The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract
Résumé
Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.
Mots clés
Carcinoma
Squamous Cell/*genetics Case-Control Studies Chromosomes
Human
Pair 12/*genetics Computer Simulation Demography Female *Genetic Loci *Genetic Predisposition to Disease Germ Cells Head and Neck Neoplasms/*genetics Humans Lung Neoplasms/genetics Male Middle Aged Physical Chromosome Mapping Polymorphism
Single Nucleotide/genetics Quantitative Trait Loci/genetics Rad52 DNA Repair and Recombination Protein/*genetics Risk Factors