In search of TP53 mutational hot spots for Li-Fraumeni syndrome in Asian populations

Trop Med Int Health. 2021 Nov;26(11):1401-1410. doi: 10.1111/tmi.13673. Epub 2021 Oct 4.

Abstract

Objective: Germline mutations of the TP53 tumour suppressor gene are the only known cause of the hereditary autosomal disorder called Li-Fraumeni syndrome (LFS). However, little information is available about TP53 pathogenic variants in Asian LFS patients, making it difficult to provide precise genetic counselling with regard to long-term cancer risk. We conducted a systematic review to gather relevant case-control studies exploring the association between TP53 polymorphisms and the incidence of cancer belonging to the LFS spectrum in Asian populations.

Method: Systematic review and meta-analysis. The odds ratio was used as a summary effect measure to quantify the strength of the association between TP53 polymorphisms and cancer risk by means of random-effects meta-analysis.

Results: In total, 16 studies were included in this systematic review, with 13 studies (involving 10,645 cases and 28,288 controls) that enabled meta-analysis. The majority of the studies focused on a single-nucleotide variation at codon 72 in exon 4 (c.215C>G, p.Arg72Pro, rs1042522). Therefore, we tested either dominant, co-dominant, recessive, or heterozygous models and found that the p.Arg72Pro was not significantly associated with increased cancer risk in any of the models.

Conclusion: We found the number of studies on cancers belonging to the LFS spectrum in Asia is very small. Thus, at the present time a meta-analysis approach is somewhat useful to identify germline TP53 mutations as potential markers of hereditary cancer associated with LFS in Asian populations.

Keywords: TP53; Asian populations; Li-Fraumeni syndrome; genetic variants; hereditary cancer; markers.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Asia / epidemiology
  • Asian People
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation
  • Humans
  • Li-Fraumeni Syndrome / epidemiology
  • Li-Fraumeni Syndrome / genetics*
  • Polymorphism, Single Nucleotide
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Tumor Suppressor Protein p53