Cancer Res Treat.  2019 Jul;51(3):941-950. 10.4143/crt.2018.312.

Clinical and Genetic Characteristics of BRCA1/2 Mutation in Korean Ovarian Cancer Patients: A Multicenter Study and Literature Review

• Kwon BS
• Byun JM
• Lee HJ
• Jeong DH
• Lee TH
• Shin KH
• Suh DS
• Kim KH

• KMID: 2454286
• DOI: http://doi.org/10.4143/crt.2018.312

Abstract

PURPOSE
We investigated the clinical relevance and spectrum of BRCA1/2 mutations in Korean ovarian cancer (KoOC) patients.
MATERIALS AND METHODS
Two hundred seventy-nine KoOC patients were enrolled from three university hospitals between 2012 and 2017. Their peripheral blood samples were obtained for BRCA1/2 mutation analysis by direct sequencing. Clinicopathological characteristics were retrospectively reviewed, and spectrum analyses of BRCA1/2 mutation were assessed by systematic literature review.
RESULTS
Frequency of BRCA1/2 mutations was 16.5% in KoOC patients. BRCA1/2 mutations were significantly associated with family history of breast/ovarian cancer (p<0.001), serous histology (p=0.044), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV, p=0.018) but not with early age-of-onset (age < 50, p=0.729). Literature review of BRCA1/2 mutations in KoOC patients found 111 (55 distinct) mutations with high proportion of Korean-specific mutations (24/55, 43.6%). Comparing the spectrum of BRCA1/2 mutation between KoOC and Korean breast cancer (KoBC) patients, the ratio of BRCA1-to-BRCA2 mutations was different, with BRCA1 (78.4%) being predominant in KoOC and BRCA2 in KoBC (59.2%). The most common mutation also differed between the two (c.3627insA of BRCA1 in KoOC and c.7480C>T of BRCA2 in KoBC).
CONCLUSION
The clinical relevance of BRCA1/2 mutations in KoOC patients was confirmed but that of early age-of-onset was not. Possible inconsistency in the ratio of BRCA1-to-BRCA2 mutations and the most common mutation between KoOC and KoBC may probably suggest presence of mutation sequence-associated penetrance tendency in hereditary Korean breast and ovarian cancer. These data may provide insights for optimal genetic counseling and prophylactic treatment for at-risk relatives of KoOC patients.

Keyword

BRCA1 genes; BRCA2 genes; Germ-line mutation; Koreans; Ovarian neoplasms

MeSH Terms

Asian Continental Ancestry Group
Breast
Breast Neoplasms
Genes, BRCA1
Genes, BRCA2
Genetic Counseling
Germ-Line Mutation
Gynecology
Hospitals, University
Humans
Obstetrics
Ovarian Neoplasms*
Penetrance
Retrospective Studies

Figure

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  Fig. 1. Prevalence of BRCA1/2 mutations in unselected 279 Korean ovarian cancer patients. The overall prevalence (A) and prevalence according to family history of breast/ovarian cancer (FHBOC) (B).

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  Fig. 2. Spectrum analysis of 111 (55 distinct) BRCA1/2 mutations detected in Korean ovarian cancer (KoOC) patients. The ratio of BRCA1 to BRCA2 mutations and most frequent mutation in KoOC patients (A), and the corresponding values in in Korean breast cancer patients as analyzed in the Korean Hereditary Breast Cancer (KOHBRA) study (B). The proportions of Korean population-specific mutation to non-Korean population-specific mutation (C) and recurrent mutation to non-recurrent mutation (D).

Reference

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