Shen Hongbing, Solari Ana, Wang Xinru, Zhang Zhengdong, Xu Yaochu, Wang Liwei, Hu Xu, Guo Jiantao, Wei Qingyi
Department of Epidemiology and Statistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Oncol Rep. 2004 May;11(5):1115-20.
The p53 gene plays an important role in cell cycle control in response to DNA damage, which may increase the probability of mutations that lead to carcinogenesis. The p53 codon 72 Arg right curved arrow Pro polymorphism has been suggested to be associated with risk for different kind of cancers, but the data on gastric cancer (GC) is very limited. To evaluate the association between this polymorphism and risk of GC, we performed genotype analysis by using a polymerase chain reaction-based restriction fragment length polymorphism assay in a population-based case-control study of 324 GC patients and 317 cancer-free controls in a Chinese population. The controls were frequency-matched to the cases by age, sex and smoking status. The frequency of the p53 Arg allele was 57.4% in the cases and 54.9% in the controls, and the genotype frequencies of p53 Arg/Arg, Arg/Pro, and Pro/Pro were 29.6%, 55.6%, and 14.8%, respectively, in the cases, and 29.6%, 50.5%, and 19.9%, respectively, in the controls (p=0.207). Logistic regression analysis revealed that the p53 Arg allele (Arg/Pro and Arg/Arg genotype) was associated with a borderline significantly increased risk of gastric cancer (adjusted OR=1.44, 95% CI=0.95-2.18), particularly non-cardia gastric cancer (adjusted OR=1.67, 95% CI=1.00-2.77), compared with p53 homozygous Pro allele (Pro/Pro genotype), and the risk was significantly more evident among alcohol drinkers (adjusted OR=2.85, 95% CI=1.37-5.95). While the results suggest that the p53 codon 72 polymorphism may contribute to gastric cancer susceptibility, further larger studies are needed to substantiate our findings and to explore a possible interaction between p53 codon 72 polymorphism and alcohol in the etiology of gastric cancer.
p53基因在响应DNA损伤的细胞周期调控中发挥重要作用,这可能会增加导致癌变的突变概率。p53密码子72的精氨酸(Arg)向脯氨酸(Pro)的多态性已被认为与不同类型癌症的风险相关,但关于胃癌(GC)的数据非常有限。为了评估这种多态性与胃癌风险之间的关联,我们在中国人群中一项基于人群的病例对照研究中,对324例胃癌患者和317例无癌对照进行了基于聚合酶链反应的限制性片段长度多态性分析,以进行基因型分析。对照在年龄、性别和吸烟状况方面与病例进行了频率匹配。p53精氨酸等位基因的频率在病例组中为57.4%,在对照组中为54.9%;p53精氨酸/精氨酸(Arg/Arg)、精氨酸/脯氨酸(Arg/Pro)和脯氨酸/脯氨酸(Pro/Pro)的基因型频率在病例组中分别为29.6%、55.6%和14.8%,在对照组中分别为29.6%、50.5%和19.9%(p = 0.207)。逻辑回归分析显示,与p53纯合脯氨酸等位基因(Pro/Pro基因型)相比,p53精氨酸等位基因(Arg/Pro和Arg/Arg基因型)与胃癌风险显著增加相关(校正比值比[OR]=1.44,95%可信区间[CI]=0.95 - 2.18),特别是非贲门胃癌(校正OR = 1.67,95% CI = 1.00 - 2.77),并且在饮酒者中风险更为明显(校正OR = 2.85,95% CI = 1.37 - 5.95)。虽然结果表明p53密码子72多态性可能与胃癌易感性有关,但需要进一步的大规模研究来证实我们的发现,并探索p53密码子72多态性与酒精在胃癌病因学中可能存在的相互作用。