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A Population-Based Analysis of BRCA1/2 Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study

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Abstract
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Although it has been suggested that cancer risk and genetic variation vary by population, there is still a lack of research on non-European populations. In this study, we applied Korean patients as a model to find out the way to conduct BRCA1/2-related clinical studies in non-European populations who do not have as much clinical data as Europeans. The BRCA1/2 variants were classified following the 2015 ACMG standards/guidelines and using a multifactorial probability-based approach. To estimate the additional sample numbers needed to resolve BRCA1/2 unclassified status, we applied a simulation analysis considering population-specific clinical characteristics. In addition, we estimated the risks of breast or ovarian cancer for BRCA1/2 carriers by mutation regions. Data from this study reveal that BRCA1/2 variants in the non-European population are highly specific; therefore, population-specific study is essential for clinical application of treatment or prevention for breast or ovarian cancer.

In this study, we performed a comprehensive analysis of BRCA1/2 variants and associated cancer risk in Korean patients considering two aspects: variants of uncertain significance (VUS) and pathogenic or likely pathogenic variants (PLPVs) in BRCA1 and BRCA2. This study included 5433 Korean participants who were tested for BRCA1/2 genes. The BRCA1/2 variants were classified following the standards/guidelines for interpretation of genetic variants and using a multifactorial probability-based approach. In Korea, 15.8% of participants had BRCA1 or BRCA2 PLPVs. To estimate the additional sample numbers needed to resolve unclassified status, we applied a simulation analysis. The simulation study for VUS showed that the smaller the number of samples, the more the posterior probability was affected by the prior probability; in addition, more samples for BRCA2 VUS than those of BRCA1 VUS were required to resolve the unclassified status, and the presence of clinical information associated with their VUS was an important factor. The cumulative lifetime breast cancer risk was 59.1% (95% CI: 44.1-73.6%) for BRCA1 and 58.3% (95% CI: 43.2-73.0%) for BRCA2 carriers. The cumulative lifetime ovarian cancer risk was estimated to be 36.9% (95% CI: 23.4-53.9%) for BRCA1 and 14.9% (95% CI: 7.4-28.5%) for BRCA2 carriers.
Author(s)
박경선이우창성문우공선영이경아하정숙조은해한성희박인호김종원
Issued Date
2021
Type
Article
Keyword
BRCA1BRCA2breast cancerovarian cancervariants of uncertain significancecumulative risk
DOI
10.3390/cancers13092192
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8598
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_422dcb320dd549b0baaf6c934bf02834&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,A%20Population-Based%20Analysis%20of%20BRCA1%2F2%20Genes%20and%20Associated%20Breast%20and%20Ovarian%20Cancer%20Risk%20in%20Korean%20Patients:%20A%20Multicenter%20Cohort%20Study&offset=0&pcAvailability=true
Publisher
CANCERS
Location
스위스
Language
영어
ISSN
2072-6694
Citation Volume
13
Citation Number
9
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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