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. 2024 May 3;4(3):309-314.
doi: 10.21873/cdp.10325. eCollection 2024 May-Jun.

High Frequency of BRCA2 c.5576_5579del Carriers in Kakogawa, Japan

Haruna Nakamura  1   2 , Sachiko Mizumoto  2 , Hirokazu Tanino  3 , Yui Niwa  4   5 , Mitsutoshi Ogino  1 , Yoko Sakoda  1 , Kazuhiko Tsuchiya  1 , Seishi Kono  6 , Muneharu Konishi  7 , Sayaka Ueno  8 , Tomonari Kunihisa  2
Affiliations

High Frequency of BRCA2 c.5576_5579del Carriers in Kakogawa, Japan

Haruna Nakamura et al. Cancer Diagn Progn. .

Abstract

Background/aim: Certain germline pathogenic variants (PVs), known as founder mutations, have been frequently observed in specific regions and ethnic groups. In Japan, several pathogenic variants of BRCA1/2 have been identified as founder mutations, with their distribution varying across different regions. This retrospective study aimed to further investigate the detailed distribution and correlation between genotype and clinical features among breast cancer patients.

Patients and methods: This study was conducted at Kobe University Hospital and three collaborating institutions. It included breast cancer patients who underwent BRCA1/2 genetic testing between July 1, 2018, and March 31, 2021, and were found to have germline PVs. Clinical characteristics and breast cancer subtypes were compared between carriers of BRCA2 c.5576_5579del and those with other PVs. Additionally, the detection rate of BRCA2 c.5576_5579del was compared with that observed in a previous report.

Results: A total of 38 breast cancer patients were included; PVs in BRCA1 and BRCA2 were detected in 12 and 26 patients, respectively, 12 of whom were BRCA2 c.5576_5579del carriers. BRCA2 c.5576_5579del carriers were more likely to develop triple negative breast cancers among all BRCA2 PV carriers. BRCA2 c.5576_5579del accounted for 30.8% of the PVs detected, with a particularly high frequency of 72.7% at Kakogawa Central City Hospital.

Conclusion: BRCA2 c.5576_5579del was detected with a particularly high frequency in Hyogo Prefecture, especially in Kakogawa city. In the future, a survey of the distribution of the BRCA2 c.5576_5579del carriers may provide more clarity regarding their localization.

Keywords: BRCA2 c5576_5579del; Breast cancer; Japan; founder mutation; hereditary breast and ovarian cancer.

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Conflict of interest statement

Sachiko Mizumoto, Hirokazu Tanino and Tomonari Kunihisa received a research grant from Ono Pharmaceutical Co. Ltd. Tomonari Kunihisa is a lecturer in an endowed chair founded by Hyogo Prefecture. The other Authors declare no conflicts of interest in relation to this study.

Figures

Figure 1
Figure 1. The carrier frequency among the four participating hospitals. The BRCA1/2 carrier frequency was compared in patients among four hospitals. The frequency of PVs in the observed patients was also compared with that in Japanese patients reported by Yoshimura et al. (4). A pie chart was used to compare the proportion of PVs at each hospital. BRCA2 c.5576_5579del accounted for 30.8% of the PVs detected in this study and was detected with a particularly high frequency at Kakogawa Central City Hospital, accounting for 72.7% of the PVs observed there.
See this image and copyright information in PMC

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