ESR1 gene variants affect FSHR-depended risk of fibrocystic mastopathy in infertile women.

Abstract

The infertile women have an increased risk of developing benign and malignant tumors, in particular, breast cancer. Most studies have examined the role of gene variants in the risk of developing breast cancer, but there is little evidence of genetic risk factors for benign tumors. To assess the combined genetic risk of developing mastopathy in women with FSHR (rs6165, rs6166) and ESR1 (rs9340799, rs2234693) gene variants. The study included 87infertile women (45with concomitant fibrocystic mastopathy and 42without mastopathy). For rs9340799and rs2234693variants of the ESR1gene, we did not find any significant differences in the distribution of genotypes in infertile women with or without mastopathy. In patients with mastopathy, there was a reliable increase in the frequency of 307Ala/Ala and 680Ser/Ser genotypes of FSHR gene (χ2= 6.39, p= 0.012, OR= 4.49 (1.48-13.65)) as compared to patients without mastopathy. In the presence of 307Thr/Thr and 680Asn/Asn genotypes of the FSHR gene, a 4.88-fold reduction of mastopathy risk (χ2= 8.06, p= 0.005, OR= 0.21(0.07-0.59)) was observed. The frequency of the FSHR and the ESR1genotypes combinations- 307Thr/Thr+680Asn/Asn+351AG+397TC was significantly decreased in patients with mastopathy. Our study did not find an association of ESR1gene variants with the risk of developing of mastopathy in infertile women although heterozygous variants of the ESR1gene enhanced the "protective" effect of FSHR gene variants and reduced the risk of mastopathy.