Association of Leukocyte Mitochondrial DNA Copy Number with Colorectal Cancer Risk: Results from the Shanghai Women's Health Study

Huang, Bo; Gao, Yu‐Tang; Shu, Xiao‐Ou; Wen, Wanqing; Yang, Gong; Li, Guoliang; Courtney, Regina; Ji, Bu‐Tian; Li, Honglan; Purdue, Mark P.; Wang, Zheng; Cai, Qiuyin

doi:10.1158/1055-9965.epi-14-0297

Cited by 36 publications

(24 citation statements)

References 35 publications

(35 reference statements)

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“…Our analysis included 36 studies that focused on diverse cancer types from different origins around the world 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 . To reduce the uncertainty induced by confusing factors in the meta-analysis, we evaluated the association between mtDNA content with cancer risk in an overall analysis, as well as stratified analyses by cancer types, genders, ages, ethnicity and life styles.…”

Section: Discussionmentioning

confidence: 99%

Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

Yao

Shen

2016

Sci Rep

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Accumulating epidemiological evidence indicates that the quantitative changes in human mitochondrial DNA (mtDNA) copy number could affect the genetic susceptibility of malignancies in a tumor-specific manner, but the results are still elusive. To provide a more precise estimation on the association between mtDNA copy number and risk of diverse malignancies, a meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95% confidence intervals (95% CI). A total of 36 case-control studies involving 11,847 cases and 15,438 controls were finally included in the meta-analysis. Overall analysis of all studies suggested no significant association between mtDNA content and cancer risk (OR = 1.044, 95% CI = 0.866–1.260, P = 0.651). Subgroup analyses by cancer types showed an obvious positive association between mtDNA content and lymphoma and breast cancer (OR = 1.645, 95% CI = 1.117–2.421, P = 0.012; OR = 1.721, 95% CI = 1.130–2.622, P = 0.011, respectively), and a negative association for hepatic carcinoma. Stratified analyses by other confounding factors also found increased cancer risk in people with drinking addiction. Further analysis using studies of quartiles found that populations with the highest mtDNA content may be under more obvious risk of melanoma and that Western populations were more susceptible than Asians.

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Section: Discussionmentioning

confidence: 99%

Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

Yao

Shen

2016

Sci Rep

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“…Epidemiological studies have indicated significant association of leukocyte mtDNA copy number with risk of several malignancies, including glioma, colorectal and breast tumors, and its use has been proposed as a potential biomarker to select patients who benefit from adjuvant chemotherapy [46][47][48][49][50]. A reduced mtDNA content has also been correlated with lymph node metastasis and lower survival rates in patients with colorectal cancer [51].…”

Section: Mtdna Copy Number Alterationsmentioning

confidence: 99%

Mitochondrial DNA Variations in Tumors: Drivers or Passengers?

Errichiello¹,

Venesio²

2018

Mitochondrial DNA - New Insights

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Mitochondrial DNA alterations, including point mutations, deletions, inversions and copy number variations, have been widely reported in many age-related degenerative diseases and tumors. However, numerous studies investigating their pathogenic role in cancer have provided inconsistent evidence. Furthermore, biological impacts of mitochondrial DNA variants vary tremendously, depending on the proportion of mutant DNA molecules carried by the neoplastic cells (the so-called heteroplasmy). The recent discovery of inter-genomic crosstalk between nucleus and mitochondria has reinforced the role of mitochondrial DNA variants in perturbing this essential signaling pathway and thus indirectly targeting nuclear genes involved in tumorigenic and invasive phenotype. Therefore, mitochondrial dysfunction is currently considered a crucial hallmark of carcinogenesis as well as a promising target for anticancer therapy. This chapter describes the role of different types of mitochondrial DNA alterations by mainly considering the paradigmatic model of colorectal carcinogenesis and, in particular, it revisits the issue of whether mitochondrial mutations are causative cancer drivers or simply genuine passenger events. The advent of high-throughput next-generation sequencing techniques, as well as the development of genetic and pharmaceutical interventions for the treatment of mitochondrial dysfunction in cancer, are also discussed.

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“…Epidemiologic studies in the past decade have demonstrated a statistically significant positive association between mitochondrial DNA (mtDNA) copy number measured in whole blood DNA and risks of various types of cancer, including melanoma, lung cancer, renal cell carcinoma, breast cancer, chronic lymphocytic leukemia, non-Hodgkin lymphoma, colorectal cancer, glioma, and pancreatic cancer [11][12][13][14][15][16][17][18][19]. However, a reverse association is also reported in a few studies, including kidney and colorectal cancers [20,21]. To date, the underlying molecular mechanism between mtDNA copy number in whole blood and cancer risk is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA copy number in whole blood and glioma risk: A case control study

Shen

Song

et al. 2016

Molecular Carcinogenesis

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Alterations in mitochondrial DNA (mtDNA) copy number are observed in human gliomas. However, whether variations in mtDNA copy number in whole blood play any role in glioma carcinogenesis is still largely unknown. In current study with 395 glioma patients and 425 healthy controls, we intended to investigate the association between mtDNA copy number in whole blood and glioma risk. Overall, we found that levels of mtDNA copy number were significantly higher in glioma cases than healthy controls (mean: 1.48 vs. 1.32, P < 0.01). In both cases and controls, levels of mtDNA copy number were inversely correlated with age (P < 0.01, respectively). And in cases, newly diagnosed, glioblastoma (GBM), and high grade glioma patients had significantly lower mtDNA copy number than their counterparts (P = 0.02, P < 0.01, and P = 0.04, respectively). In the multivariate analysis, elevated mtDNA copy number levels were associated with a 1.63-fold increased risk of glioma (adjusted odds ratio (OR) = 1.63, 95% confidence interval (CI) = 1.23-2.14). In further quartile analysis, study subjects who had highest levels of mtNDA copy number had 1.75-fold increased risk of gliomas (adjOR = 1.75, 95%CI = 1.18-2.61). In brief, our findings support the role of mtDNA copy number in the glioma carcinogenesis. © 2016 Wiley Periodicals, Inc.

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Association of Leukocyte Mitochondrial DNA Copy Number with Colorectal Cancer Risk: Results from the Shanghai Women's Health Study

Cited by 36 publications

References 35 publications

Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

Mitochondrial DNA Variations in Tumors: Drivers or Passengers?

Mitochondrial DNA copy number in whole blood and glioma risk: A case control study

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