International Journal of Hematology and Oncology 2021, Vol 31, Num 4 Page(s): 13-20
Colorectal Cancer Risk in Relation to Hypoxia Inducible Factor-1α (Hif-1 α) and Von Hippel-Lindau (Vhl) Gene Polymorphisms

H. Saygin DEMIREL1, Pelin TASDEMIR2, Sumeyra CETINKAYA1, Ilknur CINAR1, Tevfik KUCUKKARTALLAR3, Gul DURSUN1

1Necmettin Erbakan University Meram Faculty of Medicine, Department of Biology, Konya, TURKEY
2Necmettin Erbakan University Meram Faculty of Medicine, Department of Medical Genetics, Konya, TURKEY
3Necmettin Erbakan University Meram Faculty of Medicine, Department of General Surgery, Konya, TURKEY

Keywords: Colorectal cancer, HIF-1α, VHL, rs11549465, rs11549467
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.