Abstract:

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