p53基因多态及单体型分布与乳腺癌危险性的关联研究

Association of p53 polymorphisms and its haplotypes with susceptibility of breast cancer

目的:探讨p53第72密码子Arg/Pro多态、第3内含子16bp副本和第6内含子G/A多态与乳腺癌的关系。方法:采用以自然人群为基础的病例对照设计,对84例乳腺癌患者和以1∶2频数匹配原则获得的168例对照进行研究,p53基因3种多态的基因分型采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析。单体型分布采用EHlinkage software 1.2分析软件进行估计和比较。结果:乳腺癌患者组和对照组吸烟状况的分布差异有统计学意义,病例组曾经或现在吸烟的个体比例为7.1%,明显高于对照组的1.2%(χ2=6.455,P=0.018),年龄、饮酒状况及一二级亲属家族恶性肿瘤史等基本特征因素分布差异均无统计学意义(P>0.05)。p53的这3种多态基因型在两组间的分布均无统计学意义上的差异(P>0.05)。经上述因素校正后发现,p53的3种基因多态与乳腺癌发病亦没有统计学意义上的关联(P>0.05)。应用EHlinkage software 1.2单体型分析软件显示,上述3种基因多态在对照组内存在连锁不平衡现象,Arg-A-G和Pro-A-G是最常见的2类单体型。单体型组间分布亦不具有显著性差异(P>0.05)。结论:p53基因的上述3种多态与乳腺癌发病风险可能不存在关联,各基因多态存在连锁不平衡现象,Arg-A-G和Pro-A-G是最常见的2类单体型。

Objective. To investigate the association of p53 polymorphisms with susceptibility to breast cancer in Chinese Han population. Methods. In this population-based case-control study,84 cases with breast cancers and 168 controls,matched to the cases in terms of gender, habitation and age （5 years）,were genotyped for codon 72,intron 3,and intron 6 polymorphisms in p53 gene by polymerase chain reaction-restriction-fragment length polymorphism （PCR -RFLP ） methods. The haplotype distribution was estimated and compared by EH linkage software 1.2. Results： The distributions of age,alcohol drinking,family history of cancer in first and second relatives were not significantly different between cases and controls. There was significant association between cigarette smoking and breast cancer （Х^2 = 6. 455,P = 0. 018） ,the percentage of ever or current smokers was significantly higher in cases （7. 1%） than that in controls （1.2 %）. The distributions of allelotype and genotype of codon72,intron 3,and intron 6 were also not significantly different between cases and controls （P 〉 0. 05）. No significant association was found between the risk of breast cancer and p53 polymorphisms. The genetic linkage disequilibrium existed in these three polymorphic sites in controls,and the Arg-A-G and Pro-A-G were the most common haplotypes both in cases and controls. There was no significant association of p53 haplotype with risk of breast cancer. Conclusion： p53 codon72,intron 3,and intron 6 polymorphisms may not be associated with the susceptibility of breast cancer. The Arg- A-G and Pro-A-G haplotypes are the most common haplotypes in Chinese Han population.