A functional copy-number variation in MAPKAPK2 predicts risk and prognosis of lung cancer.

Abstract

Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) may promote cancer development and progression by inducing tumorigenesis and drug resistance. To assess whether the copy-number variation g.CNV-30450 located in the MAPKAPK2 promoter has any effect on lung cancer risk or prognosis, we investigated the association between g.CNV-30450 and cancer risk in three independent case-control studies of 2,332 individuals with lung cancer and 2,457 controls and the effects of g.CNV-30450 on cancer prognosis in 1,137 individuals with lung cancer with survival data in southern and eastern Chinese populations. We found that those subjects who had four copies of g.CNV-30450 had an increased cancer risk (odds ratio = 1.94, 95% confidence interval [CI] = 1.61-2.35) and a worse prognosis for individuals with lung cancer (with a median survival time of only 9 months) (hazard ratio = 1.47, 95% CI = 1.22-1.78) compared with those with two or three copies (with a median survival time of 14 months). Meanwhile, four copies of g.CNV-30450 significantly increased MAPKAPK2 expression, both in vitro and in vivo, compared with two or three copies. Our study establishes a robust association between the functional g.CNV-30450 in MAPKAPK2 and risk as well as prognosis of lung cancer, and it presents this functional copy-number variation as a potential biomarker for susceptibility to and prognosis for lung cancer.

• Authors: Bin Liu, Lei Yang, Binfang Huang, Mei Cheng, Hui Wang, Yinyan Li, Dongsheng Huang, Jian Zheng, Qingchu Li, Xin Zhang, Weidong Ji, Yifeng Zhou, Jiachun Lu
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 91 Issue 2 Pg. 384-90 (Aug 10 2012) ISSN: 1537-6605 [Electronic] United States
• PMID: 22883146 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Chemical References

• Genetic Markers
• Intracellular Signaling Peptides and Proteins
• MAP-kinase-activated kinase 2
• Protein Serine-Threonine Kinases

Topics

• Asian People (genetics)
• Case-Control Studies
• China (epidemiology)
• DNA Copy Number Variations (genetics)
• Genetic Markers
• Genetic Predisposition to Disease (genetics)
• Humans
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Lung Neoplasms (epidemiology, genetics)
• Odds Ratio
• Prognosis
• Promoter Regions, Genetic (genetics)
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Risk Factors