TP53基因多态与中国人群结直肠癌遗传易感性的相关性

TP53 gene polymorphisms and colorectal cancer risk in Chinese population

目的探讨 TP53基因 C-8343G、C-1863T 及第72密码子(CGC/CCC,其编码氨基酸分别为精氨酸 R 和脯氨酸 P,R72P)单核苷酸多态(SNP)与中国人群结直肠癌(CRC)遗传易感性的关系。方法采用 TaqMan 和聚合酶链反应-限制性片段长度多态方法,检测345例 CRC 患者与670名对照 SNP 的基因型分布及差异。结果 C-8343G和 C-1863T 基因型分布在 CRC、对照两组人群间差异无统计学意义(P>0.05)。R72P 在两组人群中的基因型及等位基因分布差异有统计学意义(P<0.01)。与 RR 纯合子相比,RP 杂合子和 PP 纯合子的 CRC 风险分别增加至1.60倍(95%CI=1.17～2.18,P<0.01)和2.37倍(95%CI=1.61～3.47,P<0.01)。饮酒可进一步增加 R72P 多态的 CRC 风险效应:以 RR 饮酒者为参照,RP 和 PP 饮酒者的 CRC 风险分别为3.01倍(95%CI=1.48～6.12)和4.71倍(95%CI=1.90～11.68)。结论 TP53基因 C-8343G 和 C-1863T 多态与 CRC 风险无关;R72P多态增加中国人群,特别是饮酒人群的 CRC 发病风险。

Objective To investigate the association between the single nucleotide polymorphisms （SNPs） in TP53 gene and susceptibility to colorectal cancer （CRC） in Chinese population. Methods Peripheral blood samples were collected and white cell genomic DNA was extracted from 345 CRC patients, 198 males and 1447 females, aged （58.7 ± 13.5）, and 670 sex, age, smoking and drinking situationsmatched controls in Ningbo city, Zhejiang province The genotypes of the SNPs of C-8343G, C-1863T, and R72P in TP53 gene were determined by either TaqMan assays or PCR-based restriction fragment length polymorphism method. Unconditional logistic regression was used to calculate the odds ratio （OR） for CRC after adjustment of the covariates, such as sex, age, cigarette smoking, alcohol drinking, body mass index and first-degree family history of CRC, and 95% confidence intervals （CI） so as to evaluate relative risk . Results There were not significant differences in the above mentioned covariates between these 2 groups. No significant association of C-8343G or C-1863T polymorphism with CRC risk was observed （ both P 〉 0. 05）. The CRC risk of the 72P genotype was 50. 3% , 1.53 times that of the 72R genotype （39.6%） （95% CI = 1.27-1.85, P 〈 0. 01 ）. The CRC risk of the RP heterozygotes was 1.60 times that of the RP homozygote （95% CI = 1.17-2.18, P 〈 0.01 ）, and the CRC risk of the PP homozygotes was 2.37 times that of the RP heterozygotes （95% CI = 1.61-3.47, P 〈 0.01 ）. A dose-response relationship was shown （P 〈0.01 ）. Stratified analysis indicated that the 72P allele conferred a more pronounced increase in CRC risk among the alcohol consumers： the CRC risk was 3.01 times for the RP heterozygotes （95% CI = 1.48- 6.12）, and4.71 times for the PP homozygotes （95% CI=1.90-11.68）. Conclusion TP53 C-8343G and C-1863T polymorphisms are not associated with CRC risk. R72P polymorphism contributes to the etiology of CRC in the Chinese population, particularly among the alcohol consumers.