| Literature DB >> 25640678 |
Donghai Xiong1, Yian Wang1, Elena Kupert2, Claire Simpson3, Susan M Pinney4, Colette R Gaba5, Diptasri Mandal6, Ann G Schwartz7, Ping Yang8, Mariza de Andrade8, Claudio Pikielny9, Jinyoung Byun9, Yafang Li9, Dwight Stambolian10, Margaret R Spitz11, Yanhong Liu11, Christopher I Amos9, Joan E Bailey-Wilson3, Marshall Anderson2, Ming You12.
Abstract
PARK2, a gene associated with Parkinson disease, is a tumor suppressor in human malignancies. Here, we show that c.823C>T (p.Arg275Trp), a germline mutation in PARK2, is present in a family with eight cases of lung cancer. The resulting amino acid change, p.Arg275Trp, is located in the highly conserved RING finger 1 domain of PARK2, which encodes an E3 ubiquitin ligase. Upon further analysis, the c.823C>T mutation was detected in three additional families affected by lung cancer. The effect size for PARK2 c.823C>T (odds ratio = 5.24) in white individuals was larger than those reported for variants from lung cancer genome-wide association studies. These data implicate this PARK2 germline mutation as a genetic susceptibility factor for lung cancer. Our results provide a rationale for further investigations of this specific mutation and gene for evaluation of the possibility of developing targeted therapies against lung cancer in individuals with PARK2 variants by compensating for the loss-of-function effect caused by the associated variation.Entities:
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Year: 2015 PMID： 25640678 PMCID： PMC4320264 DOI： 10.1016/j.ajhg.2014.12.016
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025