TP53基因多态与结直肠癌肝转移遗传易感性的相关性

目的 探讨TP53基因C-8343G、C-1863T及第72密码子(R72P)单核苷酸多态性与结直肠癌(colorectal cancer,CRC)肝转移风险的关系.方法 采用TaqMan和聚合酶链反应-限制性片段长度多态性方法,检测121例伴肝转移CRC与性别、年龄匹配的280例不伴肝转移CRC的各单核苷酸多态性的基因型分布及差异.结果 C-8343G和C-1863T基因型分布在伴和不伴肝转移的两组CRC人群间差异均无统计学意义.R72P增加CRC肝转移的发生风险:与PP基因型相比,RP基因型、RR基因型和R等位基因携带者(RP或RR基因型)的肝转移风险分别增加至2.21倍(95%CI:1.13～4.33)、2.26倍(95%CI:1.03～4.94)和2.22倍(95%CI:1.16～4.26).CRC组织中P53表达状态的分层分析结果显示:对于P53表达阳性者,72R携带者的肝转移风险与PP基因型相比进一步增加至3.28倍(95%CI:1.21～8.88);而对于P53表达阴性者,PP基因型与72R携带者的肝转移风险差异无统计学意义(比值比为1.37,95%CI:0.52～3.62).结论 TP53增加CRC,特别是P53表达阳性CRC的肝转移风险,可作为CRC肝转移高危人群的筛选指标;C-8343G和C-1863T可能均与CRC肝转移风险无关.

Association of TP53 gene polymorphisms with genetic susceptibility to liver metastases of colorectal cancer

OBJECTIVE: To investigate the possible association between the single nucleotide polymorphisms (SNPs) (C-8343G, C-1863T and R72P) in TP53 gene and susceptibility to liver metastases of colorectal cancer (CRC) in a Chinese population. METHODS: The genotypes of each SNP in TP53 gene were determined by either TaqMan assays or PCR-based restriction fragment length polymorphism (RFLP) method in 121 colorectal cancer patients with liver metastases and sex-, age-matched 280 cases with nonmetastatic CRC as a control. Immunohistochemical staining for P53 was performed on paraffin-embedded sections. Odds ratios (ORs) for colorectal liver metastases and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. RESULTS: No significant association of C-8343G or C-1863T with colorectal liver metastases risk was observed. However, the R allele of the TP53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases (P= 0.037). When compared with PP homozygotes, the ORs of metastases for RP heterozygotes was 2.21 (95% CI: 1.13-4.33), for RR homozygotes was 2.26 (95% CI: 1.03-4.94), and for carriers of the 72R allele (RP or RR genotype) was 2.22 (95% CI: 1.16-4.26). Stratified analysis indicated that carrying the 72R allele had a more pronounced increase in colorectal liver metastases risk among patients with positive P53 expression tumors (OR= 3.28, 95% CI: 1.21-8.88), whereas no significantly increased metastases risk was found in patients with negative P53 expression tumors (OR= 1.37, 95% CI: 0.52-3.62). CONCLUSION: The R allele of the TP53 R72P polymorphism may contribute to the etiology of liver metastases in CRC patients, particularly among those with positive P53 expression tumors. Both TP53 C-8343G and C-1863T may be not associated with colorectal liver metastases risk.