Associations of blood mitochondrial DNA copy number with social-demographics and cancer risk: results from the Mano-A-Mano Mexican American Cohort.

David Chang,Jie Shen,Xifeng Wu,Yuanqing Ye,Wong-Ho Chow,Hua Zhao

doi:10.18632/oncotarget.25321

David Chang, Jie Shen

Open Access

https://doi.org/10.18632/oncotarget.25321

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Abstract

The relationship between blood mitochondrial DNA (mtDNA) copy number and subsequent cancer risk has been investigated previously. However, such association has never been examined in Mexican Americans. In the current study, we examined association between social-demographic factors and blood mtDNA copy number, as well as longitudinal relationship between cancer and mtDNA copy number, among 10,802 Mexican Americans in the Mano-A-Mano Mexican American Cohort. Overall, mtDNA copy number was statistically significantly higher among participants who developed cancer during the study period than among cancer-free controls (0.17 vs 0.13, P = 0.007). Among cancer-free control participants, mtDNA copy number significantly differed by social-demographic characteristics. However, there was a large degree of heterogeneity in these effects across the mtDNA copy number distribution. In the longitudinal analysis, we observed that higher mtDNA copy number was positively associated with increased risk of all cancer types (adjusted hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.09–1.17). Participants with mtDNA copy number in the fourth (highest) quartile had a higher risk of all cancer (adjusted HR, 2.12; 95% CI, 1.65–2.73) than did participants in the first (lowest) quartile. In summary, our results in Mexican Americans support an association between increased mtDNA copy number and cancer risk. Our results also suggest that mtDNA copy number may be influenced by social and demographic factors.

Highlights

Mitochondrial DNA is highly vulnerable to oxidative damage because it lacks protection from introns and histones and has less efficient DNA repair mechanisms than nuclear DNA does [1, 2]
We found that among participants born in Mexico, a lower preference for Mexican friends and fewer years of living in the United States were significantly positively correlated with mitochondrial DNA (mtDNA) copy number (P = 0.034 and 0.010, respectively)
We found that elevated mtDNA copy number was associated with an increased risk of all cancers (HR, 1.10; 95% confidence intervals (CIs), 1.05–1.14)

Summary

Introduction

Mitochondrial DNA (mtDNA) is highly vulnerable to oxidative damage because it lacks protection from introns and histones and has less efficient DNA repair mechanisms than nuclear DNA does [1, 2]. Each type of cell or tissue has a fairly constant mtDNA copy number [4]. How mtDNA copy number is maintained remains poorly understood, but the mechanism probably involves mitochondrial function, energy metabolism, and oxidative damage. Molecular epidemiologic studies have examined the relationships between mtDNA copy number in leukocytes or whole blood and the risk of several kinds of cancer [5,6,7,8,9,10,11,12,13,14,15,16].

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