Association study of genetic variation in DNA repair pathway genes and risk of basal cell carcinoma

A partir de données d'études d'association sur le génome entier incluant 17 187 patients atteints d'un carcinome basocellulaire et 287 054 témoins, cette méta-analyse évalue l'association entre des polymorphismes de gènes impliqués dans les processus de réparation de l'ADN et le risque de développer la maladie

Résumé en anglais

DNA repair plays a critical role in protecting the genome from ultraviolet radiation and maintaining the genomic integrity of cells. Genetic variants in DNA repair-related genes can influence an individual's DNA repair capacity, which may be related to the risk of developing basal cell carcinoma (BCC). We comprehensively assessed the associations of 2,965 independent single-nucleotide polymorphisms (SNPs) across 165 DNA repair pathway genes with BCC risk in a genome-wide association meta-analysis totaling 17,187 BCC cases and 287,054 controls from two data sets. After multiple testing corrections, we identified three SNPs (rs2805831 upstream of XPA: OR = 0.93, P = 1.35 × 10−6; rs659857 in exon of MUS81: OR = 1.06, P = 3.09 × 10−6 and rs57343616 in 3′ UTR of NABP2: OR = 1.11, P = 6.47 × 10−6) as significantly associated with BCC risk in meta-analysis, and all of them were nominally significant in both data sets. Furthermore, rs659857 [T] was significantly associated with decreased expression of MUS81 mRNA in the expression quantitative trait locus (eQTL) analysis. Our findings suggest that the inherited common variation in three DNA repair genes—XPA, MUS81 and NABP2—may be involved in the development of BCC. To our knowledge, our study is the first report thoroughly examining the effects of SNPs across DNA repair pathway genes on BCC risk based on a genome-wide association meta-analysis.