Mitochondrial DNA haplogroup K as a contributor to protection against thyroid cancer in a population from southeast Europe

Cocoș, Relu; Schipor, Sorina; Badiu, Corin; Raicu, Florina

doi:10.1016/j.mito.2017.08.012

Cited by 13 publications

(16 citation statements)

References 58 publications

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“…To our knowledge this report is the first to use survival and cause-specific mortality data in multigeneration matrilineages to identify mitochondrial genetic variants that may slow aging and contribute to longevity by lowering the risk of not just one, but several common causes of death. The previously reported published case-control studies [1][2][3][4][5][6][7][8] attributing protection from several aging-related diseases to haplogroup K, combined with the evidence presented here of haplogroup K2's broad health benefits, based on morbidity and mortality data from multiple multigeneration matrilineages, strongly support the conclusion that haplogroup K, and especially the K2 subclade, contributes to better survival by reducing the risk of dying from not just one, but multiple common diseases. How haplogroup K2 accomplishes this has yet to be determined, and may involve multiple mechanisms.…”

Section: Discussionsupporting

confidence: 79%

“…Mitochondrial haplogroup K has been reported to be increased in frequency in exceptionally long-lived individuals as compared to younger controls, in French [1], Irish [2], and Finnish [3] populations. Other studies, also with a case-control design, have reported an association of haplogroup K with decreased risk of Parkinson Disease [4], Alzheimer Disease in APOE 4 allele carriers [5], pancreatic cancer [6], thyroid cancer [7], and both transient ischemic attack and ischemic stroke [8].…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial genetics of exceptional longevity in multigeneration matrilineages

Kerber

O’Brien

Munger

et al. 2018

Preprint

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Some heritable mitochondrial DNA (mtDNA) sequence variants may slow the rate of aging. The European mitochondrial haplogroup K has previously been reported to be increased in frequency in centenarians and nonagenarians relative to its frequency in younger individuals, by standard case/control study designs. To select for mitochondrial genomes likely to carry beneficial genetic variants, we screened a large genealogical database (the Utah Population Database, UPDB) for mitochondrial lineages in which the frequency of survival past 90 years was significantly higher than in the general population, and also significantly higher than in close non-matrilineal relatives. We ranked 14,900 distinct matrilineages by the strength of their association with longevity. Full sequencing of the mtDNAs from a single individual from each of 53 matrilineages in the top longevity ranks and each of 374 control matrilineages from the general Utah population, followed by analyses of the mtDNA haplogroup frequencies, identified haplogroup K2 as the haplogroup most enriched in frequency by the longevity selection (Odds Ratio = 23.05). We then analyzed overall survival and cause-specific mortality in the several thousand individuals aged 40 years or older whose mtDNA genotypes could be imputed from the 374 fully sequenced control mtDNAs. In these control matrilineages Haplogroup K2 individuals (n=332) enjoyed a significantly lower all-cause mortality risk than the general population (HR=0.81), attributable in part to a significantly lower risk of dying from heart disease (HR=0.50), as well as lower (though not significantly lower) risks of dying from cancer (HR=0.72) and diabetes (HR=0.74). Furthermore, K2 was the only haplogroup in which mortality was reduced for all three of these common causes of death.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Mitochondrial genetics of exceptional longevity in multigeneration matrilineages

Kerber

O’Brien

Munger

et al. 2018

Preprint

View full text Add to dashboard Cite

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“…But, some of the findings are still debatable. Moreover, several studies reported that mtDNA polymorphisms and mitochondrial haplogroups have either predisposing or protective role in various cancer types (Cocos et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…However, thyroid cancer is the most common endocrine malignancy covers 90% of the all endocrine malignancies and it has rapidly increase in global incidence in recent decades (Cocos et al, 2017;Xing, 2013). Beside this, thyroid carcinoma was the third most common malignancy in both gender (12%) in Turkey and the second most common malignancy among Turkish women (12%) according to the 2017 Turkish health ministry official cancer report (http://kanser.gov.tr) .…”

Section: Introductionmentioning

confidence: 99%

“…But only one study in literature includes all mitochondrial genome investigation at PTC samples but the study did not have any benign thyroid tumor samples to demonstrate the influence of the mitochondrial genome in thyroid tumorigenesis (Su et al, 2016). In addition to that, Cocos et al (2017) reported that mtDNA haplogroup K has a protective role for thyroid cancer and suggested that investigating mtDNA haplogroups is a candidate susceptibility marker for the patients with thyroid nodules.…”

Section: Introductionmentioning

confidence: 99%

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The Mitochondrial DNA Control Region might have useful Diagnostic and Prognostic Biomarkers for Thyroid Tumors

Bircan

Gözü

Ulu

et al. 2018

Preprint

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Not all mitochondrial DNAs are made equal and the nucleus knows it

2020

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The oxidative phosphorylation (OXPHOS) system is the only structure in animal cells with components encoded by two genomes, maternally transmitted mitochondrial DNA (mtDNA), and biparentally transmitted nuclear DNA (nDNA). MtDNA‐encoded genes have to physically assemble with their counterparts encoded in the nucleus to build together the functional respiratory complexes. Therefore, structural and functional matching requirements between the protein subunits of these molecular complexes are rigorous. The crosstalk between nDNA and mtDNA needs to overcome some challenges, as the nuclear‐encoded factors have to be imported into the mitochondria in a correct quantity and match the high number of organelles and genomes per mitochondria that encode and synthesize their own components locally. The cell is able to sense the mito‐nuclear match through changes in the activity of the OXPHOS system, modulation of the mitochondrial biogenesis, or reactive oxygen species production. This implies that a complex signaling cascade should optimize OXPHOS performance to the cellular‐specific requirements, which will depend on cell type, environmental conditions, and life stage. Therefore, the mitochondria would function as a cellular metabolic information hub integrating critical information that would feedback the nucleus for it to respond accordingly. Here, we review the current understanding of the complex interaction between mtDNA and nDNA.

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Mitochondrial DNA haplogroup K as a contributor to protection against thyroid cancer in a population from southeast Europe

Cited by 13 publications

References 58 publications

Mitochondrial genetics of exceptional longevity in multigeneration matrilineages

Mitochondrial genetics of exceptional longevity in multigeneration matrilineages

The Mitochondrial DNA Control Region might have useful Diagnostic and Prognostic Biomarkers for Thyroid Tumors

Not all mitochondrial DNAs are made equal and the nucleus knows it

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