Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of Czech Republic, Videnska 1083, 14200 Prague, Czech Republic.
Carcinogenesis. 2010 Apr;31(4):666-70. doi: 10.1093/carcin/bgq032. Epub 2010 Jan 28.
Pancreatic carcinoma is the fourth leading cause of cancer-related deaths in the Czech Republic, with only a minimum of patients surviving 5 years. The aetiology and molecular pathogenesis are still weakly understood. TP53 has a fundamental role in cell cycle and apoptosis and is frequently mutated in solid tumours, including pancreatic cancer. Based on the assumption that genetic variation may affect susceptibility to cancer development, the role of TP53 polymorphisms in modulating the risk of pancreatic cancer may be of major importance. We investigated four selected polymorphisms in TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T and rs17884306:G>A) in association with pancreatic cancer risk in a case-control study, including 240 cases and controls (for a total of 1827 individuals) from the Czech Republic. Carriers of the variant C allele of rs1042522 polymorphism were at an increased risk of pancreatic cancer [odds ratio (OR) 1.73; 95% confidence interval (CI) 1.26-2.39; P = 0.001]. Haplotype analysis showed that in comparison with the most common haplotype (A(1)GCG), the A(2)CCG haplotype was associated with an increased risk (OR 1.39; 95% CI 1.02-1.88; P = 0.034) and the A(1)CCG with a reduced risk (OR 0.30; 95% CI 0.12-0.76; P = 0.011) for this cancer. These results reflect previous findings of a recent association study, where haplotypes constructed on the same TP53 variants were associated with colorectal cancer risk [Polakova et al. (2009) Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. Hum. Mutat., 30, 661-668.]. Genetic variation in TP53 may contribute, alone or in concert with other risk factors, to modify the inherited susceptibility to pancreatic cancer, as well as to other gastrointestinal cancers.
在捷克共和国，胰腺癌是癌症相关死亡的第四大主要原因，只有极少数患者能存活 5 年以上。其病因和分子发病机制仍知之甚少。TP53 在细胞周期和细胞凋亡中起着重要作用，在包括胰腺癌在内的实体肿瘤中经常发生突变。基于遗传变异可能影响癌症发展易感性的假设，TP53 多态性在调节胰腺癌风险中的作用可能非常重要。我们在一项病例对照研究中研究了 TP53 中的四个选定多态性（rs17878362:A(1)>A(2)、rs1042522:G>C、rs12947788:C>T 和 rs17884306:G>A）与胰腺癌风险的关系，包括来自捷克共和国的 240 例病例和对照（总共 1827 人）。携带 rs1042522 多态性的 C 等位基因变异的个体患胰腺癌的风险增加[比值比（OR）1.73；95%置信区间（CI）1.26-2.39；P = 0.001]。单体型分析表明，与最常见的单体型（A(1)GCG）相比，A(2)CCG 单体型与增加的风险相关（OR 1.39；95%CI 1.02-1.88；P = 0.034），A(1)CCG 与降低的风险相关（OR 0.30；95%CI 0.12-0.76；P = 0.011）。这些结果反映了最近一项关联研究的结果，其中构建在相同 TP53 变体上的单体型与结直肠癌风险相关[Polakova 等人（2009 年）捷克共和国散发性结直肠癌中细胞周期基因的基因型和单体型分析。人类突变，30，661-668]。TP53 中的遗传变异可能单独或与其他危险因素一起，改变对胰腺癌以及其他胃肠道癌症的遗传易感性。
