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Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history
- Source :
- Genetics in medicine : official journal of the American College of Medical Genetics
- Publication Year :
- 2016
-
Abstract
- Background Panel-based genetic testing has identified increasing numbers of patients with pancreatic ductal adenocarcinoma (PDAC) who carry germline mutations. However, small sample sizes or number of genes evaluated limit prevalence estimates of these mutations. We estimated prevalence of mutations in PDAC patients with positive family history. Methods We sequenced 25 cancer susceptibility genes in lymphocyte DNA from 302 PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreatic Research Registry. Kindreds containing at least two first-degree relatives with PDAC met criteria for Familial Pancreatic Cancer (FPC), while the remaining were familial, but not FPC. Results Thirty-six patients (12%) carried at least one deleterious mutation in one of 11 genes. Of FPC patients, 25/185 (14%) were carriers, while 11/117 (9%) non-FPC patients with family history were carriers. Deleterious mutations (n) identified in PDAC patients were BRCA2 (11), ATM (8), CDKN2A (4), CHEK2 (4), MUTYH/MYH (3 heterozygotes, not biallelic), BRCA1 (2), and 1 each in BARD1, MSH2, NBN, PALB2, and PMS2. Novel mutations were found in ATM, BARD1, and PMS2. Conclusions Multiple susceptibility gene testing in PDAC patients with family history of pancreatic cancer is warranted regardless of FPC status, and will inform genetic risk counseling for families.
- Subjects :
- 0301 basic medicine
Oncology
Adult
Male
medicine.medical_specialty
endocrine system diseases
Genotype
PALB2
pancreatic ductal adenocarcinoma (PDAC)
Article
03 medical and health sciences
0302 clinical medicine
Germline mutation
MUTYH
CDKN2A
Internal medicine
Pancreatic cancer
Prevalence
Medicine
Humans
Genetic Predisposition to Disease
Genetic Testing
Registries
Family history
CHEK2
Genetics (clinical)
Alleles
Germ-Line Mutation
Aged
Aged, 80 and over
business.industry
Carcinoma
Cancer
High-Throughput Nucleotide Sequencing
Middle Aged
medicine.disease
digestive system diseases
United States
3. Good health
Pancreatic Neoplasms
030104 developmental biology
030220 oncology & carcinogenesis
Female
variants of uncertain significance (VUS)
business
Familial pancreatic cancer (FPC)
pathogenic variant (PV)
Subjects
Details
- ISSN :
- 15300366
- Volume :
- 20
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Genetics in medicine : official journal of the American College of Medical Genetics
- Accession number :
- edsair.doi.dedup.....f88f54369d0a65edd71956a74f236d9f