Analysis of mitochondrial DNA in Tibetan gastric cancer patients at high altitude

Jiang,Jun; Zhao,Jun‑Hui; Wang,Xue‑Lian; Di,Ji; Liu,Zhi‑Bo; Li,Guo‑Yuan; Wang,Miao‑Zhou; Li,Yan; Chen,Rong; Ge,Ri‑Li

doi:10.3892/mco.2015.539

Analysis of mitochondrial DNA in Tibetan gastric cancer patients at high altitude

Authors:
- Jun Jiang
- Jun‑Hui Zhao
- Xue‑Lian Wang
- Ji Di
- Zhi‑Bo Liu
- Guo‑Yuan Li
- Miao‑Zhou Wang
- Yan Li
- Rong Chen
- Ri‑Li Ge
View Affiliations

Affiliations: Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai 810001, P.R. China, Department of Oncology, Affiliated Hospital of Qinghai University, Xining, Qinghai 810001, P.R. China, Department of Surgery, Affiliated Hospital of Qinghai University, Xining, Qinghai 810001, P.R. China
Published online on: April 3, 2015 https://doi.org/10.3892/mco.2015.539
Pages: 875-879

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The highest risk areas of gastric cancer are currently Japan, Korea and China; Qinghai, a high‑altitude area, has one of the highest gastric cancer rates in China. The incidence of gastric cancer is higher in the Tibetan ethnic group compared to that in the Han ethnic group in Qinghai. This study was conducted to determine the clinical characteristics of mitochondrial DNA (mtDNA) mutations and copy numbers among Tibetans with gastric cancer residing at high altitudes and investigate the association between adaptations to hypoxic conditions and oncogenesis. A total of 23 Tibetan gastric cancer patients and 40 matched controls were recruited in this study. Leukocyte mtDNA genes and copy numbers were analyzed. The haplogroups were classified based on mitochondrial gene sequences. A total of 56.5% of the study participants had used alcohol at some point in their lives and 73.9% were positive for Helicobacter pylori (H. pylori). Eight mutations in 8 mitochondrial genes were identified in 43.4% of the Tibetan cancer patient group. There were no significant differences in leukocyte mtDNA copy number levels based on smoking status, alchohol consumption, obesity or H. pylori infection between the control and cancer groups. Statistical differences were also not found between gastric cancer patients with and those without mtDNA mutations. The majority of Tibetan patients with gastric cancer belonged to the mitochondrial haplogroup M9. In conclusion, Tibetans with gastric cancer residing at high altitudes exhibited a wide spectrum of mtDNA mutations. However, leukocyte mtDNA copy numbers in stage II gastric cancer were not statistically different compared to those in healthy Tibetans.

