Colorectal Cancer Risk in Relation to Hypoxia Inducible Factor-1α (Hif-1 α) and Von Hippel-Lindau (Vhl) Gene Polymorphisms

[摘要] Colorectal cancers (CRC) are among the four most frequently seen cancers in humans and are the second leading cause of cancer- related deaths. Hypoxia up regulates multiple genes involved in different steps of metastatic process, including angiogenesis, proliferation, migration, invasion, motility, adhesion and survival. Hypoxia Inducible Factor 1 (HIF-1) is a master regulator protein of cellular hypoxia-response and triggers the expression of above-mentioned metastatic-process genes. Von Hippel Lindau (VHL) is a protein that plays critical role in the response to hypoxia and product of a tumor suppressor gene. We studied three single nucleotide polymorphisms, rs11549465 (1772C > T), rs11549467 (1790G > A) in HIF-1α and rs779805 (5’UTR A > G) in VHL, and assessed their associations with CRC risk, clinicopathologic and demographic features and lifestyle, and tumor stage and grade of CRC patients and/or healthy controls. ARMS-PCR technique for genotyping of rs11549465 C > T and rs11549467 G>A and PCR-RFLP technique for genotyping of rs779805 A>G were used. CT/TT genotypes of HIF-1α 1772C > T polymorphism were found to increase the risk of colorectal cancer in patients (OR= 1.96, 95% CI= 1.02-3.77, p< 0.05). Additionally, it was demonstrated via statistical analyses that higher age, male gender, cancer history in family, co-existing diseases, and exposure to white soil stands to be risk factors of colorectal cancer (p< 0.05). No significant relation was found between patient’s TNM stages and distributions of genotype (p> 0.05). The findings from our study demonstrates that, in addition to risk factors for colorectal cancer, scanning CT/TT genotypes of HIF-1α C1772T polymorphism can be advantageous in early-diagnosis of colorectal cancer.

[学科分类] 肿瘤学

[关键词] Colorectal cancer;HIF-1αVHL;rs11549465;rs11549467