6*10/*10 homozygotes were found in 94 cases (47%),CYP2D6 wt/wt wild type in 48 cases (24%) and CYP2D6 wt/*10 heterozygotes in 58 cases (29%). CYP2D6*10 gene polymorphism was not statistically related to histological grade, TNM staging, HER-2 expression, tumor types (Z=-0.444,P=0.674;Z=-0.716,P=0.500;χ2 =0.066,P=0.797;χ2=0.694,P=0.405). Log-rank test showed that the disease-free survival in patients with CYP2D6 mutation was significantly shorter than that in patients without CYP2D6 mutation (mean 47.2 months vs mean 51.2 months,χ2=5.554,P=0.018). Cox proportional hazards regression model showed that CYP2D6*10 genotype was significantly related to the disease-free survival of patients(HR=2.755,95%CI:1.230-6.173,P=0.014).

Conclusion

The breast cancer patients with CYP2D6*10/*10 genotype have a poor prognosis after tamoxifen administration.

Key words: Breast neoplasms, Tamoxifen, Cytochrome P-450 CYP2D6, Prognosis
表1 CYP2D6*10 基因多态性与临床病理特征的关系
CYP2D6基因分型 例数 组织学分级[例(%)] TNM分期[例(%)] HER-2[例(%)] 肿瘤类型[例(%)]
1级 2级 3级 Ⅰ期 Ⅱ期 Ⅲ期 + - 浸润性导管癌 其他
突变组(*10/*10) 94 24(47) 38(49) 32(45) 10(42) 67(48) 17(49) 19(20) 75(80) 82(87) 12(13)
正常组(wt/*10+wt/wt) 106 27(53) 40(51) 39(55) 14(58) 74(52) 18(51) 23(22) 83(78) 88(83) 18(17)
检验值 Z=-0.444 Z=-0.716 χ 2=0.066 χ 2=0.694
P值 0.674a 0.500a 0.797b 0.405b
表2 乳腺癌患者无瘤生存时间的Cox 比例风险回归模型分析
变量 偏回归系数 标准误 Wald统计量 P值 Exp(B)值 相对危险度及95%可信区间
基因型 1.013 0.412 6.065 0.014 2.755 2.755(1.230～6.173)
TNM分期 1.249 0.353 12.497 0.000 3.485 3.485(1.744～6.964)
HER-2 0.830 0.416 3.972 0.046 2.293 2.293(1.014～5.185)
组织学分级 0.764 0.436 3.067 0.080 2.147 2.304(0.913～5.048)
图1 CYP2D6 基因型与乳腺癌预后的关系 P=0.018,CYP2D6 突变组与CYP2D6 正常组比较(χ2=5.554)
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