A variant of the Cockayne syndrome B gene ERCC6 confers risk of lung cancer

✍ Scribed by Zhongning Lin; Xuemei Zhang; Jingsheng Tuo; Yongli Guo; Bridgett Green; Chi-Chao Chan; Wen Tan; Ying Huang; Wenhua Ling; Fred F. Kadlubar; Dongxin Lin; Baitang Ning

• Book ID: 102261283
• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 300 KB
• Volume: 29
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.20610

✦ Synopsis

Cockayne syndrome B protein (ERCC6) plays an essential role in DNA repair. However, the Cockayne syndrome caused by the ERCC6 defect has not been linked to cancer predisposition; likely due to the fact that cells with severe disruption of the ERCC6 function are sensitive to lesion-induced apoptosis, thus reducing the chance of tumorigenesis. The biological function and cancer susceptibility of a common variant rs3793784:C4G (c.À6530C4G) in the ERCC6 was examined. We show that the c.À6530C allele has lower binding affinity of Sp1 by EMSA and displays a lower transcriptional activity in vitro and in vivo. We then examined the contribution of this polymorphism to the risk of lung cancer in a case-control study with 1,000 cases and 1,000 controls. The case-control analysis revealed a 1.76-fold (P 5 Â 10 À9 ) excess risk of developing lung cancer for the c.À6530CC carriers compared with noncarriers. The c.À6530CC interacts with smoking to intensify lung cancer risk, with the odds ratio (OR) 5 9 for developing lung cancer among heavy smokers. Our data constituted strong evidence that ERCC6 rs3793784:C4G alters its transcriptional activity and may confer personalized susceptibility to lung cancer.