Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic

Abstract

The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A1 > A2 rs1042522:G>C, rs12947788: C>T, and rs17884306:G>A), CDKNIA (rs1801270: C>Aand rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C> G, and rs3088440: C> T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P< 0.0001). The two most common haplotypes, A1GCG and A2CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A1GCG), the haplotype A2CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A1CCG (OR, 0.60; 95% CI, 0.45-0.79), A2GCG (OR, 0.53; 95% CI, 0.35-0.81), A1GTG (OR, 0.31; 95% CI, 0.15-0.64), and A1GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global < 0.0001) and rectal cancers (P = 0.006). No association with the disease was observed with haplotypes of the CDKNIA and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population. © 2009 Wiley-Liss, Inc.