Single nucleotide polymorphisms (SNPs) in the coding sequence of follicle stimulating hormone receptor (FSHR) are associated with ovarian cancer susceptibility

Abstract

Background: Follicle stimulating hormone (FSH) and its receptor (FSHR) are important in ovarian functions and may implicate in ovarian carcinogenesis. Single nucleotide polymorphism (SNP) of the FSHR gene has previously been found to affect FSH efficacy. The objective of this study was to investigate possible association between two SNPs of FSHR gene, Ala307Thr and Ser680Asn, and susceptibility to ovarian cancer. Methods: After histological review, genomic DNA was extracted from non-cancer tissue of 203 ovarian-cancer patients and 267 age-matched control subjects who had surgery for benign gynecological lesions. The genotypes at Ala307Thr and Ser680Asn were assessed by restriction fragment length polymorphism (RFLP) assay. Results: Genotype frequencies were as listed in the table. The genotypes were in Hardy-Weinburg equilibrium for the control group. Homozygous Thr/Thr for SNP Ala307Thr and Asn/Asn for SNP Ser680Asn seem to carry lower risk of ovarian cancer (OR=0.66; 95%CI=0.45-0.96; p=0.030 and OR=0.60; 95%CI=0.41-0.86; p=0.007 respectively). The protective effect was more pronounced for ovarian cancer of serous (OR=0.43; 95%CI=0.24-0.77; p=0.004 for SNP Ala307Thr; OR=0.43; 95%CI=0.24-0.76; p=0.004 for SNP Ser680Asn) and mucinous (OR=0.40; 95%CI=0.18-0.89; p=0.030 for SNPAla307Thr; OR=0.24; 95%CI=0.10-0.56; p<0.001 for SNP Ser680Asn) types. Interestingly, no association was found between these two SNPs with ovarian cancer of endometrioid and clear cell types. Preliminary analysis of FSHR mRNA and protein expression on different histological types of ovarian cancers by reverse transcription (RT)-PCR and immunohistochemistry showed that expression was found in serous and mucinous types of ovarian cancers but not the endometrioid and clear cell carcinomas. Conclusions: Our results suggest that SNPs at these two sites may affect FSHR function and the susceptibility of the women to ovarian cancer. Serous and mucinous ovarian cancer may adopt different carcinogenetic pathways when compared with endometrioid and clear cell carcinomas known to be associated with endometriosis. The possibility of linkage disequilibrium of these two SNPs in Chinese and their effect in combination are being assessed.