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

Abstract

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. IntroductionOver the last three decades, the number of breast cancer cases has increased worldwide (1) to become the most likely cause of cancer mortality and morbidity in females (2). Increased levels of aromatase expression have been observed in breast lesions compared with normal breast tissue (3,4) and alterations in aromatase expression are associated with the pathogenesis of breast cancer (5,6).Approximately two thirds of breast cancer cases overexpress estrogen receptors (ER) and/or progesterone receptors (PgR) (7,8). Consequently, endocrine therapy, including tamoxifen or aromatase inhibitors (AIs), has become an effective treatment for these patients. For decades, 5-year tamoxifen administration was the gold standard for the adjuvant endocrine treatment of breast cancer (9). More recently, postmenopausal patients have also had the option of receiving AIs as an alternative to tamoxifen, or following tamoxifen treatment (10). The presence and intensity of ER and/or PgR are useful predictive markers for the response to hormone therapy in clinica...

CYP19A1 Is Regulated by BRD4 and Suppresses Castration-resistant Prostate Cancer Cell Invasion and Proliferation by Decreasing AR Expression

“…Therefore, the higher the expression of CYP19A1, the lower the androgen level in serum. In addition, CYP19A1 has been demonstrated to play an important role in the occurrence of breast cancer and even affect patients' survival [31]. Various drugs can inhibit the function of CYP19A1, such as Letrozole, have been used in clinical settings to treat breast cancer [32].…”