Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Genetic medicine in companion diagnostics of germline BRCA testing of Japanese pancreatic cancer patients


In 2021, Japan’s national health insurance made germline BRCA (g.BRCA) testing available to unresectable pancreatic cancer (PC) patients as a companion diagnostic (CD) of the PARP inhibitor. This study investigated the incidence of the g.BRCA variant (g.BRCAv.) and the status of the genetic medicine associated with its testing. A total of 110 PC patients underwent the testing, five of whom (4.5%) had a deleterious g.BRCA2v. (all truncations) but no g.BRCA1v. The turnaround time (TAT) to the doctors was 13 days, and to the patients, 17 days. A higher incidence of a BRCA-related family history and a shorter TAT were seen in the g.BRCAv. patients, but they were insignificant (p = 0.085 and p = 0.059, respectively). Genetic counseling was not performed for three g.BRCA2v. patients because two of them had no accessible relatives and one died of the cancer before the genetic report was completed. Two families underwent generic counseling and testing based on the patient’s genetic data. g.BRCAv. is recognized in a small fraction of PC cases, and the following genetic counseling is done more for the relatives than for the patients. TAT was constant and did not affect much on the genetic counseling, but the earlier testing is expected for patients with a deadly cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

Similar content being viewed by others


  1. Miki Y. [Cellular functions of BRCA genes - from basic science to therapeutics]. Gan Kagaku Ryoho. 2012;39:498–501.

    CAS  Google Scholar 

  2. Casolino R, Paiella S, Azzolina D, Beer PA, Corbo V, Lorenzoni G, et al. Homologous recombination deficiency in pancreatic cancer: a systematic review and prevalence meta-analysis. J Clin Oncol. 2021;39:2617–31.

    Article  CAS  Google Scholar 

  3. Frank TS, Deffenbaugh AM, Reid JE, Hulicket M, Ward BE, Lingenfelter B, et al. Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol. 2002;20:1480–90.

    Article  CAS  Google Scholar 

  4. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl J Med. 2009;361:123–34.

    Article  CAS  Google Scholar 

  5. Golan T, Hammel P, Reni M, Cutsem EV, Macarulla T, Hall MJ, et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N. Engl J Med. 2019;381:317–27.

    Article  CAS  Google Scholar 

  6. Hirasawa A, Masuda K, Akahane T, Tsuruta T, Banno K, Makita K, et al. Experience of risk-reducing salpingo-oophorectomy for a BRCA1 mutation carrier and establishment of a system performing a preventive surgery for hereditary breast and ovarian cancer syndrome in Japan: our challenges for the future. Jpn J Clin Oncol. 2013;43:515–9.

    Article  Google Scholar 

  7. Heemskerk-Gerritsen BA, Rookus MA, Aalfs CM. Ausems MGEM, Collee IM, Jansenet M, et al. Improved overall survival after contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer: a prospective analysis. Int J Cancer. 2015;136:668–77.

    CAS  Google Scholar 

  8. Japanese Organization of Hereditary Breast and Ovarian Cancer. Guidelines for Diagnosis and Treatment of Hereditary Breast and Ovarian Cancer 2021.

  9. Daly MB, Pal T, Berry MP, Buys S, Dickson P, Domchek SM, et al. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2021;19:77–102.

    Article  CAS  Google Scholar 

  10. Pujol P, Barberis M, Beer P, Friedman E, Piulats JM, Capluongo ED, et al. Clinical practice guidelines for BRCA1 and BRCA2 genetic testing. Eur J Cancer. 2021;146:30–47.

    Article  CAS  Google Scholar 

  11. Higashigawa S, Matsubayashi H, Kiyozumi Y, Kado N, Nishimura S, Oishi T, et al. Present status of germline findings in precision medicine for Japanese cancer patients: issues in the current system. Jpn J Clin Oncol. 2022;52:599–608.

    Article  Google Scholar 

  12. Minamoto A, Yamada T, Shimada S, Kinoshita I, Aoki Y, Oda K, et al. Current status and issues related to secondary findings in the first public insurance covered tumor genomic profiling in Japan: multi-site questionnaire survey. J Hum Genet. 2022;67:557–63.

    Article  Google Scholar 

  13. Matsubayashi H, Sasaki K, Ono S, Ishiwatari H, Ishikawa K, Satoh T, et al. Efficacy of endoscopic samplings during initial biliary drainage for cases of pancreatic head cancer: United diagnostic yields of multiple pathological samplings. Pancreatology. 2021;21:1548–54.

