scholarly journals Pre-diagnostic leukocyte mitochondrial DNA copy number and colorectal cancer risk

2019 ◽  
Vol 40 (12) ◽  
pp. 1462-1468 ◽  
Author(s):  
Keming Yang ◽  
Xin Li ◽  
Michele R Forman ◽  
Patrick O Monahan ◽  
Bret H Graham ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Quantitative Polymerase Chain Reaction ◽  
Conditional Logistic Regression ◽  
Experimental Studies ◽  
Inverse Association ◽  
Mitochondrial Dna Copy Number ◽  
Increased Risk

Abstract Mitochondrial DNA (mtDNA) is susceptible to oxidative stress and mutation. Few epidemiological studies have assessed the relationship between mtDNA copy number (mtDNAcn) and risk of colorectal cancer (CRC), with inconsistent findings. In this study, we examined the association between pre-diagnostic leukocyte mtDNAcn and CRC risk in a case–control study of 324 female cases and 658 matched controls nested within the Nurses’ Health Study (NHS). Relative mtDNAcn in peripheral blood leukocytes was measured by quantitative polymerase chain reaction-based assay. Conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of interest. Results showed lower log-mtDNAcn was significantly associated with increased risk of CRC, in a dose-dependent relationship (P for trend < 0.0001). Compared to the fourth quartile, multivariable-adjusted OR [95% confidence interval (CI)] was 1.10 (0.69, 1.76) for the third quartile, 1.40 (0.89, 2.19) for the second quartile and 2.19 (1.43, 3.35) for the first quartile. In analysis by anatomic subsite of CRC, we found a significant inverse association for proximal colon cancer [lowest versus highest quartile, multivariable-adjusted OR (95% CI) = 3.31 (1.70, 6.45), P for trend = 0.0003]. Additionally, stratified analysis according to the follow-up time since blood collection showed that the inverse association between mtDNAcn and CRC remained significant among individuals with ≥ 5 years’ follow-up, and marginally significant among those with ≥ 10 years’ follow-up since mtDNAcn testing, suggesting that mtDNAcn may serve as a long-term predictor for risk of CRC. In conclusion, pre-diagnostic leukocyte mtDNAcn was inversely associated with CRC risk. Further basic experimental studies are needed to explore the underlying biological mechanisms linking mtDNAcn to CRC carcinogenesis.

scholarly journals Mitochondrial DNA copy number and incident atrial fibrillation

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Di Zhao ◽  
Traci M. Bartz ◽  
Nona Sotoodehnia ◽  
Wendy S. Post ◽  
Susan R. Heckbert ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Copy Number ◽  
Quantitative Polymerase Chain Reaction ◽  
Snp Array ◽  
Cardiovascular Health Study ◽  
Inverse Association ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Increased Risk ◽  
Mitochondria Dna

Abstract Background Mechanistic studies suggest that mitochondria DNA (mtDNA) dysfunction may be associated with increased risk of atrial fibrillation (AF). The association between mtDNA copy number (mtDNA-CN) and incident AF in the general population, however, remains unknown. Methods We conducted prospective analyses of 19,709 participants from the Atherosclerosis Risk in Communities Study (ARIC), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Cardiovascular Health Study (CHS). mtDNA-CN from the peripheral blood was calculated from probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms (SNP) Array 6.0 in ARIC and MESA and from multiplexed real-time quantitative polymerase chain reaction (qPCR) in CHS. Incident AF cases were identified through electrocardiograms, review of hospital discharge codes, Medicare claims, and death certificates. Results The median follow-up time was 21.4 years in ARIC, 12.9 years in MESA, and 11.0 years in CHS, during which 4021 participants developed incident atrial fibrillation (1761 in ARIC, 790 in MESA, and 1470 in CHS). In fully adjusted models, participants with the lowest quintile of mitochondria DNA copy number had an overall 13% increased risk (95% CI 1 to 27%) of incident atrial fibrillation compared to those with the highest quintile. Dose-response spline analysis also showed an inverse association between mitochondria DNA copy number and hazard for atrial fibrillation for all three cohorts. These associations were consistent across subgroups. Conclusions Mitochondria DNA copy number was inversely associated with the risk of AF independent of traditional cardiovascular risk factors. These findings implicate mitochondria DNA copy number as a novel risk factor for atrial fibrillation. Further research is warranted to understand the underlying mechanisms and to evaluate the role of mitochondria DNA copy number in the management of atrial fibrillation risk.

