A mitochondrial DNA variant 10398G&gt;A in breast cancer among South Indians: An original study with meta-analysis

Francis, Amirtharaj; Singh, Pooja; Rajender, Singh; Govindaraj, Periyasamy; Tipirisetti, Nageswara Rao; Surekha, D; Rao, Digumarthi Raghunatha; Rao, Lakshmi; Ramachandra, Lingadakai; Satti, Vishnupriya; Ramalingam, K.; Satyamoorthy, Kapaettu; Thangaraj, Kumarasamy

doi:10.1016/j.mito.2013.08.004

Cited by 17 publications

(25 citation statements)

References 52 publications

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“…It seems that both 10398A and 10398G are not deleterious alleles for breast cancer risk in Han Chinese women. A recent meta‐analysis, which did not include any research into Chinese populations, showed a similar negative overall correlation between this polymorphism and breast cancer risk …”

Section: Discussionmentioning

confidence: 84%

“…A recent meta-analysis, which did not include any research into Chinese populations, showed a similar negative overall correlation between this polymorphism and breast cancer risk. (38) It was hypothesized that levels of mtDNA copy number might be affected by the intracellular and extracellular environment. Previous studies about tissues of various cancers, including breast cancer, suggested that decreased mtDNA copy number was associated with the occurrence of somatic point mutations located close to the replication origins of the heavystrand and ⁄ or those at the D310 homopolymeric C-stretch (Ctract) in the D-loop region.…”

Section: Discussionmentioning

confidence: 99%

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Peripheral blood mitochondrial DNA content, A10398G polymorphism, and risk of breast cancer in a Han Chinese population

Jiang

Zhao

Xu³

et al. 2014

Cancer Science

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It has been reported that quantitative alterations and sequence variations of mtDNA are associated with the onset and progression of particular types of tumor. However, the relationship between mtDNA content, certain mtDNA polymorphisms in peripheral blood leukocytes and breast cancer risk remain obscure. This study was undertaken to investigate whether mtDNA content and the A10398G polymorphism in peripheral blood leukocytes could be used as risk predictors for breast cancer in Han Chinese women. Blood samples were obtained from a total of 506 breast cancer patients and 520 matched healthy controls. The mtDNA content was measured by using quantitative real-time PCR assay; A10398G polymorphism was determined by PCR-RFLP assay. There was no statistically significant difference between cases and controls in terms of peripheral blood mtDNA content or A10398G polymorphism. However, further analysis suggested that the risk of breast cancer was associated with decreased mtDNA content in premenopausal women (P = 0.001; odds ratio = 0.54; 95% confidence interval, 0.38–0.77), with increased mtDNA content in postmenopausal women (P = 0.027; odds ratio = 1.49; 95% confidence interval, 1.05–2.11). In addition, the associations between mtDNA content and several clinicopathological parameters of cases such as age, menopausal status, and number of pregnancies and live births were observed. This case–control study indicated that the peripheral blood mtDNA content might be a potential biomarker to evaluate the risk of breast cancer for selected Chinese women.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Peripheral blood mitochondrial DNA content, A10398G polymorphism, and risk of breast cancer in a Han Chinese population

Jiang

Zhao

Xu³

et al. 2014

Cancer Science

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“…In an Indian population with haplogroup N, an association was found between m.10398A and breast and esophageal cancer [119]. However, in another study by Francis et al within an Indian population no correlation was found between the m.10398A polymorphism and increased breast cancer risk [120]. In a study performed by Mosquera-Miguel et al also no association was found for this variation in a Spanish population [121].…”

Section: Germline Mtdna Mutations Associated With Cancermentioning

confidence: 90%

“…Multiple studies only looked at certain SNPs [66,115,118,120,121,[123][124][125] and others performed complete mtDNA sequencing to pick up variants [65], which give more inside in the different types of variations. It should be taken into account that also individual non-synonymous polymorphisms are able to influence mitochondrial function and that restricting analysis to haplogroup variation does not cover the load of mtDNA variation.…”

