Abstract
Background Epidemiological investigations implied that inter-individual variations of mitochondrial DNA copy number (mtDNAcn) could trigger predisposition to multiple cancers, but evidence regarding gastrointestinal cancers (GICs) was still uncertain.
Methods We conducted a case-cohort study within the prospective Dongfeng-Tongji cohort, including incident cases of colorectal cancer (CRC, n=278), gastric cancer (GC, n=138), and esophageal cancer (EC, n=72) as well as a random subcohort (n=1173), who were followed up from baseline to the end of 2018. Baseline blood mtDNAcn was determined with quantitative PCR assay, and associations of mtDNAcn with the GICs risks were estimated by using weighted Cox proportional hazards models.
Results Significant U-shaped associations were observed between mtDNAcn and risks of CRC, GC, EC, and total GICs. Compared to subjects within the 2nd quartile (Q2) mtDNAcn subgroup, those within the 1st (Q1), 3rd (Q3) and 4th (Q4) quartile subgroups showed increased risks of CRC [HR(95%CI)=2.27(1.47-3.52), 1.65(1.04-2.62), and 2.81(1.85-4.28), respectively] and total GICs [HR(95%CI)=1.84(1.30-2.60), 1.47(1.03-2.10), and 2.51(1.82-3.47), respectively], and those within Q4 subgroup present elevated GC and EC risks [HR(95%CI)=2.16(1.31-3.54) and 2.38(1.13-5.02), respectively]. Similar associations of mtDNAcn with CRC and total GICs risks remained in stratified analyzes by age, gender, and smoking status. Notably, there were joint effects of age and smoking status with mtDNAcn on CRC and total GICs risks.
Conclusions This prospectively case-cohort study showed U-shaped associations between mtDNAcn and incident risks of GICs, but further researches are needed to confirm these results and uncover underlying biological mechanisms.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This study was supported by the funds from the National Key Research and Development Program of China (Grant No.2018YFC2000203) and National Youth Top Talent Support Program to H.G., as well as supported by the Fundamental Research Funds for the Central Universities, HUST: 2020JYCXJJ020.
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The study protocol was ethically approved by the Ethics and Human Subject Committee of Tongji Medical College, Huazhong University of Science and Technology. Informed consent was obtained from all participants.
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Footnotes
Declaration of competing financial interest: The authors declare no competing financial interest.
Data Availability
Data sharing is not applicable to this paper as the datasets generated needed to be confidential.