Abstract 4281: Mitochondrial DNA copy number, urinary isoprostanes and colorectal cancer risk

2016 ◽  
Author(s):  
Bharat Thyagarajan ◽  
Renwei Wang ◽  
Woon-Puay Koh ◽  
Helene Barcelo ◽  
Jennifer Adams-Haduch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mitochondrial Dna ◽  
Cancer Risk ◽  
Copy Number ◽  
Colorectal Cancer Risk ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number

scholarly journals Association between pre-diagnostic leukocyte mitochondrial DNA copy number and survival among colorectal cancer patients

2020 ◽  
Vol 68 ◽  
pp. 101778
Author(s):  
Keming Yang ◽  
Michele R. Forman ◽  
Brett H. Graham ◽  
Patrick O. Monahan ◽  
Edward L. Giovannucci ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mitochondrial Dna ◽  
Cancer Patients ◽  
Copy Number ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Colorectal Cancer Patients

scholarly journals Mitochondrial DNA copy number and diabetes: the Atherosclerosis Risk in Communities (ARIC) study

2020 ◽  
Vol 8 (1) ◽  
pp. e001204
Author(s):  
Bailey DeBarmore ◽  
Ryan J Longchamps ◽  
Yiyi Zhang ◽  
Rita R Kalyani ◽  
Eliseo Guallar ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Copy Number ◽  
Buffy Coat ◽  
Incident Diabetes ◽  
Atherosclerosis Risk In Communities ◽  
Mitochondrial Dna Copy Number ◽  
Atherosclerosis Risk ◽  
Aric Study

IntroductionMitochondrial DNA copy number (mtDNA-CN) is a measure of mitochondrial dysfunction and is associated with diabetes in experimental models. To explore the temporality of mitochondrial dysfunction and diabetes, we estimated the prevalent and incident association of mtDNA-CN and diabetes.Research design and methodsWe assessed the associations of mtDNA-CN measured from buffy coat with prevalent and incident diabetes, stratified by race, in 8954 white and 2444 black participants in the Atherosclerosis Risk in Communities (ARIC) study, an observational cohort study. Follow-up for incident analyses was complete through visit 6, 2016.ResultsMean age at mtDNA-CN measurement was 57 years and 59% were female. Prevalence of diabetes at time of mtDNA-CN measurement was higher in blacks (563/2444, 23%) than whites (855/8954, 10%). The fully adjusted odds of prevalent diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.05 (95% CI 0.74 to 1.49) among black and 1.49 (95% CI 1.20 to 1.85) among white participants. Over a median follow-up time of 19 years (Q1, Q3: 11, 24 years), we observed 617 incident diabetes cases among 1744 black and 2121 cases among 7713 white participants free of diabetes at baseline. The fully adjusted hazard of incident diabetes for the 10th vs 90th percentile of mtDNA-CN was 1.07 (95% CI 0.84 to 1.38) among black and 0.97 (95% CI 0.86 to 1.10) among white participants.ConclusionsLower mtDNA-CN in buffy coat was associated with prevalent diabetes in white but not black ARIC participants. Lower mtDNA-CN was not associated with incident diabetes over 20 years of follow-up in whites or blacks.

scholarly journals Serum IGFBP-2 and Risk of Atypical Hyperplasia of the Breast

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Chelsea Catsburg ◽  
Marc J. Gunter ◽  
Lesley Tinker ◽  
Rowan T. Chlebowski ◽  
Michael Pollak ◽  
...  
Keyword(s):  
Conditional Logistic Regression ◽  
Atypical Hyperplasia ◽  
Mammary Tissue ◽  
Inverse Association ◽  
Logistic Regression Models ◽  
Increased Risk ◽  
Nested Case Control ◽  
Nonsignificant Decrease ◽  
Control Study

Atypical hyperplasia of the breast (AH) is associated with increased risk of subsequent invasive breast cancer, yet little is known about the etiology of AH. Insulin-like growth factor binding protein 2 (IGFBP-2) may contribute to the development of AH due to its proliferative effects on mammary tissue. We conducted a nested case-control study of postmenopausal women enrolled in Women’s Health Initiative-Clinical Trial. Cases were 275 women who developed incident AH during follow-up, individually (1 : 1) matched to controls. Levels of IGFBP-2 were determined from fasting serum collected at baseline. Multivariable conditional logistic regression models were used to estimate odds ratios for the association of IGFBP-2 with risk of AH. Serum IGFBP-2 was associated with a nonsignificant decrease in risk for AH, when comparing the highest quartile to lowest quartile (OR = 0.65; 95% CI = 0.32–1.31). This decrease in risk was most evident when analyses were restricted to nondiabetic, nonusers of hormone therapy (OR = 0.33, 95% CI = 0.13–0.86,ptrend= 0.06) and nondiabetic women who were overweight or obese (OR = 0.43, 95% CI = 0.18–1.03,ptrend= 0.05). Results from this study provide some support for an inverse association between serum IGFBP2 levels and risk of AH, particularly in nondiabetic women who are overweight or obese. Further studies are required to confirm these results.

