Pancreatic Ductal Carcinoma Risk Associated with Hereditary Cancer-Risk Genes
Menée sur la période 2013-2020 auprès de 676 667 personnes ayant réalisé un test multigénique, cette étude identifie 6 variants de gènes couramment inclus dans les tests génétiques et associés au risque d'adénocarcinome canalaire du pancréas (2 445 cas)
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 due to the design of previous studies. More precise and unbiased risk estimates can result in screening and prevention better tailored to genetic findings.This is a retrospective analysis of 676,667 individuals, 2,445 of whom had a personal diagnosis of PDAC, who received multigene panel testing between 2013–2020 from a single laboratory. Clinical data were obtained from test requisition forms. Multivariable logistic regression models determined the increased risk of PDAC due to pathogenic variants (PVs) in various genes as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Multivariable odds ratios were adjusted for age, personal/family cancer history, and ancestry.Overall, 11.1% of patients with PDAC had a PV. Significantly elevated PDAC risk (two-sided P < .05) was observed for CDK2NA (p16INK4a) (OR 8.69, 95% CI 4.69–16.12), ATM (OR 3.44, 95% CI 2.58–4.60), MSH2 (OR 3.17, 95% CI 1.70–5.91), PALB2 (OR 3.09, 95% CI 2.02–4.74), BRCA2 (OR 2.55, 95% CI 1.99–3.27), and BRCA1 (OR 1.62, 95% CI 1.07–2.43).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 due to adjustment for family history, and support current recommendations for germline testing in all PDAC patients, regardless of a personal or family history of cancer.
Journal of the National Cancer Institute , article en libre accès, 2021