Follicle-Stimulating Hormone Receptor Polymorphisms and Its Association with Ovarian Carcinoma | ||
| Bulletin of Egyptian Society for Physiological Sciences | ||
| Article 13, Volume 32, Issue 1, June 2012, Pages 191-206 PDF (305 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/besps.2012.35586 | ||
| Authors | ||
| Amal Mackawy* ; Wafaa Emam | ||
| Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University | ||
| Abstract | ||
| 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. | ||
| Keywords | ||
| FSHR; Single nucleotide polymorphism; ovarian carcinoma predisposition | ||
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