Abstract
Mitochondria show the special role in cellular bioenergy and many essential physiological activities. Previous researches have suggested that variations of mitochondrial DNA copy number contribute to development of different types of carcinomas. However, the relationship of mtDNA copy number in peripheral blood leukocytes (PBLs) with the risk of head and neck squamous cell carcinoma (HNSCC) is still inconclusive. We investigated the association of mtDNA with HNSCC risk through a case–control study including 570 HNSCC cases and 597 cancer‐free controls. mtDNA copy number in PBLs was measured by real‐time qPCR. Logistic regression was performed to estimate the association between the mtDNA copy number in PBLs and HNSCC risk. A U‐shaped relation between the mtDNA copy number and HNSCC risk was found. Compared with those in the second quartile group, the adjusted odds ratios (ORs) and 95% confidence interval (CI) for those in the first and the forth quartile groups were 1.95 (1.37–2.76) and 2.16 (1.53–3.04), respectively. Using restricted cubic spline analysis, we confirmed such a significant U‐shaped relation. Furthermore, the U‐shaped association remained significant in different subgroups stratified by age, gender, tobacco smoking, and alcohol consumption. Both extremely low and high mtDNA copy numbers had significant associations with the increased HNSCC risk.
Highlights
Mitochondria are complex and dynamic organelle [1] containing 2–10 mitochondrial DNA molecules [2], which explore a significant role in the function and longevity of the vast majority of eukaryotic cell and organisms [1]
Higher mitochondrial DNA (mtDNA) copy number was related to the elevated risk of renal cell carcinoma [16], but lower mtDNA copy number increased the risk of endometrial cancer and melanoma [17, 18]
We conducted a case–control study to evaluate the relationship between mtDNA copy number and head and neck squamous cell carcinoma (HNSCC) risk and found that both extremely low and high mtDNA copy number had significant associations with the increased risk of HNSCC
Summary
Mitochondria are complex and dynamic organelle [1] containing 2–10 mitochondrial DNA (mtDNA) molecules [2], which explore a significant role in the function and longevity of the vast majority of eukaryotic cell and organisms [1]. Head and neck cancer mainly includes squamous cell carcinomas situating in oral cavity, oropharynx, hypopharynx, and larynx [19]. It ranks sixth among all cancers and accounts for about 4% new cases and 5% deaths of all malignancies around the world [20]. Some reports and studies have focused on the role of mtDNA copy number in HNSCC development [22,23,24,25,26,27]; the sample sizes were relatively small (total number of cases and controls: 155–500) and their results were inconsistent [22,23,24,25,26,27]. We examined the relationship between mtDNA copy number and HNSCC risk in a relatively larger case–control study (570 HNSCC cases and 597 controls) in China
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