View Figures

View References

1	Ahn HS, Yook JH, Park CH, et al: General perioperative management of gastric cancer patients at high-volume centers. Gastric Cancer. 14:178–182. 2011. View Article : Google Scholar : PubMed/NCBI
2	Malekzadeh R, Derakhshan MH and Malekzadeh Z: Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med. 12:576–583. 2009.PubMed/NCBI
3	Hung WY, Wu CW, Yin PH, et al: Somatic mutations in mitochondrial genome and their potential roles in the progression of human gastric cancer. Biochim Biophys Acta. 1800:264–270. 2010. View Article : Google Scholar : PubMed/NCBI
4	Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL and Trotti A: AJCC Cancer Staging Manual. 7th. Springer; New York, NY: 2010
5	van Oven M and Kayser M: Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat. 30:E386–E394. 2009. View Article : Google Scholar : PubMed/NCBI
6	Fan L and Yao YG: An update to MitoTool: using a new scoring system for faster mtDNA haplogroup determination. Mitochondrion. 13:360–363. 2013. View Article : Google Scholar : PubMed/NCBI
7	Xing J, Chen M, Wood CG, et al: Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma. J Natl Cancer Inst. 100:1104–1112. 2008. View Article : Google Scholar : PubMed/NCBI
8	Liao LM, Baccarelli A, Shu XO, et al: Mitochondrial DNA copy number and risk of gastric cancer: a report from the Shanghai Women's Health Study. Cancer Epidemiol Biomarkers Prev. 20:1944–1949. 2011. View Article : Google Scholar : PubMed/NCBI
9	Munakata K, Tanaka M, Mori K, Washizuka S, et al: Mitochondrial DNA 3644T→C mutation associated with bipolar disorder. Genomics. 84:1041–1050. 2004. View Article : Google Scholar : PubMed/NCBI
10	Jones JB, Song JJ, Hempen PM, Parmigiani G, Hruban RH and Kern SE: Detection of mitochondrial DNA mutations in pancreatic cancer offers a ‘mass’-ive advantage over detection of nuclear DNA mutations. Cancer Res. 61:1299–1304. 2001.PubMed/NCBI
11	Porcelli AM, Ghelli A, Ceccarelli C, et al: The genetic and metabolic signature of oncocytic transformation implicates HIF1alpha destabilization. Hum Mol Genet. 19:1019–1032. 2010. View Article : Google Scholar : PubMed/NCBI
12	Elstner M, Schmidt C, Zingler VC, et al: Mitochondrial 12S rRNA susceptibility mutations in aminoglycoside-associated and idiopathic bilateral vestibulopathy. Biochem Biophys Res Commun. 377:379–383. 2008. View Article : Google Scholar : PubMed/NCBI
13	Okura T, Koda M, Ando F, Niino N, Tanaka M and Shimokata H: Association of the mitochondrial DNA 15497G/A polymorphism with obesity in a middle-aged and elderly Japanese population. Hum Genet. 113:432–436. 2003. View Article : Google Scholar : PubMed/NCBI
14	Fauser S, Luberichs J, Besch D and Leo-Kottler B: Sequence analysis of the complete mitochondrial genome in patients with Leber's hereditary optic neuropathy lacking the three most common pathogenic DNA mutations. Biochem Biophys Res Commun. 295:342–347. 2002. View Article : Google Scholar : PubMed/NCBI
15	Petros JA, Baumann AK, Ruiz-Pesini E, et al: mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA. 102:719–724. 2005. View Article : Google Scholar : PubMed/NCBI
16	Wu CW, Yin PH, Hung WY, et al: Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer. 44:19–28. 2005. View Article : Google Scholar : PubMed/NCBI
17	Han CB, Li F, Zhao YJ, et al: Variations of mitochondrial D-loop region plus downstream gene 1 2S rRNA-tRNA^PHE and gastric carcinomas. World J Gastroenterol. 9:1925–1929. 2003.PubMed/NCBI
18	Fliss MS, Usadel H, Caballero OL, et al: Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science. 287:2017–2019. 2000. View Article : Google Scholar : PubMed/NCBI
19	Pereira L, Soares P, Radivojac P, Li B and Samuels DC: Comparing phylogeny and the predicted pathogenicity of protein variations reveals equal purifying selection across the global human mtDNA diversity. Am J Hum Genet. 88:433–439. 2011. View Article : Google Scholar : PubMed/NCBI
20	Maximo V, Soares P, Seruca R, Rocha AS, Castro P and Sobrinho-Simoes M: Microsatellite instability, mitochondrial DNA large deletions, and mitochondrial DNA mutations in gastric carcinoma. Genes Chromosomes Cancer. 32:136–143. 2001. View Article : Google Scholar : PubMed/NCBI
21	Brandon M, Baldi P and Wallace DC: Mitochondrial mutations in cancer. Oncogene. 25:4647–4662. 2006. View Article : Google Scholar : PubMed/NCBI
22	Gu M, Dong X, Shi L, et al: Differences in mtDNA whole sequence between Tibetan and Han populations suggesting adaptive selection to high altitude. Gene. 496:37–44. 2012. View Article : Google Scholar : PubMed/NCBI
23	Shen J, Platek M, Mahasneh A, Ambrosone CB and Zhao H: Mitochondrial copy number and risk of breast cancer: a pilot study. Mitochondrion. 10:62–68. 2010. View Article : Google Scholar : PubMed/NCBI
24	Thyagarajan B, Wang R, Nelson H, Barcelo H, Koh WP and Yuan JM: Mitochondrial DNA copy number is associated with breast cancer risk. PLoS One. 8:e659682013. View Article : Google Scholar : PubMed/NCBI