DNA Repair Genes as Drug Candidates for Early Breast Cancer Onset in Latin America: A Systematic Review

Int J Mol Sci. 2021 Dec 2;22(23):13030. doi: 10.3390/ijms222313030.

Abstract

The prevalence of breast cancer in young women (YWBC) has increased alarmingly. Significant efforts are being made to elucidate the biological mechanisms concerning the development, prognosis, and pathological response in early-onset breast cancer (BC) patients. Dysfunctional DNA repair proteins are implied in BC predisposition, progression, and therapy response, underscoring the need for further analyses on DNA repair genes. Public databases of large patient datasets such as METABRIC, TCGA, COSMIC, and cancer cell lines allow the identification of variants in DNA repair genes and possible precision drug candidates. This study aimed at identifying variants and drug candidates that may benefit Latin American (LA) YWBC. We analyzed pathogenic variants in 90 genes involved in DNA repair in public BC datasets from METABRIC, TCGA, COSMIC, CCLE, and COSMIC Cell Lines Project. Results showed that reported DNA repair germline variants in the LA dataset are underrepresented in large databases, in contrast to other populations. Additionally, only six gene repair variants in women under 50 years old from the study population were reported in BC cell lines. Therefore, there is a need for new approaches to study DNA repair variants reported in young women from LA.

Keywords: DNA repair genes; breast cancer datasets; breast cancer in young women; cell lines; therapy.

Publication types

  • Systematic Review

MeSH terms

  • BRCA1 Protein / genetics
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • DNA Repair / genetics*
  • Female
  • Humans
  • Latin America
  • Mutation
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53