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Gastroenterology. 2015 Mar;148(3):556-64. doi: 10.1053/j.gastro.2014.11.042. Epub 2014 Dec 2.

Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer.

Author information

1
Ontario Institute for Cancer Research, Canada; Department of Medicine, University of Toronto, Canada.
2
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Canada.
3
Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada.
4
Laboratory Medicine and Pathobiology, University of Toronto, Canada.
5
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
6
Ontario Institute for Cancer Research, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Canada; Pathology and Laboratory Medicine, Mount Sinai Hospital, Canada.
7
Ontario Institute for Cancer Research, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada. Electronic address: steven.gallinger@uhn.on.ca.

Abstract

BACKGROUND & AIMS:

We investigated the prevalence of germline mutations in APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53 in patients with pancreatic cancer.

METHODS:

The Ontario Pancreas Cancer Study enrolls consenting participants with pancreatic cancer from a province-wide electronic pathology database; 708 probands were enrolled from April 2003 through August 2012. To improve the precision of BRCA2 prevalence estimates, 290 probands were selected from 3 strata, based on family history of breast and/or ovarian cancer, pancreatic cancer, or neither. Germline DNA was analyzed by next-generation sequencing using a custom multiple-gene panel. Mutation prevalence estimates were calculated from the sample for the entire cohort.

RESULTS:

Eleven pathogenic mutations were identified: 3 in ATM, 1 in BRCA1, 2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53. The prevalence of mutations in all 13 genes was 3.8% (95% confidence interval, 2.1%-5.6%). Carrier status was associated significantly with breast cancer in the proband or first-degree relative (P < .01), and with colorectal cancer in the proband or first-degree relative (P < .01), but not family history of pancreatic cancer, age at diagnosis, or stage at diagnosis. Of patients with a personal or family history of breast and colorectal cancer, 10.7% (95% confidence interval, 4.4%-17.0%) and 11.1% (95% confidence interval, 3.0%-19.1%) carried pathogenic mutations, respectively.

CONCLUSIONS:

A small but clinically important proportion of pancreatic cancer is associated with mutations in known predisposition genes. The heterogeneity of mutations identified in this study shows the value of using a multiple-gene panel in pancreatic cancer.

KEYWORDS:

Cancer Risk; Familial Pancreatic Cancer; Pancreatic Cancer Genetics

Comment on

  • Gastroenterology. 2015 Mar;148(3):459-61.
PMID:
25479140
PMCID:
PMC4339623
DOI:
10.1053/j.gastro.2014.11.042
[Indexed for MEDLINE]
Free PMC Article

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