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Germline BRCA mutations in Asian patients with pancreatic adenocarcinoma: a prospective study evaluating risk category for genetic testing

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Summary

Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy. Analyses for germline BRCA mutations were performed if patients had one or more first-degree or second-degree relatives with breast or ovarian cancers or had a personal medical history of these diseases. DNA was extracted from whole blood, and all coding exons and their flanking intron regions of BRCA1 and BRCA2 were sequenced. Results A total of 175 patients were screened for personal and family history and 10 (5.7%) met the inclusion criteria for genetic sequencing. Pathogenic germline BRCA2 mutation [c.7480C>T (p.Arg2494*)] was identified in one male patient, resulting in a frequency of 10% for the risk-stratified patients and 0.6% for the unselected PDAC population. Two patients had germline BRCA2 variants of uncertain significance [c.1744A>C (p.Thr582Pro) and c.68-7T>A]. Conclusion Personal or family history of breast or ovarian cancers is a feasible, cost-effective risk categorization for screening germline BRCA mutations in Asian PDAC patients as 10% of this population had the pathogenic mutation herein. Future validation from a large, prospective cohort is needed.

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Author notes

  1. Changhoon Yoo and Baek-Yeol Ryoo equally contributed to this work.

Authors and Affiliations

  1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro, 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea

    Kyoungmin Lee, Changhoon Yoo, Kyu-pyo Kim, Heung-Moon Chang, Tae Won Kim, Jae-Lyun Lee & Baek-Yeol Ryoo

  2. Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Kyoung-Jin Park & Woochang Lee

  3. Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dong Wan Seo, Sung Koo Lee & Myung-Hwan Kim

  4. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Sang Hyun Shin, Dae Wook Hwang, Ki Byung Song, Jae Hoon Lee & Song Cheol Kim

Authors
  1. Kyoungmin Lee
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  2. Changhoon Yoo
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  20. Baek-Yeol Ryoo
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Corresponding authors

Correspondence to Changhoon Yoo or Baek-Yeol Ryoo.

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Funding

This study was supported by a grant (2015–0753) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.

Conflict of interest

The authors indicate no potential conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

This study was approved by the Institutional Review Board of the Asan Medical Center and informed consent was obtained from all individual participants included in the study.

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Lee, K., Yoo, C., Kim, Kp. et al. Germline BRCA mutations in Asian patients with pancreatic adenocarcinoma: a prospective study evaluating risk category for genetic testing. Invest New Drugs 36, 163–169 (2018). https://doi.org/10.1007/s10637-017-0497-1

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