Alterations in mtDNA: A qualitative and quantitative study associated with cervical cancer development

Warowicka, Alicja; Kwaśniewska, Anna; Goździcka-Józefiak, Anna

doi:10.1016/j.ygyno.2013.01.001

Cited by 34 publications

(41 citation statements)

References 33 publications

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“…In general, studies of mtDNA CN and risk of cancer have observed a positive association at various sites in prospective studies: lung (9, 16), cervix (11), colorectal (14, 17), and pancreas (15). One prospective study did not observe an overall association with gastric cancer risk in females but cases diagnosed within two years of blood draw had an increased risk, suggesting mtDNA CN elevation was an effect of the disease (19).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Copy Number and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Risk in Two Prospective Studies

Kim

Bassig

Seow

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication study in the Prostate, Lung, Colorectal, and Ovarian (PLCO) study and pooled with published ATBC (Alpha-Tocopherol, Beta-Carotene) data. Methods In PLCO, 292 NHL cases (95 CLL/SLL cases) and 301 controls were pooled with 142 NHL cases (47 CLL/SLL cases) and 142 controls from ATBC. Subjects answered a questionnaire and provided blood. DNA was extracted from pre-diagnostic peripheral white blood, and mtDNA CN assayed by quantitative polymerase chain reaction. Unconditional logistic regression estimated mtDNA CN and NHL risk by odds ratios (OR) and 95% confidence intervals (95% CI). Results Greater mtDNA CN was associated with increased risk of CLL/SLL among males in PLCO (3rd vs. 1st tertile: OR: 2.21; 95% CI: 1.03–4.72; p-trend: 0.049) and pooled (T3 vs. T1 OR: 3.12; 95% CI: 1.72–5.68; p-trend: 0.0002). Association was stronger among male smokers (p-trend: <0.0001) and essentially identical for cases diagnosed <6, >6–8, and >8 years from blood draw (pooled: p-interaction: 0.65). mtDNA CN and risk of other NHL subtypes and multiple myeloma showed no association. Conclusions and Impact Mitochondrial DNA CN was associated with risk of CLL/SLL in males/male smokers. The risk was observed among cases diagnosed as long as eight years after blood draw. These results suggest that higher mtDNA CN may reflect a process involved in CLL/SLL development.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Copy Number and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Risk in Two Prospective Studies

Kim

Bassig

Seow

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Mitochondrial aberrants, including mtDNA somatic mutations and copy number variations, have been frequently reported in various human cancers [13,21,24,32-35], including laryngeal cancer [19]. However, the prognostic value of copy number variations of mtDNA in laryngeal cancer patients remains to be explored.…”

Section: Discussionmentioning

confidence: 99%

Low copy number of mitochondrial DNA (mtDNA) predicts worse prognosis in early-stage laryngeal cancer patients

Dang

Wei

et al. 2014

Diagn Pathol

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ObjectivesAlterations in mitochondrial DNA (mtDNA) copy number have been widely reported in various human cancers, and been considered to be an important hallmark of cancers. However, little is known about the value of copy number variations of mtDNA in the prognostic evaluation of laryngeal cancer.Design and methodsUsing real-time quantitative PCR method, we investigated mtDNA copy number in a cohort of laryngeal cancers (n =204) and normal laryngeal tissues (n =40), and explored the association of variable mtDNA copy number with clinical outcomes of laryngeal cancer patients.ResultsOur data showed that the relative mean mtDNA content was higher in the laryngeal cancer patients (11.91 ± 4.35 copies) than the control subjects (4.72 ± 0.70 copies). Moreover, we found that mtDNA content was negatively associated with cigarette smoking (pack-years), tumor invasion, and TNM stage. Notably, variable mtDNA content did not affect overall survival of laryngeal cancer patients. However, when the patients were categorized into early-stage and late-stage tumor groups according to TNM stage, we found that low mtDNA content was strongly associated with poor survival in the former, but not in the latter.ConclusionsThe present study demonstrated that low mtDNA content was strongly correlated with some of clinicopathological characteristics, such as cigarette smoking, tumor invasion and TNM stage. In addition, we found a strong link between low mtDNA content and worse survival of the patients with early-stage tumors. Taken together, low copy number of mtDNA may be a useful poor prognostic factor for early-stage laryngeal cancer patients.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1841771572115955

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“…High levels of mtDNA copy with a 4.997 bp deletion in LSIL cells can be associated with the susceptibility of cells to an HPV-persistent infection and cervical cancer development (93). The copy number of mtDNA in cases which carried a D-loop mutation was significantly higher than that of the negative cases (P<0.05).…”

Section: Other Factors In Cervical Cancermentioning

confidence: 99%

IGF axis and other factors in HPV-related and HPV-unrelated carcinogenesis (Review)

Durzyńska

2014

Oncology Reports

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The insulin-like growth factor (IGF) axis promotes the growth of cells, tissues and organs. IGF-1 is mainly produced in the liver but is also secreted from local tissues. In the circulation, IGF-1 is bound to insulin-like binding proteins (IGFBPs), and when released it activates the insulin-like growth factor receptor (IGF-1R). The signal is further transmitted by intracellular signaling pathways leading to gene expression that regulates, among others, cell proliferation and survival. This review presents the IGF axis in the context of cell transformation and cancer development. Aspects involving IGF-1 deficiency and protection from cancer are also briefly described. Furthermore, human papillomaviruses (HPVs) interplaying with IGF axis components in cervical cancer development are described. These small dsDNA viruses are divided into low-risk and high-risk HPVs with regard to the potency of their oncogenic actions; they mainly infect epithelial or mucosal cells. Special attention is drawn to expression of two major HPV oncogenes (E6 and E7) initiating and maintaining cervical carcinogenesis, which is a multistep and multifactorial process; therefore, involvement of additional factors such as mitochondrial DNA changes, sex hormones, retinoic and folic acids are also discussed. Finally, IGF axis components and HPV oncogenes as targets in anticancer treatment are presented which include IGF-1R downregulation, RNA interference and anti-HPV therapeutic vaccines. The review concludes that despite an enormous advancement in research on IGF and HPV-related cancers, more molecular studies and clinical trials are needed before commercialized therapies are widely available for oncology patients.

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Alterations in mtDNA: A qualitative and quantitative study associated with cervical cancer development

Cited by 34 publications

References 33 publications

Mitochondrial DNA Copy Number and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Risk in Two Prospective Studies

Mitochondrial DNA Copy Number and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Risk in Two Prospective Studies

Low copy number of mitochondrial DNA (mtDNA) predicts worse prognosis in early-stage laryngeal cancer patients

IGF axis and other factors in HPV-related and HPV-unrelated carcinogenesis (Review)

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