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Mismatch Repair01:20

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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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DNA Distortion and Damage
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One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
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gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair
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Germline DNA Repair Genes Pathogenic Variants Among Mexican Patients With Prostate Cancer.

Yanin Chávarri-Guerra1, María T Bourlon1, José L Rodríguez-Olivares2

  • 1Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Clinical Genitourinary Cancer
|June 28, 2023
PubMed
Summary

Genetic testing for prostate cancer in Mexican men revealed a low prevalence of pathogenic variants (PVs) in DNA repair genes. Younger men were more likely to carry these variants, suggesting unique risk factors in this population.

Keywords:
Genetic cancer risk assessmentGenotypeGermline mutationHispanicProstatic neoplasm

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Area of Science:

  • Genetics
  • Oncology
  • Population Health

Background:

  • Early identification of germline mutation carriers is crucial for prostate cancer management and familial risk assessment.
  • Population minorities often face limited access to genetic testing, hindering comprehensive cancer risk evaluation.
  • Understanding the frequency of pathogenic variants (PVs) in DNA repair genes is essential for specific ethnic groups.

Purpose of the Study:

  • To determine the prevalence of pathogenic variants (PVs) in DNA repair genes among Mexican men diagnosed with prostate cancer.
  • To assess the utility of Genomic Cancer Risk Assessment and genetic testing in a minority population.
  • To identify potential differences in genetic risk factors for prostate cancer in Mexican men.

Main Methods:

  • A cohort of 199 Mexican men with prostate cancer, meeting genetic testing criteria, was enrolled.
  • Descriptive statistics (frequency, proportions, median, range) were used to analyze patient data.
  • Chi-squared and t-tests were employed for statistical comparisons between groups.

Main Results:

  • A total of 199 men were analyzed, with a median age at diagnosis of 66 years.
  • Four participants (2%) carried a pathogenic germline variant in ATM, CHEK2, BRIP1, or MUTYH genes.
  • Younger men at diagnosis were significantly more likely to carry a pathogenic variant (P = .01).

Conclusions:

  • The study found a low prevalence of known prostate cancer-associated pathogenic variants, including BRCA, in Mexican men.
  • This low prevalence suggests that genetic and/or epidemiologic risk factors for prostate cancer may not be well-characterized in this population.
  • Further research is needed to elucidate the specific genetic landscape of prostate cancer in Mexican men.