title: A new functional IDH2 genetic variant is associated with the risk of lung cancer.
abstract: Recently, mutations in isocitrate dehydrogenase 1/2 (IDH1/2) were discovered in 70% of low-grade glioma and secondary glioblastoma multiforme. The discovery of an oncogenic function and the identification of onco-metabolites of IDH1/2 support new roles for metabolism in cancer. For example, some evidence indicates that IDH2 might also exhibit oncogenic functions by promoting cellular metabolism and cancer cell growth. We examined the association between IDH2 rs11540478 and lung cancer risk in 262 lung cancer patient cases and 602 healthy control subjects and also investigated the biological function of rs11540478 in vivo. We found that a higher risk was observed in lung cancer patient carriers of rs11540478 TT and CT compared with CC carriers (OR = 1.44; 95%CI = 1.04-2.00; P = 0.03). The frequency of IDH2 rs11540478 TT and CT carriers was decreased in healthy individuals between the ages of 50-77 compared to those aged 30-49 (OR = 0.67; 95%CI = 0.47-0.96; P = 0.03). Functional analysis showed the effect of rs11540478 on IDH2 expression and lung cancer cell viability, with higher IDH2 expression and cell viability among T allele compared with C allele. IDH2 mRNA was higher in peripheral blood lymphocytes from lung cancer patients compared to healthy subjects. Herein, for the first time we identified IDH2 rs11540478 as a new susceptibility locus for lung cancer. The effect of rs11540478 on mRNA expression of IDH2 and lung cancer cell viability might provide new insight for the genetic basis of lung cancer. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
authors.forename: Jiangjiang
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.|Department of Medical Oncology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Jingchen
authors.initials: J
authors.lastname: Lu
authors.affiliation: Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Medicine Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Medicine Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Clinical Laboratory, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Yuee
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.affiliation: Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
authors.forename: Xinxian
authors.initials: X
authors.lastname: Weng
authors.affiliation: Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Luo
authors.affiliation: Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.|Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Lunquan
authors.initials: L
authors.lastname: Sun
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, China.|Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.|Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000072283:A549 Cells; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase
keywords: IDH2; functional genetic variant; lung cancer