中国人群中VEGF基因启动子区-460T/C与-634G/C单倍型与结肠癌的易感性研究

目的探讨血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)基因启动子区-460T/C与-634G/C多态性位点单倍型在中国汉族人群中与结肠癌发生的易感性关联。方法外周血样本DNA提取后,采用PCR-限制性片段长度多态性技术(PCR-restriction fragment length polymorphism,PCR-RFLP)检测182例结肠癌患者与216例健康对照者VEGF基因启动子区-460T/C、-634G/C位点多态性;并利用PHASE 1.0软件构建其单倍型,以非条件Logistic回归校正混杂因素,进行单倍型与结肠癌易感风险的统计学分析。结果 VEGF基因-460T/C与-634G/C位点多态性在中国人群中均存在,且基因频率分布符合Hardy-Weinberg平衡定律;-460T/C多态性位点在检测的结肠癌患者与正常人群中,等位基因频率差异有统计学意义(P=0.002),而-634G/C位点等位基因频率在两组间比较差异无统计学意义(P=0.103);在单倍型统计分析中,VEGF基因多态性位点-460C与-634C组成的C-C单倍型频率在两组人群中差异无统计学意义(P<0.001,OR=4.28)(95%CI:2.77～13.41)。结论VEGF基因启动子区-460T/C与-634G/C多态性位点组成的单倍型C-C与结肠癌的发生有易感风险关联。

Susceptibility study of the haplotype from VEGF gene promoter -460T/C and -634G/C polymorphisms and the risk of colorectal cancer in Chinese subjects

Objective This study was performed to elucidate whether the vascular endothelial growth factor(VEGF) gene haplotypes were associated with the colorectal cancer risk in the Han ethnic group of China.Methods Association was analyzed in a hospital-based case-control study involving 182 colorectal cancer cases and 216 cancer-free controls. DNA was obtained from blood samples and the polymorphisms of -460T/C and -634G/C were genotyped by the method of PCR-RFLP. The software PHASE1.0 was performed to construct the haplotypes of every individual. Unconditional logistic regression model was used to analyze the statistical association of haplotypes in two groups adjusted by gender, age, smoking, drinking, and the family history of cancer. Results Both the -460T/C and -634G/C loci in the VEGF gene promoter were carried out in the Chinese individuals. The distributions of the VEGF genotypes among cases and controls were in Hardy-Weinberg equilibrium. There was significant difference in allele frequency of -460T/C polymorphism between the colorectal cancer patients and normal subjects(P=0.002) while, there was no significant difference in -634G/C polymorphism(P=0.103). The haplotypes analysis showed that the result exhibited a significantly higher level of haplotype C-C in colorectal cancer patients compared to control subjects(P<0.001; OR=4.28, 95%CI: 2.77-13.41). Conclusion Based on these findings, it seemed that the haplotype C-C constructed by the VEGF gene promoter -460T/C and -634G/C polymorphisms may contribute to the susceptibility of colorectal cancer in the Chinese population.