scholarly journals Mitochondrial DNA copy number in colorectal cancer: between tissue comparisons, clinicopathological characteristics and survival

2015 ◽  
pp. bgv151 ◽  
Author(s):  
Frits H.M. van Osch ◽  
An M. Voets ◽  
Leo J. Schouten ◽  
Ralph W.H. Gottschalk ◽  
Colinda C.J.M. Simons ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Clinicopathological Characteristics ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number

scholarly journals Mitochondrial DNA Copy Number in Peripheral Blood Is Independently Associated with Visceral Fat Accumulation in Healthy Young Adults

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jee-Yon Lee ◽  
Duk-Chul Lee ◽  
Jee-Aee Im ◽  
Ji-Won Lee
Keyword(s):  
Young Adults ◽  
Mitochondrial Dna ◽  
Visceral Fat ◽  
Copy Number ◽  
Visceral Obesity ◽  
Mtdna Copy Number ◽  
Metabolic Disturbances ◽  
Visceral Fat Area ◽  
Mitochondrial Dna Copy Number ◽  
Increased Risk

Aims. Visceral obesity is associated with an increased risk of cardiometabolic diseases and it is important to identify the underlying mechanisms. There is growing evidence that mitochondrial dysfunction is associated with metabolic disturbances related to visceral obesity. In addition, maintaining mitochondrial DNA (mtDNA) copy number is important for preserving mitochondrial function. Therefore, we investigated the relationship between mtDNA copy number and visceral fat in healthy young adults.Methods. A total of 94 healthy young subjects were studied. Biomarkers of metabolic risk factors were assessed along with body composition by computed tomography. mtDNA copy number was measured in peripheral leukocytes using real-time polymerase chain reaction (PCR) methods.Results. The mtDNA copy number correlated with BMI (r=-0.22,P=0.04), waist circumference (r=-0.23,P=0.03), visceral fat area (r=-0.28,P=-0.01), HDL-cholesterol levels (r=0.25,P=0.02), and hs-CRP (r=0.32,P=0.02) after adjusting for age and sex. Both stepwise and nonstepwise multiple regression analyses confirmed that visceral fat area was independently associated with mtDNA copy number (β=-0.33,P<0.01,β=0.32, andP=0.03, resp.).Conclusions. An independent association between mtDNA content and visceral adiposity was identified. These data suggest that mtDNA copy number is a potential predictive marker for metabolic disturbances. Further studies are required to understand the causality and clinical significance of our findings.

scholarly journals Association of mitochondrial DNA copy number with prevalent and incident type 2 diabetes in women: A population-based follow-up study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashfaque A. Memon ◽  
Jan Sundquist ◽  
Anna Hedelius ◽  
Karolina Palmér ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Smoking Status ◽  
Population Based ◽  
Dna Copy Number ◽  
Follow Up Study ◽  
Mitochondrial Dna Copy Number

AbstractMitochondrial dysfunction is an important factor of the aging process and may play a key role in various diseases. Mitochondrial DNA copy number (mtDNA-CN) is an indirect measure of mitochondrial dysfunction and is associated with type 2 diabetes mellitus (T2DM); however, whether mtDNA-CN can predict the risk of developing T2DM is not well-known. We quantified absolute mtDNA-CN in both prevalent and incident T2DM by well-optimized droplet digital PCR (ddPCR) method in a population-based follow-up study of middle aged (50–59 years) Swedish women (n = 2387). The median follow-up period was 17 years. Compared to those who were free of T2DM, mtDNA-CN was significantly lower in both prevalent T2DM and in women who developed T2DM during the follow-up period. Mitochondrial DNA-copy number was also associated with glucose intolerance, systolic blood pressure, smoking status and education. In multivariable Cox regression analysis, lower baseline mtDNA-CN was prospectively associated with a higher risk of T2DM, independent of age, BMI, education, smoking status and physical activity. Moreover, interaction term analysis showed that smoking increased the effect of low mtDNA-CN at baseline on the risk of incident T2DM. Mitochondrial DNA-copy number may be a risk factor of T2DM in women. The clinical usefulness of mtDNA-CN to predict the future risk of T2DM warrants further investigation.

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