Mitochondrial copy number and risk of breast cancer: A pilot study

Shen, Jie; Platek, Mary E.; Mahasneh, Amjad; Ambrosone, Christine B.; Zhao, Hua

doi:10.1016/j.mito.2009.09.004

Cited by 141 publications

(117 citation statements)

References 39 publications

(48 reference statements)

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“…The evidence regarding the association between mtDNA copy numbers in peripheral blood cells (PBC) and risk of breast cancer is also limited. In a retrospective study with postdiagnostic blood samples including 103 case-control pairs, Shen and colleagues (8) found that high mtDNA copy number in PBCs was associated with increased risk of breast cancer, and several endogenous oxidants and antioxidants. A small prospective study of 183 breast cancer cases and 529 controls in China also found a similar association with breast cancer risk; however, data suggested that the association was present only in samples collected close to diagnosis (9).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer

et al. 2015

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Increased mitochondrial DNA (mtDNA) copy number in peripheral blood cells (PBC) has been associated with the risk of developing several tumor types. Here we evaluate sources of variation of this biomarker and its association with breast cancer risk in a prospective cohort study. mtDNA copy number was measured using quantitative real-time PCR on PBC DNA samples from participants in the UK-based Breakthrough Generations Study. Temporal and assay variation was evaluated in a serial study of 91 women, with two blood samples collected approximately 6-years apart. Then, associations with breast cancer risk factors and risk were evaluated in 1,108 cases and 1,099 controls using a nested case-control design. In the serial study, mtDNA copy number showed low assay variation but large temporal variation [assay intraclass correlation coefficient (ICC), 79.3%-87.9%; temporal ICC, 38.3%). Higher mtDNA copy number was significantly associated with younger age at blood collection, being premenopausal, having an older age at menopause, and never taking HRT, both in cases and controls. Based on measurements in a single blood sample taken on average 6 years before diagnosis, higher mtDNA copy number was associated with increased breast cancer risk [OR (95% CI) for highest versus lowest quartile, 1.37 (1.02-1.83); P trend ¼ 0.007]. In conclusion, mtDNA copy number is associated with breast cancer risk and represents a promising biomarker for risk assessment. The relatively large temporal variation should be taken into account in future analyses. Cancer Res; 75(14); 2844-50. Ó2015 AACR.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer

et al. 2015

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“…However, two epidemiological studies that investigated whole blood and buffy coat specimens demonstrated a positive association between mtDNA levels and breast cancer risk (Shen et al, 2010;Thyagarajan et al, 2013). Associations between mtDNA alterations and clinicopathological features of breast cancer have also been inconsistent across studies (Yu et al, 2007;Fan et al, 2009;Xia et al, 2009a).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Levels in Blood and Tissue Samples from Breast Cancer Patients of Different Stages

Xia

Wang²,

Geng³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Aims: Alterations in mitochondrial DNA (mtDNA) have been implicated in carcinogenesis and tumor progression. We here evaluated the diagnostic and prognostic potential of mtDNA as a biomarker for breast cancer. Methods: Using multiplex real-time polymerase chain reaction, nuclear DNA (nDNA) and mtDNA levels in serum, buffy coat, tumor, and tumor-adjacent tissue samples from 50 breast cancer patients were determined and assessed for associations with clinicopathological features. To evaluate mtDNA as a biomarker for distinguishing between the four sample types, we created receiver operating characteristic (ROC) curves. Results: The mtDNA levels in buffy coat were significantly lower than in other sample types. Relative to tumor-adjacent tissue, reduced levels of mtDNA were identified in buffy coat and tumor tissue but not in serum. According to ROC curve analysis, mtDNA levels could be used to distinguish between buffy coat and tumor-adjacent tissue samples with good sensitivity (77%) and specificity (83%). Moreover, mtDNA levels in serum and tumor tissue were positively associated with cancer TMN stage. Conclusions: The mtDNA levels in blood samples may represent a promising, non-invasive biomarker in breast cancer patients. Additional, large-scale validation studies are required to establish the potential use of mtDNA levels in the early diagnosis and monitoring of breast cancer.

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“…The leukocyte mtDNA copy number has been investigated in several types of cancer (7,23,24). Several studies observed that a higher cancer risk is likely accompanied by an increase in the mtDNA copy number (21).…”

Section: Discussionmentioning

confidence: 99%

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

Jiang

Zhao

Wang

et al. 2015

Molecular and Clinical Oncology

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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. IntroductionDespite a sharp decline in the incidence and mortality rates of gastric cancer, this condition remains the second leading cause of cancer-related mortality worldwide, following lung cancer. Gastric cancer is frequently diagnosed at an advanced stage. The 5-year survival rate is ~20% in developing countries (1). There is a wide variation in the incidence of gastric cancer in different geographical regions. The highest risk areas with an age-standardized incidence rate are Japan, Korea and China (2). The distribution of gastric cancer is not uniform across China. In particular, gastric cancer is the leading type of cancer in Qinghai, a high-altitude area in Northwest China. Moreover, the Chinese National Cancer Center in 2012 reported that Qinghai has one of the highest rates of gastric cancer in China. The incidence of gastric cancer is higher in the Tibetan compared to that in the Han ethnic group in Qinghai, a finding that has attracted significant attention over the last few years.The marked variation of gastric cancer risk in different geographical areas and the striking differences in potential environmental risk factors between regions prompted the investigation of gastric cancer etiology. Mitochondria are semi-autonomous organelles within cells that play an essential role in cellular energy metabolism, generation of...

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Mitochondrial copy number and risk of breast cancer: A pilot study

Cited by 141 publications

References 39 publications

Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer

Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer

Mitochondrial DNA Levels in Blood and Tissue Samples from Breast Cancer Patients of Different Stages

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

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