Rs1008805 Polymorphism In The Cyp19a1 Gene Is Related To The Prognosis Of Stage I-Ii And Operable Stage Iii Breast Cancer

Purpose Aromatase, encoded by CYP19A1 gene, is a rate-limiting enzyme in the conversion of androgens into estrogens. It has been demonstrated that genetic polymorphisms in CYP19A1 gene were significantly correlated with altered hormone levels in urine and serum, providing an explication for an elevated risk for progression in relation with increasing estrogen exposure. Consequently, it is biologically plausible that CYP19A1 gene polymorphisms may be related to the prognosis of breast cancer. Methods CYP19A1 gene rs1008805 polymorphism were genotyped on 406 Chinese Han women with stage I-II and operable stage III breast cancer. Associations were evaluated between CYP19A1 rs1008805 genotypes and disease-free survival (DFS). Results Totally, there were 200 (49.3%) patients with AA genotype, 169 (41.6%) with AG variant, and 37 (9.1%) carrying GG variant. No significant differences were found in DFS among the whole population with these three genotypes. However, postmenopausal women with GG variant had a poorer DFS when compared with those carrying AG or AA genotype (13.7 months versus 56.3 months; HR, 2.462; 95 % CI, 1.310-4.628; P = 0.004). And what9s more, being adjusted by patients features in multivariate analyses, GG genotype remained an independent prognostic factor for DFS (HR, 2.706; 95 % CI, 1.393-5.257; P = 0.003). Premenopausal women with GG variant had a marginally improved DFS when compared with those carrying AG or AA genotypes (87.0 months versus 48.7 months; HR, 0.544; 95% CI, 0.295-1.003; P = 0.051). However, this difference was not confirmed by multivariate analyses. Conclusions The present study indicated that GG genotype of rs1008805 SNP in the first exon of CYP19A1 gene was significantly related to a worse DFS in postmenopausal women with early breast cancer. This founding is novel, if confirmed, CYP19A1 rs1008805 genotypes may turn to be a prognostic biomarker for early breast cancer. Citation Format: Shao X, Zheng Y, Shi L, Huang Y, Wang X. Rs1008805 polymorphism in the CYP19A1 gene is related to the prognosis of stage I–II and operable stage III breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-03-19.