Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population.
Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population.
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DOI：
10.1084/jem.20062476
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发表时间：
2007-06-11
期刊：
影响因子：
--
通讯作者：
Nordestgaard BG
中科院分区：
文献类型：
--
作者：
Ørsted DD;Bojesen SE;Tybjaerg-Hansen A;Nordestgaard BG
P53是一种重要的肿瘤抑制因子，通常通过细胞凋亡来阻止肿瘤的发展。基因组中P53蛋白的Arg72Pro替代对细胞通过凋亡而死亡有重要影响，这可能是有益的。因此，我们测试了假设，即这种多态会影响寿命、癌症诊断后的存活率以及普通人群中的癌症风险。我们调查了来自丹麦普通人群的9219名年龄在20-95岁之间的参与者，并进行了100%的随访。与Arg/Arg纯合子相比，P53Arg/Pro杂合子患者的12年总生存率提高了3%(P=0.003)，Pro/Pro纯合子患者的12年生存率提高了6%(P=0.002)，而Pro/Pro纯合子患者的中位生存期增加了3年。我们还证明，与Arg/Arg纯合子相比，Pro/Pro纯合子在癌症发展后，甚至在其他危及生命的疾病发展之后，存活率增加。Arg72Pro替代与癌症风险的降低无关。总而言之，在这个来自普通人群的大队列中，我们证明了众所周知的肿瘤抑制蛋白P53蛋白的功能性单核苷酸多态可以延长寿命，但不会降低癌症风险。寿命的延长可能是因为被诊断为癌症或其他危及生命的疾病后存活率增加。
p53 is an important tumor suppressor, normally preventing cancer development via apoptosis. A genomic Arg72Pro substitution in the p53 protein has important influence on cell death via apoptosis, which could be beneficial. We therefore tested the hypotheses that this polymorphism influences longevity, survival after a cancer diagnosis, and risk of cancer in the general population. We examined a cohort of 9,219 participants ages 20–95 from the Danish general population with 100% follow-up. The overall 12-yr survival was increased in p53 Arg/Pro heterozygotes with 3% (P = 0.003) and in Pro/Pro homozygotes with 6% (P = 0.002) versus Arg/Arg homozygotes, corresponding to an increase in median survival of 3 yr for Pro/Pro versus Arg/Arg homozygotes. We also demonstrated an increased survival after the development of cancer, or even after the development of other life-threatening diseases, for Pro/Pro versus Arg/Arg homozygotes. The Arg72Pro substitution did not associate with decreased risk of cancer. In conclusion, in this large cohort from the general population, we show that a well-known functional single nucleotide polymorphism in the tumor suppressor p53 protein leads to increased longevity, but not to decreased risk of cancer. The increased longevity may be due to increased survival after a diagnosis of cancer or other life-threatening diseases.
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