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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.

The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract