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Correlation between the risk of ovarian cancer and BRCA recurrent pathogenic variants in Japan

Journal of Human Genetics volume 67, pages 267–272 (2022)Cite this article

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Abstract

We previously reported that L63X and Q934X are BRCA1 common founder variants in Japan. So far, there have been no reports of a correlation between such BRCA common variants and the risk of BRCA-related cancers. In this analysis, we investigated the correlation between the risk of ovarian cancer (OC) and BRCA recurrent pathogenic variants. We examined the database of the Japanese organization of hereditary breast and ovarian cancer. The database contained 3517 probands who underwent BRCA genetic testing. Among them, 11.1% (392/3517) had germline BRCA1 pathogenic variant, and 8.3% (293/3517) had BRCA2 pathogenic variant. We calculated the OC prevalence, breast cancer (BC) prevalence, and the ratio of OC to BC within second-degree relatives. The ratio of OC to BC in Q934X family members was significantly higher than that in the overall BRCA1 family members (0.80 vs.0.52: p = 0.038), and the ratio in STOP799 was 0.42, which was relatively lower than the overall BRCA1 value. Both Q934X and STOP799 are located in the ovarian cancer cluster region (OCCR), however there seems to be a difference in the risk of OC. R2318X family members had a significant higher ratio of OC to BC at 0.32 than the overall BRCA2 value of 0.13 (p = 0.012). R2318X is known to be located in the OCCR. This is the first report to investigate the correlation between BRCA recurrent variants and the risk of OC in Japan. The family members of probands with Q934X or R2318X have a higher risk of OC than that with other BRCA variants.

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Fig. 1: Results of BRCA1/2 genetic testing of 3517 probands in the JOHBOC registry.

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Acknowledgements

JOHBOC Registration Committee [Committee]: Tadashi Nomizu (Hoshi General Hospital), Akihiro Sakurai (Sapporo Medical University), Megumi Okawa (St. Luke’s International Hospital), Junko Yotsumoto (International University of Health and Welfare), Hiraku Kumamaru (The University of Tokyo), [Secretariat of JOHBOC] Miyuki Shimoda. Participating Facilities of Nationwide registration projects: Aichi Cancer Center Hospital, Asahikawa Medical University, Cancer Institute Hospital, Chiba University, Ehime University, Fujita Medical University, Fukui University, Fukushima Medical University, Gifu University, Gunma Prefectural Cancer Center, Hiroshima Prefectural Hospital, Hiroshima University, Hokkaido Cancer Center, Hokkaido University, Hoshi General Hospital, Ibaraki Prefectural Hospital, Ishikawa Prefectural Central Hospital, Iwate Medical University, JA Hiroshima General Hospital, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Japanese Red Cross Ishinomaki Hospital, Japanese Red Cross Medical Center, Japanese Red Cross Nagoya Daiichi Hospital, Japanese Red Cross Saitama Hospital, Japanese Red Cross Yamaguchi Hospital, JCHO Saitama Medical Center, Jisenkai Aizawa Hospital, Juntendo University, Kanagawa Cancer Center, Kanazawa University, Kansai Medical University, Kansai Rosai Hospital, Kawasaki Medical School, Keio University, Kitakyushu Municipal Medical Center, Kitano Hospital, Kitazato University, Kochi Medical Center, Kochi University, Kokura Medical Center, Konan Kosei Hospital, Kyoto University, Nagasaki University, Nagoya City University, Nagoya University, Nara Medical University, National Hospital Organization Kyoto Medical Center, National Hospital Organization Osaka National Hospital, Nihonkai General Hospital, Niigata Cancer Center Hospital, Niigata University, Nippon Medical School, Nippon Medical School Musashi Kosugi Hospital, Okayama University, Osaka University, Sagara Hospital Breast Center, Saitama Cancer Center, Saitama Medical Center, Saitama Medical University International Medical Center, Saku Medical Center, Sapporo Medical University, Seirei Hamamatsu General Hospital, Shiga University of Medical Science, Shikoku Cancer Center, Shinshu University, Shiroyama Hospital, Shizuoka Cancer Center, Shizuoka General Hospital, Shonan Memorial Hospital, Showa Medical University Hospital, St. Lukes Hospital, St. Marianna University School of Medicine, Tawara IVF Clinic, The Jikei University, Tokuyama Central Hospital., Tokyo Medical Center, Tokyo Metropolitan Komagome Hospital, Tosei General Hospital, Tottori University, University of Tsukuba, Yamagata Prefectural Central Hospital, Yamaguchi University, Yamanashi Prefectural Central Hospital, and Yokohama City University.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Masayuki Sekine, Takayuki Enomoto & Koji Nishino

  2. Clinical Genetics, Juntendo University, Graduate School of Medicine, Tokyo, Japan

    Masami Arai

  3. Division of Breast Surgical Oncology, Department of Surgery, Showa University School of Medicine, Tokyo, Japan

    Shiro Yokoyama & Seigo Nakamura

  4. Department of Obstetrics and Gynecology, School of Medicine, Fujita Health University, Aichi, Japan

    Hiroyuki Nomura

  5. Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan

    Takeshi Ikeuchi

  6. Center for Medical Genetics, Niigata University Medical and Dental Hospital, Niigata, Japan

    Yoko Kuriyama

  7. Department of Surgery, Hoshi General Hospital, Fukushima, Japan

    Tadashi Nomizu

  8. Department of Medical Genetics, Sapporo Medical University, Hokkaido, Japan

    Akihiro Sakurai

  9. St. Luke’s International Hospital, Tokyo, Japan

    Megumi Okawa

  10. Department of Genetic Counseling, Graduate School of Health and Welfare Sciences, International University of Health and Welfare, Tokyo, Japan

    Junko Yotsumoto

  11. Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Hiraku Kumamaru

  12. Secretariat of JOHBOC, Tokyo, Japan

    Miyuki Shimoda

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  1. Masayuki Sekine
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Consortia

The Registration Committee of the Japanese Organization of Hereditary Breast and Ovarian Cancer

  • Tadashi Nomizu
  • , Akihiro Sakurai
  • , Megumi Okawa
  • , Junko Yotsumoto
  • , Hiraku Kumamaru
  •  & Miyuki Shimoda

Corresponding author

Correspondence to Masayuki Sekine.

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Competing interests

M.S. received lecture fees from AstraZeneca. T.E. received lecture fees from AstraZeneca and Chugai Pharmaceutical. S.N. received lecture fees from AstraZeneca and KONICA MINOLTA. Other authors declare no competing interests.

Ethics approval

The ethics review board of the Japanese HBOC Consortium approved the establishment of the database to investigate Japanese HBOC patients’ characteristics. This registration has been begun after obtaining further approval from the institutional review board of each medical institution where BRCA genetic testing and genetic counseling were available.

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Sekine, M., Enomoto, T., Arai, M. et al. Correlation between the risk of ovarian cancer and BRCA recurrent pathogenic variants in Japan. J Hum Genet 67, 267–272 (2022). https://doi.org/10.1038/s10038-021-01002-z

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