Abstract
Ovarian cancer (OC) is one of the most common gynecologic cancers,with significant morbidity and mortality. The risk of OC is influenced by hormone status, of which sex hormone-binding globulin (SHBG), which influences the serum availability of steroid sex hormones, is implicated in the pathogenesis and evolution of OC. The aim of this study is to evaluate the involvement of common SHBG gene variants in OC susceptibility and evolution. A case control study including 71 OC patients and 74 cancer-free controls, who were genotyped for rs9898876, rs13894, rs1799941 and rs6257 SHBG SNP. Genotyping was done by the allelic discrimination method, using VIC- and FAM-labeled primers. The minor allele frequencies of rs9898876, rs13894, rs1799941 and rs6257 SHBG SNP was comparable between OC cases and control women, implying no significant associations of the tested variants and overall OC risk. Taking homozygous wild-type genotype as reference (OR = 1.00), heterozygous rs9898876 (G/T), and minor allele-carrying genotypes [G/T + T/T] were associated with reduced risk of OC. While rs9898876 heterozygosity (G/T) was predictive of OC occurrence, no significant association of the remaining three tested SNPs was noted with altered risk of OC. Irrespective of FIGO staging, the four tested SHBG SNPs were not associated with the clinical progression of OC. In conclusion, SHBG rs9898876 is associated with a decreased risk of OC, and thus constitutes a potential diagnostic biomarker of OC.
Highlights
Ovarian cancer (OC) is a significant gynecological malignancy, and accounts about 2.5% of all malignancies among women, and 5% of deaths of female cancers [1]
The risk of OCis influenced by hormone status, of which sex hormone-binding globulin (SHBG), whichinfluences the serum availability of steroid sex hormones, is implicated in the pathogenesis and evolution of OC
The minor allele frequencies of rs9898876, rs13894, rs1799941 and rs6257 SHBG SNP was comparable between OC cases and control women, implying no significant associations of the tested variants and overall OC risk
Summary
Ovarian cancer (OC) is a significant gynecological malignancy, and accounts about 2.5% of all malignancies among women, and 5% of deaths of female cancers [1]. Two major theories were proposed for the pathogenesis of OC, namely the incessant ovulation, and the gonadotropin connection [5, 6] Both epidemiologic and experimental evidence support the contribution of altered steroid sex hormone balance to the pathogenesis of OC, acting through stimulation of cell proliferation and telomerase expression. These in turn precipitate angiogenesis and greatly enhance carcinogenesis and metastasis, principally through the PI3K/AKT pathway[7, 8].In support of the role of sex hormones in enhanced risk of OC was the findings thataltered serum levels of circulating steroid sex hormones increase the overall incidence of OC [6, 7, 9], and that women on hormone replacement therapy are at increased risk for OC development [10]. Genotyping was done by the allelic discrimination method, using VIC- and FAM-labeled primers
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