Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, DK-2730, Herlev, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Sci Rep. 2017 Mar 23;7(1):336. doi: 10.1038/s41598-017-00427-x.
Rs1042522 (Arg72Pro) is a functional polymorphism of TP53. Pro72 has been associated with lower all-cause mortality and lower mortality after cancer. We hypothesized that TP53 Pro72 is associated with lower mortality after cancer, lower all-cause mortality, and with increased cancer incidence in the general population in a contemporary cohort. We genotyped 105,200 individuals aged 20-100 years from the Copenhagen General Population Study, recruited in 2003-2013, and followed them in Danish health registries. During follow-up 5,531 individuals died and 5,849 developed cancer. Hazard ratios for mortality after cancer were 1.03 (95% confidence interval:0.93-1.15) for Arg/Pro and 0.96 (95% CI:0.79-1.18) for Pro/Pro versus Arg/Arg. Hazard ratios for all-cause mortality were 0.99 (95% CI:0.93-1.04) for Arg/Pro and 1.09 (95% CI:0.98-1.21) for Pro/Pro versus Arg/Arg. Risk of cancer specific mortality, cardiovascular mortality, and respiratory mortality were not associated with Arg72Pro genotype overall; however, in exploratory subgroup analyses, genotype-associated risks of malignant melanoma and diabetes were altered. Considering multiple comparisons the latter findings may represent play of chance. The TP53 Arg72Pro genotype was not associated with mortality after cancer, all-cause mortality, or cancer incidence in the general population in a contemporary cohort. Our main conclusion is therefore a lack of reproducing an effect of TP53 Arg72Pro genotype on mortality.
rs1042522（Arg72Pro）是 TP53 的一个功能多态性。Pro72 与全因死亡率降低和癌症后死亡率降低有关。我们假设 TP53 Pro72 与癌症后死亡率降低、全因死亡率降低以及一般人群中癌症发病率增加有关。我们对 2003-2013 年招募的哥本哈根普通人群研究中的 105200 名年龄在 20-100 岁的个体进行了基因分型，并在丹麦健康登记处对他们进行了随访。在随访期间，有 5531 人死亡，5849 人发生癌症。与 Arg/Pro 相比，Arg/Arg 个体中癌症后死亡率的危险比为 1.03（95%可信区间：0.93-1.15），Pro/Pro 为 0.96（95%可信区间：0.79-1.18）。与 Arg/Arg 相比，Arg/Pro 和 Pro/Pro 个体的全因死亡率危险比分别为 0.99（95%可信区间：0.93-1.04）和 1.09（95%可信区间：0.98-1.21）。总体而言，Arg72Pro 基因型与癌症特异性死亡率、心血管死亡率和呼吸死亡率无关；然而，在探索性亚组分析中，恶性黑色素瘤和糖尿病的基因型相关风险发生了改变。考虑到多次比较，后一种发现可能代表偶然发生。在当代队列的一般人群中，TP53 Arg72Pro 基因型与癌症后死亡率、全因死亡率或癌症发病率无关。因此，我们的主要结论是缺乏复制 TP53 Arg72Pro 基因型对死亡率的影响。
