Germline BRCA mutations in Asian patients with pancreatic adenocarcinoma: a prospective study evaluating risk category for genetic testing
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 o...
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Published in | Investigational new drugs Vol. 36; no. 1; pp. 163 - 169 |
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Main Authors | , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.02.2018
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0167-6997 1573-0646 |
DOI: | 10.1007/s10637-017-0497-1 |