Germline BRCA mutations in Asian patients with pancreatic adenocarcinoma: a prospective study evaluating risk category for genetic testing
| Autor: | Kyoung-Jin Park, Myung-Hwan Kim, Tae Jun Song, Dong Wan Seo, Jae Hoon Lee, Sang Hyun Shin, Do Hyun Park, Dae Wook Hwang, Sung Koo Lee, Song Cheol Kim, Heung-Moon Chang, Woochang Lee, Kyu-Pyo Kim, Sang Soo Lee, Tae Won Kim, Kyoungmin Lee, Changhoon Yoo, Ki Byung Song, Baek-Yeol Ryoo, Jae-Lyun Lee |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Oncology medicine.medical_specialty endocrine system diseases Population Breast Neoplasms Adenocarcinoma Germline 03 medical and health sciences 0302 clinical medicine Asian People Risk Factors Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Pharmacology (medical) Medical history Genetic Testing 030212 general & internal medicine Family history Medical History Taking skin and connective tissue diseases education Prospective cohort study Germ-Line Mutation Aged Genetic testing BRCA2 Protein Ovarian Neoplasms Pharmacology education.field_of_study medicine.diagnostic_test BRCA1 Protein business.industry Middle Aged medicine.disease Progression-Free Survival Pancreatic Neoplasms 030220 oncology & carcinogenesis Female Ovarian cancer business |
| Zdroj: | Investigational New Drugs. 36:163-169 |
| ISSN: | 1573-0646 0167-6997 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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