Association of Germline Pathogenic Variants in

Document Type

Article

Publication Date

1-1-2025

Publication Title

JCO Precis Oncol

Abstract

PURPOSE: Although lung cancer is one of the most common malignancies, the underlying genetics regarding susceptibility remain poorly understood. We characterized the spectrum of pathogenic/likely pathogenic (P/LP) germline variants within DNA damage response (DDR) genes among lung cancer cases and controls in non-Hispanic Whites (NHWs) and African Americans (AAs).

MATERIALS AND METHODS: Rare, germline variants in 67 DDR genes with evidence of pathogenicity were identified using the ClinVar database. These P/LP variants were genotyped in a sample of 3,040 lung cancer cases and controls from the Inflammation, Health, Ancestry, and Lung Epidemiology study (NHW: n = 1,915; AA: n = 1,125) and were tested for their association with lung cancer using multivariate logistic regression adjusting for age, sex, pack-years, and race.

RESULTS: We identified 49 unique rare P/LP variants in 21 genes among 156 carriers. Approximately 5.9% of lung cancer cases and 4.2% of controls carried at least one P/LP variant. P/LP variants in DDR genes were more common in lung cancer cases, particularly those diagnosed with adenocarcinoma (odds ratio [OR], 1.46 [95% CI, 1.00 to 2.14]).

CONCLUSION: Germline variants in DDR genes appear to be associated with lung cancer, particularly when examined by gene subtype and morphologic subtype.

Medical Subject Headings

Humans; Lung Neoplasms; DNA Glycosylases; Male; Female; Black or African American; White People; Middle Aged; Aged; Germ-Line Mutation; DNA Damage; Genetic Predisposition to Disease; Case-Control Studies

PubMed ID

39854657

Volume

9

First Page

2400558

Last Page

2400558

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