Genetic variations in the HIF1A gene modulate response to adjuvant chemotherapy after surgery in patients with colorectal cancer.

BACKGROUND: Hypoxia-inducible factor 1α (HIF-1α) plays an important role in regulating cell survival and angiogenesis, which are critical for tumor growth and metastasis. Genetic variations of HIF1A have been shown to influence the susceptibility to many kinds of human tumors. Increased expression of HIF-1α has also been demonstrated to be involved in tumor progression. However, the prognostic value of single nucleotide polymorphisms (SNPs) in the HIF1A gene remains to be determined in most cancer types, including colorectal cancer (CRC). In this study, we sought to investigate the predictive role of HIF1A SNPs in prognosis of CRC patients and efficacy of chemotherapy. MATERIALS AND METHODS: We genotyped two functional SNPs in HIF1A gene using the Sequenom iPLEX genotyping system and then assessed their associations with clinicopathological parameters and clinical outcomes of 697 CRC patients receiving radical surgery using Cox logistic regression model and Kaplan Meier curves. RESULTS: Generally, no significant association was found between these 2 SNPs and clinical outcomes of CRC. In stratified analysis of subgroup without adjuvant chemotherapy, patients carrying CT/TT genotypes of rs2057482 exhibited a borderline significant association with better overall survival when compared with those carrying CC genotype [Hazard ratio (HR), 0.47; 95% confidence interval (95% CI): 0.29-0.76; P < 0.01]. Moreover, significant protective effects on CRC outcomes conferred by adjuvant chemotherapy were exclusively observed in patients carrying CC genotype of rs2057482 and in those carrying AC/CC genotype of rs2301113. CONCLUSIONS: Genetic variations in HIF1A gene may modulate the efficacy of adjuvant chemotherapy after surgery in CRC patients.

[Preparation of the monoclonal antibodies against human BORIS and the expression pattern of BORIS in normal and diseased human mammary tissues].

AIM: To prepare monoclonal antibodies(mAb) to BORIS antigen and analyze its expression pattern in breast cancer, benign breast disease and normal breast tissues. METHODS: Female BALB/c mice were immunized with recombination human BORIS protein. Hybridoma cell lines were established by hybridoma technique. BORIS antigen was detected by immunohistochemical (ICH) staining. RESULTS: Four clones of hybridomas stably secereting mAb against human BORIS were obtained. mAb FMMU-BORIS13 was selected to be employed in ICH. Positive staining was localized in the nuclei of the spermatocytes and spermatogoniums, which was consistent with the typical expression pattern of CT antigen. BORIS antigen was detected in 85%(94/110) of breast cancer, 95%(21/22) of benign breast diseases and 6 normal breast tissues(surrouding tumor free breast tissue). CONCLUSION: Four clones of anti-BORIS mAb have been successfully prepared. The expression of BORIS antigen is much stronger in breast cancer than that in benign breast disease and normal breast tissues, which indicate that BORIS may be involved in the pathogenesis of the breast cancer.