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http://purl.uniprot.org/citations/20520810http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20520810http://www.w3.org/2000/01/rdf-schema#comment"

Background

Previous studies have shown that MDM2 SNP309 and p53 codon 72 have modifier effects on germline P53 mutations, but those studies relied on case-only studies with small sample sizes. The impact of MDM4 polymorphism on tumor onset in germline mutation carriers has not previously been studied.

Methodology/principal findings

We analyzed 213 p53 germline mutation carriers including 168(78.9%) affected with cancer and 174 who had genotypic data. We analyzed time to first cancer using Kaplan-Meier and Cox proportional hazards methods, comparing risks according to polymorphism genotypes. For MDM2 SNP309, a significant difference of 9.0 years in the average age of cancer diagnosis was observed between GG/GT and TT carriers (18.6 versus 27.6 years, P = 0.0087). The hazards ratio was 1.58 (P = 0.03) comparing risks among individuals with GG/GT to risk among TT, but this effect was only significant in females (HR = 1.60, P = 0.02). Compared to other genotypes, P53 codon 72 PP homozygotes had a 2.24 times (P = 0.03) higher rate for time to develop cancer. We observed a multiplicative joint effect of MDM2 and p53 codon72 polymorphism on risk. The MDM4 polymorphism had no significant effects.

Conclusions/significance

Our results suggest that the MDM2 SNP309 G allele is associated with cancer risk in p53 germline mutation carriers and accelerates time to cancer onset with a pronounced effect in females. A multiplicative joint effect exists between the MDM2 SNP309 G allele and the p53 codon 72 G allele in the risk of cancer development. Our results further define cancer risk in carriers of germline p53 mutations."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0010813"xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/author"Chen W."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/author"Han Y."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/author"Zhang B."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/author"Bachinski L.L."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/author"Amos C.I."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/author"Post S.M."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/author"Fang S."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/author"Krahe R."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/author"Strong L.C."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/author"Lozano G."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/author"Wilson C.D."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/pages"e10813"xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/title"Effects of MDM2, MDM4 and TP53 codon 72 polymorphisms on cancer risk in a cohort study of carriers of TP53 germline mutations."xsd:string
http://purl.uniprot.org/citations/20520810http://purl.uniprot.org/core/volume"5"xsd:string
http://purl.uniprot.org/citations/20520810http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20520810
http://purl.uniprot.org/citations/20520810http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20520810
http://purl.uniprot.org/uniprot/#_A0A087WTR9-mappedCitation-20520810http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20520810
http://purl.uniprot.org/uniprot/#_A0A087WUE3-mappedCitation-20520810http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20520810
http://purl.uniprot.org/uniprot/#_A0A0M4B4Y9-mappedCitation-20520810http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20520810
http://purl.uniprot.org/uniprot/#_A0A087WXZ1-mappedCitation-20520810http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20520810
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