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.

The ratio of second to fourth digit length (2D:4D) and coronary artery disease in a Han Chinese population.

BACKGROUND: The association between index finger to ring finger length ratio (2D:4D) and cardiac disorders has been reported, however it has not been discussed in terms of coronary artery disease (CAD). We investigated whether 2D:4D could be used as a marker for predisposition to CAD as assessed by coronary angiography in Chinese men and women. METHODS: This study included 1764 persons divided into 4 groups, 441 cases with CAD and 441 persons without CAD as control in each sex of the same age. Finger lengths were measured twice for both hands using electronic calipers. Student t test was used to detect the difference of 2D:4D among groups. The receiver operator characteristic curves (ROCs) were used to detect the diagnostic effect of 2D:4D for CAD. RESULTS: There were no significant differences in age among the four groups. A significant difference of 2D:4D ratios between right and left hand were observed only in men in both control and CAD groups. On the right hand in the control group and on both hands in the CAD group, the 2D:4D ratios were higher in women than in men (all, P < 0.001). In men with CAD, mean 2D:4D was higher than mean 2D:4D in control men (right hand 0.962±0.042:0.927±0.038; left hand 0.950±0.044:0.934±0.048; both hands, P < 0.001), but this was not observed in women. No relationship was found between 2D:4D and age (all, P >0.05). The area under the curve of right hand 2D:4D in male was 0.72 (95% CI 0.683-0.753, p<0.001), while it was 0.602 (95% CI 0.565-0.639, p<0.001) in left hand. CONCLUSIONS: The present study showed an association between high 2D:4D ratio and CAD in both hands in men. There were no significant differences in mean 2D:4D between women with CAD and controls.

[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.