TP53 Arg72Pro, mortality after cancer, and all-cause mortality in 105,200 individuals

Abstract 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 inciden...

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Autores principales:	Jakob B. Kodal, Signe Vedel-Krogh, Camilla J. Kobylecki, Børge G. Nordestgaard, Stig E. Bojesen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/86379509186247929350a4e06c88b971
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spelling	oai:doaj.org-article:86379509186247929350a4e06c88b9712021-12-02T11:52:56ZTP53 Arg72Pro, mortality after cancer, and all-cause mortality in 105,200 individuals10.1038/s41598-017-00427-x2045-2322https://doaj.org/article/86379509186247929350a4e06c88b9712017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00427-xhttps://doaj.org/toc/2045-2322Abstract 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.Jakob B. KodalSigne Vedel-KroghCamilla J. KobyleckiBørge G. NordestgaardStig E. BojesenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jakob B. Kodal Signe Vedel-Krogh Camilla J. Kobylecki Børge G. Nordestgaard Stig E. Bojesen TP53 Arg72Pro, mortality after cancer, and all-cause mortality in 105,200 individuals
description	Abstract 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.
format	article
author	Jakob B. Kodal Signe Vedel-Krogh Camilla J. Kobylecki Børge G. Nordestgaard Stig E. Bojesen
author_facet	Jakob B. Kodal Signe Vedel-Krogh Camilla J. Kobylecki Børge G. Nordestgaard Stig E. Bojesen
author_sort	Jakob B. Kodal
title	TP53 Arg72Pro, mortality after cancer, and all-cause mortality in 105,200 individuals
title_short	TP53 Arg72Pro, mortality after cancer, and all-cause mortality in 105,200 individuals
title_full	TP53 Arg72Pro, mortality after cancer, and all-cause mortality in 105,200 individuals
title_fullStr	TP53 Arg72Pro, mortality after cancer, and all-cause mortality in 105,200 individuals
title_full_unstemmed	TP53 Arg72Pro, mortality after cancer, and all-cause mortality in 105,200 individuals
title_sort	tp53 arg72pro, mortality after cancer, and all-cause mortality in 105,200 individuals
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/86379509186247929350a4e06c88b971
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TP53 Arg72Pro, mortality after cancer, and all-cause mortality in 105,200 individuals

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