Systematic identification of pathogenic variants of non-small cell lung cancer in the promoters of DNA-damage repair genes.

ABSTRACT:

Background

Deficiency in DNA-damage repair (DDR) genes, often due to disruptive coding variants, is linked to higher cancer risk. Our previous study has revealed the association between rare loss-of-function variants in DDR genes and the risk of lung cancer. However, it is still challenging to study the predisposing role of rare regulatory variants of these genes.

Methods

Based on whole-genome sequencing data from 2984 patients with non-small cell lung cancer (NSCLC) and 3020 controls, we performed massively parallel reporter assays on 1818 rare variants located in the promoters of DDR genes. Pathway- or gene-level burden analyses were performed using Firth's logistic regression or generalized linear model.

Findings

We identified 750 rare functional regulatory variant

SUBMITTER: An M 

PROVIDER: S-EPMC11663791 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature