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Background <p>The absence of population-specific genetic variant frequency data in Indonesia complicates the interpretation of germline genetic variants of DNA repair genes critical for cancer predisposition.</p> Objective <p>to estimate baseline frequency of pathogenic/likely pathogenic germline variants (P/LP) and variant of unknown significance (VUS), we conducted an exploratory genetic screening in a convenience sample of 255 hospital staff without personal history of cancer, i.e. healthy subjects.</p> Methods <p>A cross-sectional study was conducted at Dharmais Cancer Centre, Indonesia. 156 (61%) and 99 subjects (39%) reported absence and presence of family history (FH) of cancer, respectively. Peripheral blood DNA was sequenced using the Illumina 113-gene TruSight hereditary panel, and variants were classified according to the American College of Medical Genetics (ACMG) guidelines.</p> Results <p>Twelve out of 255 subjects or 4.71% (95% CI: 2.45–8.09%) carried P/LP variants of <i>MUTYH</i>,<i> XPA</i>,<i> XPC</i>,<i> FANCA</i>,<i> FANCC</i>,<i> CHEK2</i> and Homologous DNA Repair (<i>BRCA1</i>, <i>BRCA2</i>, <i>BRIP1</i>, and <i>RAD51D</i>) genes. Five out of 99 with FH (5.1%) and seven out 156 subjects (4.48%) without FH had P/LP variants. There were 4 subjects (1.56%) harboring P/LP variants of <i>BRCA1</i> (1.17%) and <i>BRCA2</i> (0.39%) genes. <i>BRCA1</i> and <i>FANCA</i> P/LP variants were found exclusively in 5 subjects with FH. One subject with FH carried dual P/LP variants of <i>BRCA1</i> and <i>CHEK2</i> genes. 21.6% subjects with and without family history had VUS in HRR genes.</p> Conclusions <p>The P/LP germline variants were detected in healthy subjects with and without family history. Furthermore, we detected several VUS that were potentially to be reclassified as benign since their prevalence in healthy subjects was more common than the rate of the disease.</p>

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Prevalence of germline 113 cancer genes in healthy Indonesian hospital staff

  • 期刊论文

  • 发表日期：

    2025年12月27日

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  • Mega Hayati,
  • Fahreza Saputra,
  • Hubertus Hosti Hayuanta,
  • Lyana Setiawan,
  • Ahmad Rusdan H. Utomo

摘要

Background

The absence of population-specific genetic variant frequency data in Indonesia complicates the interpretation of germline genetic variants of DNA repair genes critical for cancer predisposition.

Objective

to estimate baseline frequency of pathogenic/likely pathogenic germline variants (P/LP) and variant of unknown significance (VUS), we conducted an exploratory genetic screening in a convenience sample of 255 hospital staff without personal history of cancer, i.e. healthy subjects.

Methods

A cross-sectional study was conducted at Dharmais Cancer Centre, Indonesia. 156 (61%) and 99 subjects (39%) reported absence and presence of family history (FH) of cancer, respectively. Peripheral blood DNA was sequenced using the Illumina 113-gene TruSight hereditary panel, and variants were classified according to the American College of Medical Genetics (ACMG) guidelines.

Results

Twelve out of 255 subjects or 4.71% (95% CI: 2.45–8.09%) carried P/LP variants of MUTYH, XPA, XPC, FANCA, FANCC, CHEK2 and Homologous DNA Repair (BRCA1, BRCA2, BRIP1, and RAD51D) genes. Five out of 99 with FH (5.1%) and seven out 156 subjects (4.48%) without FH had P/LP variants. There were 4 subjects (1.56%) harboring P/LP variants of BRCA1 (1.17%) and BRCA2 (0.39%) genes. BRCA1 and FANCA P/LP variants were found exclusively in 5 subjects with FH. One subject with FH carried dual P/LP variants of BRCA1 and CHEK2 genes. 21.6% subjects with and without family history had VUS in HRR genes.

Conclusions

The P/LP germline variants were detected in healthy subjects with and without family history. Furthermore, we detected several VUS that were potentially to be reclassified as benign since their prevalence in healthy subjects was more common than the rate of the disease.