| Objective:Endometrial carcinoma (EC) is one of the three common female genital cancers prevalent in the developed countries. Its incidence ranks first among other gynecologic malignancies in the developed country, while in China its incidence follows after that of cervical cancer, but it has shown a rising trend in the recent years. Biological behaviors of malignant tumors are closely related to the specific molecular mechanism and energy metabolism. Nearly50years ago it has been postulated that lipids can be synthesized in tumor tissues, in a manner similar to embryonic tissue. Fatty acid synthesis is a very significant for tumorigenesis and rapid increase in cellular lipids is an essential marker of proliferating tumor cells. Also almost90%of fatty acids synthesized by tumor cells is through the de novo synthesis which is not in any manner influenced or regulated by the fatty acid synthesis in normal cells. Sterol regulatory element binding protein (SREBP) encoded by the SREBF-1gene, is a major regulating factor of lipogenic genes. It activates the transcription of the target genes by binding to the lipid synthase gene promoter/enhancer of the sterol regulatory element (SRE), thus regulating the synthesis as well as metabolism of cholesterol and lipids. Studies have confirmed that SREBP-1is overexpressed in endometrial carcinoma, and the level of its expression depends on the degree of tumor differentiation, SREBP-1shRNA has been found to reduce endometrial cancer cell proliferation, invasion and colony formation and induce apoptosis and inhibit tumorigenesis in nude mice, indicating that endogenous SREBP-1is involved in the development and progression of endometrial cancer. Obesity and diabetes are the established risk factors of endometrioid carcinoma. Studies have shown that SREBF-1gene polymorphism is closely associated with obesity and type II diabetes. Therefore, we hypothesize that SREBF-1gene polymorphism may also be linked with higher risk of endometrioid carcinoma.Methods:Samples were collected from30patients with endometrial carcinoma and6cases with normal endometrium. SREBF-1gene sequence was detected in each sample using the high-throughput sequencing technology. Based on the findings of the study obtained, a specific locus SNP (rs2297508) was selected a clinical case-control study was conducted which included122cases of endometrioid carcinoma and the129cases of benign control. The tissue samples used were all verified by experienced pathologists, and then the total DNA was extracted using a DNA extraction kit, finally the nucleotides were sequenced by RT-PCR analysis.Results:(1) The gene sequence analysis of SREBF-1gene revealed the presence of10SNP loci that could be associated with development, and progression of endometrioid carcinoma, including the three newly discovered ones. The association between the10SNPs and endometrioid carcinoma was substantial.(2)15.1%of endometrial cancer samples had C allele at the locus rs2297508, whereas only7.8%of the benign control had C allele at that locus (p=0.017, OR=2.131). C allele was found to be correlated with endometrial cancer grade (p<0.05) and myometrial invasion (p<0.05).Conclusions:(1) SREBF-1gene possesses10SNP loci that might be associated with the development of endometrioid carcinoma. This has build a new theoretical foundation on which further research with expanded sample size could be undertaken that will take us a step closer to the molecular targeted therapy of endometrioid carcinoma.(2) C allele at SNP (rs2297508) of SREBF-1gene increases the risk of endometrioid carcinoma, and also increases the chances of higher histological grade and deeper myometrial invasion in patients with endometrioid carcinoma, suggesting that SNP (rs2297508) of SREBF-1gene could be regarded as genetic marker of endometrioid carcinoma, thus the screening of the locus alleles might contribute to an early detection of endometrial cancer. |
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