    Article  CAS  Google Scholar 

  14. Japan Pancreas Society. Classification of Pancreatic Carcinoma. Fourth English Edition. Tokyo: Kanehara & Co., Ltd., 2017.

  15. Pannala R, Basu A, Petersen GM, Chari ST. New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer. Lancet Oncol. 2009;10:88–95.

    Article  Google Scholar 

  16. Baretta Z, Mocellin S, Goldin E, Olopade OI, Huo D. Effect of BRCA germline mutations on breast cancer prognosis: A systematic review and meta-analysis. Med (Baltim). 2016;95:e4975.

    Article  CAS  Google Scholar 

  17. Nakamura Y, Taniguchi H, Ikeda M, Bando H, Kato K, Morizane C, et al. Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies. Nat Med. 2020;26:1859–64.

    Article  CAS  Google Scholar 

  18. Mizukami K, Iwasaki Y, Kawakami E, Hirata M, Kamatani Y, Matsuda K, et al. Genetic characterization of pancreatic cancer patients and prediction of carrier status of germline pathogenic variants in cancer-predisposing genes. EBioMedicine. 2020;60:103033.

    Article  Google Scholar 

  19. Sahin I, Saat H. A novel BRCA1 duplication and new insights on the spectrum and frequency of germline large genomic rearrangements in BRCA1/BRCA2. Mol Biol Rep. 2021;48:5057–62.

    Article  CAS  Google Scholar 

  20. Sluiter MD, van Rensburg EJ. Large genomic rearrangements of the BRCA1 and BRCA2 genes: review of the literature and report of a novel BRCA1 mutation. Breast Cancer Res Treat. 2011;125:325–49.

    Article  CAS  Google Scholar 

  21. Judkins T, Rosenthal E, Arnell C, Burbidge LA, Geary W, Barrus T, et al. Clinical significance of large rearrangements in BRCA1 and BRCA2. Cancer. 2012;118:5210–6.

    Article  CAS  Google Scholar 

  22. Kim SH, Hwang HK, Lee WJ, Kang CM. Biologic behavior of resected BRCA-mutated pancreatic cancer: Comparison with sporadic pancreatic cancer and other BRCA-related cancers. Pancreatology. 2021;21:544–9.

    Article  CAS  Google Scholar 

  23. Liu Y, Ide Y, Inuzuka M, Tazawa S, Kanada Y, Matsunaga Y, et al. BRCA1/BRCA2 mutations in Japanese women with ductal carcinoma in situ. Mol Genet Genom Med. 2019;7:e493.

    Article  Google Scholar 

  24. Yoshida R, Watanabe C, Yokoyama S, Inuzuka M, Yotsumoto J, Arai M, et al. Analysis of clinical characteristics of breast cancer patients with the Japanese founder mutation BRCA1 L63X. Oncotarget. 2019;10:3276–84.

    Article  Google Scholar 

  25. Sekine M, Enomoto T, Arai M, Yokoyama S, Nomura H, Nishino K, et al. Correlation between the risk of ovarian cancer and BRCA recurrent pathogenic variants in Japan. J Hum Genet. 2022;67:267–72.

    Article  CAS  Google Scholar 

  26. Cancer Statistics in Japan 2022.

  27. Arai M, Yokoyama S, Watanabe C, Yoshida R, Kita M, Okawa M, et al. Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan. J Hum Genet. 2018;63:447–57.

    Article  Google Scholar 

  28. Matsubayashi H, Takaori K, Morizane C, Maguchi H, Mizuma M, Takahashi H, et al. Familial pancreatic cancer: concept, management and issues. World J Gastroenterol. 2017;23:935–48.

    Article  Google Scholar 

Download references


We thank all of nurses and genetic coordinators in Shizuoka Cancer Center.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Hiroyuki Matsubayashi.

Ethics declarations

Competing interests

The authors declare no competing interests

Ethical standards

Institutional Review Board of Shizuoka Cancer Center ethically approved this study (Institutional code no.: J2022-61).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsubayashi, H., Todaka, A., Kawakami, T. et al. Genetic medicine in companion diagnostics of germline BRCA testing of Japanese pancreatic cancer patients. J Hum Genet 68, 81–86 (2023).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links