Characterization of TP53 polymorphisms in Romanian colorectal cancer patients

摘要

The tumor suppressor TP53 gene is one of the commonest mutated genes in colorectal cancer. Beside somatic mutations, the gene harbors numerous genetic variations that may alter the protein functionality, affecting cancer risk and clinical outcome. Among genetic variations, single nucleotide polymorphisms were investigated in relation to cancer risk, including colorectal cancer susceptibility. The studies revealed that the distribution of polymorphic alleles and their functional relevance varied in a population-dependent manner. In the present work we analyzed the distribution of eleven TP53 genetic variants in a lot of 63 colorectal cancer patients. The polymorphisms with minor allele frequency between 12%-21% and the resulting haplotypes were examined for association with clinicopathological features of colorectal tumors, TP53 somatic mutations and allelic instability at TP53 locus. The polymorphisms rs1625895, rs1042522, rs1642785 and rs17878362 located in intron 6, exon 4, intron 2 and intron 3, respectively were in strong linkage. The most common haplotypes GGGA1 and ACCA2 were present in 86.4% of the cases. Individual polymorphisms distribution and the two major haplotypes were statistic significantly associated with gender and age of disease onset, the expression of minor alleles and ACCA2 haplotype being prevalent in men and associated with an earlier age of the disease onset.