期刊
HUMAN MUTATION
卷 30, 期 4, 页码 661-668出版社
WILEY
DOI: 10.1002/humu.20931
关键词
TP53; CDKN1A; CDKN2A; genetic polymorphisms; haplotype analysis; colorectal cancer susceptibility; CRC
资金
- Czech Republic [GACR 310/07/1430, AVOZ 50390703, AVOZ 50390512, GAUK 96908/8/2008]
- BMBF
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: A(1)>A(2), rs1042522:G>C, rs12947788: C>T, and rs17884306:G>A), CDKN1A (rs1801270: C>A and 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 ill the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), 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 A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (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 P < 0.000 1) and rectal cancers (P = 0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population. Hum Mutat 30, 661-668, 2009. (C) 2009 Wiley-Liss, Inc.
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