Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer.
Gastroenterology
; 148(3): 556-64, 2015 Mar.
Article
in En
| MEDLINE
| ID: mdl-25479140
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.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Esophageal Achalasia
/
Liver Transplantation
/
Nitric Oxide Synthase Type I
/
Genes, Neoplasm
/
Non-alcoholic Fatty Liver Disease
/
Hepatitis, Alcoholic
Type of study:
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Gastroenterology
Year:
2015
Type:
Article
Affiliation country:
Canada