ArticleJournal of the National Cancer Institute2025
TP53 missense allele predisposing to high risk of breast cancer but not pediatric cancers.
Article in Journal of the National Cancer Institute, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Variation at the R181 Residue of p53 Confers Loss of p53 DNA Binding Cooperativity with the Retention of Mitochondria-Associated Apoptosis.Molecular cancer research : MCR · 2026Article
- Low-penetrance TP53 variants are mainly hypomorphic: an underestimated issue with high clinical significance.NPJ genomic medicine · 2026Article
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Authors and funding
18 authors.
Funding
Abstract
Pathogenic TP53 germline variants cause young-onset breast cancer and other cancers of the Li-Fraumeni syndrome (LFS) spectrum, but the clinical consequences of partial-loss-of function TP53 variants are incompletely understood. In the consecutive cohort of Palestinian breast cancer patients of the Middle East Breast Cancer Study (MEBCS), breast cancer risk among TP53 p.R181C heterozygotes was 50% by age 50 years and 81% by age 80 years. In contrast, prevalence of pediatric cancers in the MEBCS was similar among first-degree relatives of TP53 p.R181C carriers (3/519 = 0.0058) and first-degree relatives of MEBCS patients with no pathogenic germline variant in any known breast cancer gene (7/1082 = 0.0065; odds ratio [OR] = 0.90, 95% confidence interval [CI] [0.23 to 3.49], Fisher P = .90 [2-tailed]). This result suggests that in families harboring this TP53 allele, genetic testing in children is unwarranted, and screening children for LFS tumors is unnecessary. More generally, some TP53 missense alleles can predispose to very high risk of breast cancer without pleiotropic effects.
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