Section: Germline Mtdna Mutations Associated With Cancermentioning

confidence: 99%

How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models

Gisbergen

Voets

Starmans

et al. 2015

Mutation Research/Reviews in Mutation Research

162

151

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Several mutations in nuclear genes encoding for mitochondrial components have been associated with an increased cancer risk or are even causative, e.g. succinate dehydrogenase (SDHB, SDHC and SDHD genes) and iso-citrate dehydrogenase (IDH1 and IDH2 genes). Recently, studies have suggested an eminent role for mitochondrial DNA (mtDNA) mutations in the development of a wide variety of cancers. Various studies associated mtDNA abnormalities, including mutations, deletions, inversions and copy number alterations, with mitochondrial dysfunction. This might, explain the hampered cellular bioenergetics in many cancer cell types. Germline (e.g. m.10398A>G; m.6253T>C) and somatic mtDNA mutations as well as differences in mtDNA copy number seem to be associated with cancer risk. It seems that mtDNA can contribute as driver or as complementary gene mutation according to the multiple-hit model. This can enhance the mutagenic/clonogenic potential of the cell as observed for m.8993T>G or influences the metastatic potential in later stages of cancer progression. Alternatively, other mtDNA variations will be innocent passenger mutations in a tumor and therefore do not contribute to the tumorigenic or metastatic potential. In this review, we discuss how reported mtDNA variations interfere with cancer treatment and what implications this has on current successful pharmaceutical interventions. Mutations in MT-ND4 and mtDNA depletion have been reported to be involved in cisplatin resistance. Pharmaceutical impairment of OXPHOS by metformin can increase the efficiency of radiotherapy. To study mitochondrial dysfunction in cancer, different cellular models (like ρ(0) cells or cybrids), in vivo murine models (xenografts and specific mtDNA mouse models in combination with a spontaneous cancer mouse model) and small animal models (e.g. Danio rerio) could be potentially interesting to use. For future research, we foresee that unraveling mtDNA variations can contribute to personalized therapy for specific cancer types and improve the outcome of the disease.

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“…Similarly, 10398A allele is also associated with breast and esophageal cancer in North Indian women [22]. However, other studies demonstrate that mtDNA G10398A polymorphism do not associate with breast cancer in African-American or South Indian women [116, 117]. In contrast, the 10398G polymorphism of ND3 has been shown to increase the risk of breast cancer in European American, Polish, and Malay populations [22, 78, 96, 118, 119].…”

Section: Germline Mtdna Mutations and Breast Tumorigenesismentioning

confidence: 99%

Mitochondrial DNA mutations and breast tumorigenesis

Yadav

Chandra

2013

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Breast cancer is a heterogeneous disease and genetic factors play an important role in its genesis. Although mutations in tumor suppressors and oncogenes encoded by the nuclear genome are known to play a critical role in breast tumorigenesis, the contribution of the mitochondrial genome to this process is unclear. Like the nuclear genome, the mitochondrial genome also encodes proteins critical for mitochondria functions such as oxidative phosphorylation (OXPHOS), which is known to be defective in cancer including breast cancer. Due to limited repair mechanisms compared to that for nuclear DNA (nDNA), mitochondrial DNA (mtDNA) is more susceptible to mutations. Thus changes in mitochondrial genes could also contribute to the development of breast cancer. In this review we discuss mtDNA mutations that affect OXPHOS. Continuous acquisition of mtDNA mutations and selection of advantageous mutations ultimately leads to generation of cells that propagate uncontrollably to form tumors. Since irreversible damage to OXPHOS leads to a shift in energy metabolism towards enhanced aerobic glycolysis in most cancers, mutations in mtDNA represent an early event during breast tumorigenesis, and thus may serve as potential biomarkers for early detection and prognosis of breast cancer. Because mtDNA mutations lead to defective OXPHOS, development of agents that target OXPHOS will provide specificity for preventative and therapeutic agents against breast cancer with minimal toxicity.

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A mitochondrial DNA variant 10398G>A in breast cancer among South Indians: An original study with meta-analysis

Cited by 17 publications

References 52 publications

Peripheral blood mitochondrial DNA content, A10398G polymorphism, and risk of breast cancer in a Han Chinese population

Peripheral blood mitochondrial DNA content, A10398G polymorphism, and risk of breast cancer in a Han Chinese population

How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models

Mitochondrial DNA mutations and breast tumorigenesis

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