Information on over 40 independent breast cancer risk factor-related variables was available for up to 7781 mothers and children with mtDNA haplogroup data in ALSPAC. Risk factor data were obtained from questionnaires, clinic visits and blood measurements. In this study we investigated the association of mtDNA haplogroups of European origin with several breast cancer risk factors in mothers and children of the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort that enrolled over 14,000 pregnant women in the Southwest region of the UK.
However, studies reporting associations between mtDNA haplogroups and breast cancer risk have had a few shortcomings including small sample sizes, failure to account for population stratification and performing inadequate statistical tests. The relationship between mitochondrial DNA (mtDNA) and breast cancer has been frequently examined, particularly in European populations. Further research is required to unravel the role of mtMSI in tumourigenesis. Based on the available published data, mtMSI can act as a vital risk factor and a potential marker for cancer progression. Mutations in the mitochondrial genome are widely believed to have a broad impact across various cancers. In this review, we briefly summarize the knowledge related to possible molecular mechanisms causing mtMSI formation and the available information on mtMSI frequency values in all main solid cancer types. Databases including PubMed, Scopus, and Google Scholar were searched for articles about mtMSI and its link to solid cancer published from 1990 till 2021. This review article aims to highlight the published research work on alterations in mtDNA, with a particular focus on mitochondrial MSI (mtMSI) in various types of solid cancers. Mitochondrial dysregulation can occur as a consequence of molecular alterations in mtDNA, such as point mutations, deletions, inversions, microsatellite instability (MSI), and copy number variations. Thus, failure of their function is crucial for tumourigenesis, tumour cell growth, and metastasis. Mitochondria are essential bioenergetics and biosynthetic machinery found in most eukaryotic organisms. Polymorphic changes are evolutionarily related to haplogroup H of Indo-European and Euro Asiatic origins, however, were found in all non-European sequences with breast cancer.Ĭancer has been broadly considered a genetic disease involving mutations in nuclear DNA and the mitochondrial genome (mtDNA). Also, the variant m.16519T>C (rs3937033) was found in 59% of control sequences and 52% of breast cancer sequences with a significant statistical difference. From mtDNA analysis, two polymorphisms with significative statistical differences were found in D130 in sequences analyzed: m.310del (rs869289246) in 34.6% (27/78) breast cancer cases and 61.7% (21/34) of controls and m.315dup (rs369786048) in 60.2% (47/78) of breast cancer cases and 38.2% (13/34) of controls. Of these 86 complete sequences, 52 belong to patients with a confirmed diagnosis of breast cancer and 34 sequences were obtained from healthy mammary tissue of the same patients used as controls.
We identified 124 mtDNA sequences associated to breast cancer cases of which 86 were complete and 38 partial sequences. The search for complete and partial mtDNA sequences obtained from breast cancer patients and controls was performed in NCBI Genbank database. The purpose of the present work was to explore mitochondrial sequences of clinical cases with breast cancer from different origins and determine the polymorphisms associated. Although alterations in the mitochondrial genome probably play an important role in carcinogenesis, the actual evidence is ambiguous and inconclusive. Breast cancer has an important incidence in the worldwide female population.
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