Follicle-Stimulating Hormone Receptor Polymorphisms and Its Association with Ovarian Carcinoma

Objectives: Follicle stimulating hormone (FSH) and its receptor (FSHR) are
important in ovarian follicular development and can influence the growth of ovarian
epithelial cells. It seems to implicate in ovarian carcinogenesis. Thr307Ala and
Asn680Ser are two single nucleotide polymorphisms (SNPs) of the FSHR gene which
have effects on FSH efficacy. Our aim was to examine the association between these
two SNPs of FSHR gene and the risk of epithelial ovarian carcinoma in Egyptian
females. Subjects and Methods: Genomic DNA was extracted from 40
histopathologically confirmed ovarian cancer patients and 20 cancer-free control
subjects using Polymerase chain reaction (PCR) assays with restriction
fragment length polymorphism (RFLP). Results: showed a non-significant association
between the genotypes with tumor stage for SNPs Ala307Thr and Ser680Asn
(P>0.05). The 307Ala and 680Ser carriers had higher risk to develop ovarian cancer
when compared with the controls (X2=3.935,,P =0.047, OR =2.81, 95% CI =0.99–
8.02; and X2=5.26, P=0.022, OR=3.491, 95% CI =1.158–10.526,respectively). The
genotypes of the two SNPs were significantly associated with the serous (SC) and
mucinous (MC) subtypes (X2=15.597, P=0.000 and X2=19.858, P = 0.000,
respectively), with non-significant associations in endometrioid (EC) and clear cell
(CC) subtypes (P>0.05). The two SNPs were found to be in modest linkage
disequilibrium, D 0.182 = ׳ and 0.1, r2 = 0.553 and 0.333 for the cancer and control
groups, respectively. Haplotype Ala307-Ser680 was shown to be associated with
higher risk of ovarian cancer (X2=5.79, P=0.026, OR=0.303, 95% CI =0.111–0.825),
with more association with SC and MC subtypes (X2=0.213, P= 0.002, OR = 0.184,
95% CI =0.062–0.543), in the EC and CC subtypes this haplotype showed no
significant correlation (P>0.05). Conclusion: SNPs at these two sites of FSHR may
influence FSHR function and enhance the probability to specific subtypes of ovarian
cancer. They may be useful as a DNA-based diagnostic biomarker for identifying
high-risk Egyptian females susceptible to ovarian cancer. SC and MC ovarian cancer
may have different carcinogenetic pathways when compared with EC and CC
carcinomas in Egyptian females.