Abstract
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.
Highlights
Upper aerodigestive tract (UADT) cancers, comprising of the oral cavity, larynx and esophagus, are the fourth most common cause of cancer death worldwide [1]
As observed in squamous cell carcinoma of the lung, the C allele was associated with a modest increase in upper aerodigestive tract (UADT) cancer risk (Fig. 1, p = 6x10−4), with the odds ratio (OR) for having one additional risk allele being 1.09 (95%confidence intervals (CIs): 1.04–1.15)
Our study has identified rs10849605 to be associated with UADT cancer (p = 6x10−4)
Summary
Upper aerodigestive tract (UADT) cancers, comprising of the oral cavity, larynx and esophagus, are the fourth most common cause of cancer death worldwide [1]. While consumption of tobacco and alcohol are the main UADT cancers risk factors [2], genetic susceptibility has been hypothesized to play a role in the pathogenesis of this disease [3,4]. Exposure to tobacco and alcohol leads to cell damage and DNA alterations that, in the absence of appropriate repair, may cause cell cycle deregulation and cancer development [5,6]. The aim of the present study was to investigate RAD52 in the context of genetic susceptibility to SCC of the UADT, to explore how this association might be mediated and examine the somatic mutation events at the RAD52 12p13.33 locus
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