title: Genetic variations of mitochondrial genome modify risk and prognosis of hepatocellular carcinoma patients.
abstract: BACKGROUND
  Previous studies have indicated that mitochondrial genetic variations were associated with the risk of many cancers. However, there are few reports on the association between single nucleotide polymorphisms (SNPs) or haplogroups of mitochondrial DNA (mtDNA) and the risk or prognosis of hepatocellular carcinoma (HCC).
  
  
  METHODS
  In order to investigate the predictive and prognostic role of mtDNA SNPs and haplogroups in HCC, the mitochondrial genome of 188 HCC patients and 344 healthy controls were sequenced by next generation sequencing technology. Then, logistic regression analysis was used to determine the effect of mtDNA SNP or haplogroup on risk and prognosis of HCC patients.
  
  
  RESULTS
  The haplogroup M7 had an odds ratio (OR) of 0.47 (95% CI=0.24-0.91; P=0.026) to develop HCC. The frequency of 152T/C, 199T/C, 4048G/A, 9824T/C, 15784T/C, 16185C/T and 16399A/G was significantly different between HCC patients and the controls. In addition, multivariate analysis with COX hazards model showed that the patients with haplogroup M8 had lower survival rate than the patients with haplogroup D4 (HR=2.62, 95% CI=1.03-6.68; P=0.044). Three SNPs 15784T/C, 16185C/T and 16399A/G were also identified to have a statistically significant association with postoperative survival in HCC.
  
  
  CONCLUSIONS
  To date, these results provide the first evidence that mtDNA SNPs and haplogroups may be potential risk factors for susceptibility and survival of HCC patients.
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, The Fourth Military Medical University, 169, Changle West Road, 710032 Xi'an, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Ba
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, The Fourth Military Medical University, 169, Changle West Road, 710032 Xi'an, China.
authors.forename: Deyang
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, The Fourth Military Medical University, 169, Changle West Road, 710032 Xi'an, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Pain Treatment, 403 Clinical Department, 210 Hospital of PLA, 116021 Liaoning, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lia
authors.affiliation: Dean's Office, Department of Training, The Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, 710032 Xi'an, China.
authors.forename: Jiaze
authors.initials: J
authors.lastname: An
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, The Fourth Military Medical University, 169, Changle West Road, 710032 Xi'an, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
authors.affiliation: Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, 19107 Philadelphia, PA, USA.
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The General Hospital of PLA, 28, Fuxing Road, 100853 Beijing, China. Electronic address: guanglongdong@126.com.
authors.forename: Guanglong
authors.initials: G
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, The Fourth Military Medical University, 169, Changle West Road, 710032 Xi'an, China. Electronic address: fmmuxguo@163.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Guo
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality; D005260:Female; D014644:Genetic Variation; D054629:Genome, Mitochondrial / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018570:Risk Assessment; D015996:Survival Rate