Association of Mitochondrial DNA Copy Number and Telomere Length with Prevalent and Incident Cancer and Cancer Mortality in Women: A Prospective Swedish Population-Based Study

Abstract

Changes in mitochondrial DNA copy number (mtDNA-CN) and telomere length have, separately, been proposed as risk factors for various cancer types. However, those results are conflicting. Here, mtDNA-CN and relative telomere length were measured in 3225 middle-aged women included in a large population-based prospective cohort. The baseline mtDNA-CN in patients with prevalent breast cancer was significantly higher (12.39 copies/µL) than cancer-free individuals. During an average of 15.2 years of follow-up, 520 patients were diagnosed with cancer. Lower mtDNA-CN was associated with decreased risk of genital organ cancer (hazard ratio (HR), 0.84), and shorter telomere length was associated with increased risk of urinary system cancer (HR, 1.79). Furthermore, mtDNA-CN was inversely associated with all-cause (HR, 1.20) and cancer-specific mortality (HR, 1.21) when considering all cancer types. Surprisingly, shorter telomere length was associated with decreased risk of cancer-specific mortality when considering all cancer types (HR, 0.85). Finally, lower mtDNA-CN and shorter telomere length were associated with increased risk of both all-cause and cancer-specific mortality in genital organ cancer patients. In this study population, we found that mtDNA-CN and telomere length were significantly associated with prevalent and incident cancer and cancer mortality. However, these associations were cancer type specific and need further investigation.

Baseline mitochondrial DNA copy number and heart failure incidence and its role in overall and heart failure mortality in middle-aged women

“…However, it is important to note that mtDNA-CN depends on cell-type and the disease in question ( 10 ). For example, using whole blood, we and others have shown that mtDNA-CN is decreased in people with CVDs ( 11 ) whereas both low and high mtDNA-CN have been shown in people with T2D ( 12 , 13 ) and cancer ( 14 ), probably depending on study design, severity of the disease and methods used.…”

Mitochondrial DNA copy number and cancer risks: A comprehensive Mendelian randomization analysis

“…Li et al 17 conducted a prospective Swedish population-based study and found that mtDNA-CN was inversely associated with allcause and cancer-specific mortality when analyzing all cancer types.…”

“…Similar findings were reported for gastric, kidney, lung, prostate, pancreatic, thyroid, and breast cancers. Several studies demonstrated an association between high mtDNA content and disease severity, 14–25 whereas other studies reported an inverse association 26–28 . A large meta‐analysis conducted by Giaccherini et al 28 revealed significant associations between mtDNA‐CN and specific cancer types.…”

Assessment of Telomere Length and Mitochondrial DNA Copy Number in Granulosa Cells as Predictors of Aneuploidy Rate in Young Patients

“…Telomeres are repetitive DNA-protein complexes containing TTAGGG repeats, and the length of telomeres shortens accompanying with cell division [ 40 ]. Telomere attrition would affect the mitochondrial function and biogenesis through pathways involving the peroxisome proliferator-activated receptor gamma co-activator 1α/β (PGC-1α/β), p53, and mTORC1 [ 41 , 42 ]. Telomere shortening may activate the DNA damage response (DDR) which in turn causes the increase of mitochondrial content [ 43 ].…”