Cheng Chen1, Yanna Ba2, Deyang Li1, Xiaohong Du1, Xin Lia3, Hai Yang4, Jiaze An5, Jinliang Xing1, Hushan Yang6, Guanglong Dong7, Xu Guo8. 1. 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. 2. Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, 710032 Xi'an, China. 3. Department of Pain Treatment, 403 Clinical Department, 210 Hospital of PLA, 116021 Liaoning, China. 4. Dean's Office, Department of Training, The Fourth Military Medical University, 710032 Xi'an, China. 5. Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, 710032 Xi'an, China. 6. Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, 19107 Philadelphia, PA, USA. 7. Department of General Surgery, The General Hospital of PLA, 28, Fuxing Road, 100853 Beijing, China. Electronic address: guanglongdong@126.com. 8. 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.
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.
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: Teresa Aldámiz-Echevarría; Salvador Resino; José M Bellón; María A Jiménez-Sousa; Pilar Miralles; Luz M Medrano; Ana Carrero; Cristina Díez; Leire Pérez-Latorre; Chiara Fanciulli; Pilar Garcia-Broncano; Juan Berenguer Journal: J Transl Med Date: 2019-07-26 Impact factor: 5.531