Rs1008805 polymorphism of CYP19A1 gene is associated with the efficacy of hormone therapy in stage I-II and operable stage III breast cancer

Xiying Shao; Lei Luo; Yong Guo; Xiaohong Xu; Dehou Deng; Jianguo Feng; Yuheng Ding; Hanzhou Mou; Ping Huang; Lei Shi; Yuan Huang; Weiwu Ye; Caijin Lou; Zhanhong Chen; Yabing Zheng; Xiaojia Wang

doi:10.3892/ol.2017.6984

Rs1008805 polymorphism of CYP19A1 gene is associated with the efficacy of hormone therapy in stage I-II and operable stage III breast cancer

Oncol Lett. 2017 Nov;14(5):6156-6162. doi: 10.3892/ol.2017.6984. Epub 2017 Sep 18.

Authors

Xiying Shao¹, Lei Luo², Yong Guo³, Xiaohong Xu⁴, Dehou Deng¹, Jianguo Feng⁵, Yuheng Ding³, Hanzhou Mou⁵, Ping Huang¹, Lei Shi¹, Yuan Huang¹, Weiwu Ye¹, Caijin Lou¹, Zhanhong Chen¹, Yabing Zheng¹, Xiaojia Wang¹

Affiliations

¹ Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
² Zhejiang Institute for Food and Drug Control, Hangzhou, Zhejiang 310052, P.R. China.
³ Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Traditional Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.
⁴ Clinical Laboratory, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
⁵ Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.

Abstract

It has been hypothesized that single nucleotide polymorphisms in CYP19A1 gene may alter aromatase activity and circulating steroid hormone levels in females. Therefore, it is biologically reasonable that CYP19A1 rs1008805 (A/G) polymorphism may be associated with the clinical outcome of hormone therapy. Genotyping for the CYP19A1 rs1008805 polymorphism was performed for 287 females with hormone receptor (HR)-positive early breast cancer, and potential associations were evaluated between CYP19A1 rs1008805 genotypes and disease-free survival (DFS). Based on the analysis of the whole cohort, no significant differences were observed between rs1008805 genotypes and DFS. However, in postmenopausal females, rs1008805 variants were significantly associated with DFS (AA vs. AG vs. GG, 89.2 vs. 58.2 vs. 32.7 months; P=0.019). In addition, when the population was divided into two cohorts, females with the GG variant exhibited a significantly poorer DFS [GG vs. AA or AG, 32.7 vs. 70.6 months; hazard ratio (HR), 3.613; 95% confidence interval (CI), 1.380-9.457; P=0.005]. Furthermore, when adjusted for other patient features in multivariate analyses, GG genotype remained an independent prognostic marker for DFS (HR, 3.439; 95% CI, 1.251-9.456; P=0.017). However, there were no significant differences in DFS between patients harboring the minor allele and those with the homozygous common allele (AG or GG vs. AA, 52.4 vs. 89.2 months; HR, 1.288; 95% CI, 0.705-2.353; P=0.408). There were also no associations between rs1008805 polymorphism and DFS for premenopausal females. In conclusion, the homozygous minor allele (GG) of CYP19A1 rs1008805 was identified to be significantly associated with an inferior clinical outcome of hormone therapy in postmenopausal hormone receptor-positive patients with early breast cancer. If confirmed by further study, genotyping for CYP19A1 rs1008805 polymorphism may provide predictive information to improve the selection of endocrine treatment.

Keywords: aromatase; breast cancer; cytochrome P450 19A1; polymorphisms; predictive role.