TP53 Arg72Pro, mortality after cancer, and all-cause mortality in 105,200 individuals.
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.
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.
Jakob B
JB
Kodal
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.
Signe
S
Vedel-Krogh
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.
Camilla J
CJ
Kobylecki
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.|The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Børge G
BG
Nordestgaard
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, DK-2730, Herlev, Denmark. stig.egil.bojesen@regionh.dk.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. stig.egil.bojesen@regionh.dk.|The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. stig.egil.bojesen@regionh.dk.
Stig E
SE
Bojesen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics / Q000401:mortality; D003718:Denmark / Q000453:epidemiology; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality*; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics*; D020125:Mutation, Missense; D018570:Risk Assessment; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
D050505:Mutant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53