12p13.33/RAD52基因座与上消化道鳞状细胞癌的遗传易感性
The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract.
作者信息
Delahaye-Sourdeix Manon, Oliver Javier, Timofeeva Maria N, Gaborieau Valérie, Johansson Mattias, Chabrier Amélie, Wozniak Magdalena B, Brenner Darren R, Vallée Maxime P, Anantharaman Devasena, Lagiou Pagona, Holcátová Ivana, Richiardi Lorenzo, Kjaerheim Kristina, Agudo Antonio, Castellsagué Xavier, Macfarlane Tatiana V, Barzan Luigi, Canova Cristina, Thakker Nalin S, Conway David I, Znaor Ariana, Healy Claire M, Ahrens Wolfgang, Zaridze David, Szeszenia-Dabrowska Neonilia, Lissowska Jolanta, Fabianova Eleonora, Mates Ioan Nicolae, Bencko Vladimir, Foretova Lenka, Janout Vladimir, Curado Maria Paula, Koifman Sergio, Menezes Ana, Wünsch-Filho Victor, Eluf-Neto José, Boffetta Paolo, Garrote Leticia Fernández, Serraino Diego, Lener Marcin, Jaworowska Ewa, Lubiński Jan, Boccia Stefania, Rajkumar Thangarajan, Samant Tanuja A, Mahimkar Manoj B, Matsuo Keitaro, Franceschi Silvia, Byrnes Graham, Brennan Paul, McKay James D
机构信息
Genetic Cancer Susceptibility group (GCS), International Agency for Research on Cancer (IARC), Lyon, France.
Genetic Epidemiology group (GEP), International Agency for Research on Cancer (IARC), Lyon, France; Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council (MRC) Human Genetics Unit, Edinburgh, United Kingdom.
出版信息
PLoS One. 2015 Mar 20;10(3):e0117639. doi: 10.1371/journal.pone.0117639. eCollection 2015.
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.
位于12p13.33/RAD52基因座内的基因变异已被证实与肺鳞状细胞癌（LUSC）有关。在此，我们对来自9项不同研究的5947例上消化道（UADT）癌患者和7789例对照进行研究，发现rs10849605（RAD52基因常见的内含子变异）也与上消化道鳞状细胞癌病例相关（比值比=1.09，95%置信区间：1.04 - 1.15，p = 6×10⁻⁴）。我们还确定rs10849605是UADT（p = 1×10⁻³）和LUSC（p = 9×10⁻⁴）肿瘤中的RAD52顺式作用表达数量性状基因座，UADT/LUSC风险等位基因与RAD52表达水平升高相关。包含rs10849605/RAD52的12p13.33基因座在UADT（n = 374，q值 = 0.075）和LUSC（n = 464，q值 = 0.007）肿瘤中被鉴定为显著的体细胞局灶性拷贝数扩增，并且与更高的RAD52肿瘤表达水平相关（在UADT和LUSC中分别为p = 6×10⁻⁴⁸和p = 3×10⁻²⁹）。综合来看，这些结果表明RAD52表达增加在UADT和LUSC肿瘤的遗传易感性和肿瘤发生中均起作用。
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