Association of TP53 gene polymorphisms with genetic susceptibility to liver metastases of colorectal cancer / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>