Duncan, A.; Nousome, D.; Ricks, R.; Kuo, H.-C.; Ravindranath, L.; Dobi, A.; Cullen, J.; Srivastava, S.; Chesnut, G.T.; Petrovics, G.; Kohaar, I. Association of TP53 Single Nucleotide Polymorphisms with Prostate Cancer in a Racially Diverse Cohort of Men. Biomedicines2023, 11, 1404.
Duncan, A.; Nousome, D.; Ricks, R.; Kuo, H.-C.; Ravindranath, L.; Dobi, A.; Cullen, J.; Srivastava, S.; Chesnut, G.T.; Petrovics, G.; Kohaar, I. Association of TP53 Single Nucleotide Polymorphisms with Prostate Cancer in a Racially Diverse Cohort of Men. Biomedicines 2023, 11, 1404.
Duncan, A.; Nousome, D.; Ricks, R.; Kuo, H.-C.; Ravindranath, L.; Dobi, A.; Cullen, J.; Srivastava, S.; Chesnut, G.T.; Petrovics, G.; Kohaar, I. Association of TP53 Single Nucleotide Polymorphisms with Prostate Cancer in a Racially Diverse Cohort of Men. Biomedicines2023, 11, 1404.
Duncan, A.; Nousome, D.; Ricks, R.; Kuo, H.-C.; Ravindranath, L.; Dobi, A.; Cullen, J.; Srivastava, S.; Chesnut, G.T.; Petrovics, G.; Kohaar, I. Association of TP53 Single Nucleotide Polymorphisms with Prostate Cancer in a Racially Diverse Cohort of Men. Biomedicines 2023, 11, 1404.
Abstract
Growing evidence indicates the involvement of a genetic component for CaP susceptibility and clinical severity. Somatic mutations of TP53 have been associated with 50% of diverse human cancers. Studies have also reported the role of germ line mutations and single nucleotide poly-morphisms (SNPs) of TP53 as possible risk factors for cancer development. In this single De-partment of Defense institutional retrospective study, we identified common SNPs in the TP53 gene in AA and CA men and performed association analyses for functional TP53 SNPs with clinico-pathological features of CaP. The CPDR Oncoarray database on blood derived genomic DNA from 321 men treated by radical prostatectomy at WRNMMC were used to examine clini-co-pathological associations with TP53 SNPs. The SNP genotyping analysis on the final cohort of 308 patients (212 AA; 95 CA) identified 74 SNPs in the TP53 gene region with a minor allele fre-quency (MAF) of at least 1%. Two SNPs were non-synonymous in the exonic region of TP53: rs1800371 (Pro47Ser) and rs1042522 (Arg72Pro). The Pro47Ser variant, had a minor allele frequency of 0.01 in AA, however, was not detected in CA. Arg72Pro was the most common SNP with a minor allele frequency of 0.50 (0.41 in AA; 0.68 in CA). Additionally, Arg72Pro was associated with time to biochemical recurrence (BCR) after statistical adjustment for patient age at diagnosis, self-reported race, and Gleason score (p= 0.046; HR = 1.52).
The present study demonstrated ancestral differences in allele frequencies of TP53 Arg72Pro and Pro47Ser SNPs in AA and CA CaP, providing a valuable framework for the interrogating CaP disparity among AA and CA men.
Keywords
prostate cancer; SNP; TP53; Pro47Ser; Arg72Pro; African American
Subject
Biology and Life Sciences, Life Sciences
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
