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- Title
Pancreatic Ductal Carcinoma Risk Associated With Hereditary Cancer-Risk Genes.
- Authors
Gardiner, Anna; Kidd, John; Elias, Maria C; Young, Kayla; Mabey, Brent; Taherian, Nassim; Cummings, Shelly; Malafa, Mokenge; Rosenthal, Eric; Permuth, Jennifer B
- Abstract
<bold>Background: </bold>Although several hereditary cancer predisposition genes have been implicated in pancreatic ductal adenocarcinoma (PDAC) susceptibility, gene-specific risks are not well defined and are potentially biased because of the design of previous studies. More precise and unbiased risk estimates can result in screening and prevention better tailored to genetic findings.<bold>Methods: </bold>This is a retrospective analysis of 676 667 individuals, 2445 of whom had a personal diagnosis of PDAC, who received multigene panel testing between 2013 and 2020 from a single laboratory. Clinical data were obtained from test requisition forms. Multivariable logistic regression models determined the increased risk of PDAC because of pathogenic variants (PVs) in various genes as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Multivariable odds ratios were adjusted for age, personal and/or family cancer history, and ancestry.<bold>Results: </bold>Overall, 11.1% of patients with PDAC had a PV. Statistically significantly elevated PDAC risk (2-sided P < .05) was observed for CDK2NA (p16INK4a) (OR = 8.69, 95% CI = 4.69 to 16.12), ATM (OR = 3.44, 95% CI = 2.58 to 4.60), MSH2 (OR = 3.17, 95% CI = 1.70 to 5.91), PALB2 (OR = 3.09, 95% CI = 2.02 to 4.74), BRCA2 (OR = 2.55, 95% CI = 1.99 to 3.27), and BRCA1 (OR = 1.62, 95% CI = 1.07 to 2.43).<bold>Conclusions: </bold>This study provides PDAC risk estimates for 6 genes commonly included in multigene panel testing for hereditary cancer risk. These estimates are lower than those from previous studies, possibly because of adjustment for family history, and support current recommendations for germline testing in all PDAC patients, regardless of a personal or family history of cancer.
- Subjects
PANCREATIC tumors; GENETIC mutation; SOCIAL networks; RETROSPECTIVE studies; GENETIC testing; DUCTAL carcinoma; PSYCHOLOGICAL tests; DISEASE susceptibility; RESEARCH funding
- Publication
JNCI: Journal of the National Cancer Institute, 2022, Vol 114, Issue 7, p996
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djac069