Abstract IA20: A coding region variant in the TP53 tumor-suppressor gene may underlie cancer disparities in African Americans

Abstract

In addition to being frequently mutated in sporadic cancer, the p53 tumor suppressor also contains several coding region variants that alter function and can contribute to increased cancer risk. We previously published that the Pro47Ser variant of p53 exists in approximately 1-2% of individuals of African descent, and that this variation prevents a key phosphorylation event on p53, and reduces the ability of this protein to induce cell death (1). We recently published a mouse model for this variant, and show that this mouse develops a striking incidence of sporadic cancer, predominantly hepatocellular cancer but also including cancers of the pancreas, stomach, and intestine. In a cohort of African American women with breast cancer, we found evidence for an association of Pro47Ser with pre-menopausal cancer incidence (HR 1.7, p 1. Li X, Dumont P, Della Pietra A, Shetler C, Murphy ME. The codon 47 polymorphism in p53 is functionally significant. J Biol Chem 2005;280(25):24245-51. PubMed PMID: 15851479. 2. Murphy ME, Liu S, Yao S, et al. A functionally significant SNP in TP53 and breast cancer risk in African-American women. NPJ Breast Cancer 2017;3:5. PubMed Central PMCID: PMC5445618. 3. Jennis M, Kung CP, Basu S, et al. An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model. Genes Dev 2016;30(8):918-30. PubMed Central PMCID: PMC4840298. 4. Basu S, Barnoud T, Kung CP, Reiss M, Murphy ME. The African-specific S47 polymorphism of p53 alters chemosensitivity. Cell Cycle 2016;15(19):2557-60. PubMed Central PMCID: PMC5053554. Citation Format: Maureen E. Murphy. A coding region variant in the TP53 tumor-suppressor gene may underlie cancer disparities in African Americans [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA20.