肿瘤抑制基因TP53的年龄相关功能：对癌症风险和进展的影响
Age-related function of tumor suppressor gene TP53:contribution to cancer risk and progression.
作者信息
Cherdyntseva N V, Gervas P A, Litvyakov N V, Stakcheeva M N, Ponomaryeva A A, Dobrodeev A Yu, Denisov E V, Belyavskaya V A, Choinzonov E L
机构信息
Department of Immunology, Cancer Research Institute of RAMS, Kooperativny str 5, Tomsk 634050, Russia.
出版信息
Exp Oncol. 2010 Sep;32(3):205-8.
AIM
To examine the influence of combined genotypes of TP53 (exon 4, intron 3, intron 6) and XRCC1 (codon 10) on lung cancer age of onset.
METHODS
TP53 polymorphisms in codon 72 of exon 4 (Arg72Pro), in intron 3 (16 bp duplication), in intron 6 (G/A transition) and XRCC1 polymorphism in codon 10 (Arg399Gln) were analyzed in blood cells of 177 lung cancer patients and 196 healthy donors with Restriction Fragment Lenth Polymorphism PCR.
RESULTS
We showed that combination of TP53 variant genotypes and XRCC1 variant genotype is associated with the increased lung cancer risk in younger, but not elderly, smokers. In contrast, wild allele combination increases lung cancer risk for individuals over the age of 60.
CONCLUSION
Our data confirm antagonistic pleiotropy hypothesis indicating that p53 protects the organism against cancer early in life, but promoting aging phenotype, including late life cancer in older persons.
目的
研究TP53（外显子4、内含子3、内含子6）和XRCC1（密码子10）的联合基因型对肺癌发病年龄的影响。
方法
采用限制性片段长度多态性聚合酶链反应，分析177例肺癌患者和196例健康供者血细胞中TP53第4外显子密码子72（Arg72Pro）、内含子3（16bp重复）、内含子6（G/A转换）的多态性以及XRCC1密码子10（Arg399Gln）的多态性。
结果
我们发现，TP53变异基因型与XRCC1变异基因型的组合与年轻吸烟者而非老年吸烟者患肺癌风险增加有关。相反，野生等位基因组合会增加60岁以上个体患肺癌的风险。
结论
我们的数据证实了拮抗多效性假说，表明p53在生命早期保护机体免受癌症侵害，但会促进衰老表型，包括老年人晚年患癌。
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