Intronic TP53 Polymorphisms Are Associated with Increased [DELTA]133TP53 Transcript, Immune Infiltration and Cancer Risk

• Published in: Cancers Vol. 12; no. 9; p. 1
• Main Authors: Eiholzer, Ramona A, Mehta, Sunali, Kazantseva, Marina, Drummond, Catherine J, McKinney, Cushla, Young, Katie, Slater, David, Morten, Brianna C, Avery-Kiejda, Kelly A, Lasham, Annette, Fleming, Nicholas, Morrin, Helen R, Reader, Karen, Royds, Janice A, Landmann, Michael, Petrich, Simone, Reddel, Roger, Huschtscha, Lily, Taha, Ahmad, Hung, Noelyn A, Slatter, Tania L, Braithwaite, Antony W
• Format: Journal Article
• Language: English
• Published: MDPI AG 01-09-2020
• Subjects: Cancer; Genetic aspects; Genetic polymorphisms; Health aspects; Risk factors; Australia
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12092472

We investigated the influence of genetic variants, called single nucleotide polymorphisms (SNP) in the TP53 tumour suppressor gene, on cancer risk, clinical features and TP53 isoform levels. These SNPs were significantly over-represented in cohorts of mixed cancers versus controls, suggesting they confer increased cancer risk. Heterozygosity at rs1042522(GC) and either of the two SNPs rs9895829(TC) and rs2909430(AG) confer up to a 5-fold greater risk of developing cancer. The SNP combinations were associated with high A133TP53 and TP53/S messenger RNA levels, elevated infiltrating immune cells and shorter patient survival for glioblastoma and prostate cancer. The data suggest that A133p53|3 protein levels are increased by the SNPs resulting in increased inflammation which contributes to more aggressive cancers.