Mitochondrial DNA Copy Numbers and Lung Cancer: A Systematic Review and Meta-Analysis
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Search Strategy and Data Source
2.2. Eligibility Criteria
2.3. Data Extraction and Quality Assessment
2.4. Statistical Analysis
3. Results
3.1. Study Selection
3.2. Study Characteristics and Quality Assessment
3.3. Meta-Analysis mtDNAcn
3.4. Sensitivity Analysis mtDNAcn
3.5. Publication Bias mtDNAcn
3.6. Dose–Response
4. Discussion
Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Author, Year, Reference | Cohort 1, Location | Study Design | N | Age (M: Mean, Mdn: Median) | Sex (% Male) | Race (% White) | BMI (% or M: Mean, [kg/m2] <25) | Type of LC 2 | Tissue Type | Smoking Status (% Never) | Matched or Adjusted Variables | NOS 3 |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Kennedy GT, 2022 [41] | UPHS, USA | Case–control | Cases: 465 Controls: 378 | Cases: 66 (Mdn) Controls: 58 (Mdn) | Cases: 55.7 Controls: 51.3 | Cases: 81.3 Controls: 63.8 | NSCLC and SCLC | Peripheral blood | Cases: 9.7 Controls: 24.3 | Age, race, gender, tobacco use, and tobacco pack-years | 8 | |
Meng S, 2016 [31] | NHS, USA | Nested case–control | Cases: 285 Controls: 285 | Cases: 59.8 (M) Controls: 59.5 (M) | Cases: 60.9 (%) Controls: 57.3 (%) | LC | Peripheral blood | BMI, physical activity, alcohol consumption. and health eating index score | 9 | |||
HPFS, USA | Nested case–control | Cases: 178 Controls: 178 | Cases: 66.0 (M) Controls: 65.7 (M) | Cases: 42.9 (%) Controls: 31.8 (%) | LC | Peripheral blood | BMI, physical activity, alcohol consumption, and health eating index score | 9 | ||||
Kim C, 2014 [40] | PLCO, USA | Nested case–control | Cases: 426 Controls: 436 | Cases: 64.1 (M) Controls: 63.7 (M) | Cases: 60.8 Controls: 61.2 | Cases: 93.7 Controls: 92.7 | Cases: 26.8 (M) Controls: 27.4 (M) | LC | Peripheral blood | Cases: 10.8 Controls: 45.4 | Age, BMI, pack-years, race, sex, date of enrollment, center (if applicable), and study | 7 |
SWHS, China | Nested case–control | Cases: 221 Controls: 222 | Cases: 59.2 (M) Controls: 59.2 (M) | Cases: 24.6 (M) Controls: 25.0 (M) | LC | Peripheral blood | Cases: 92.3 Controls: 95.0 | Age, BMI, pack-years, race, sex, date of enrollment, center (if applicable), and study | 7 | |||
ATBC, Finland | Nested case–control | Cases: 227 Controls: 227 | Cases: 56.7 (M) Controls: 58.4 (M) | Cases: 25.6 (M) Controls: 26.3 (M) | LC | Peripheral blood | Cases: 0.0 Controls: 0.0 | Age, BMI, pack-years, race, sex, date of enrollment, center (if applicable), and study | 7 | |||
Hosgood HD III, 2010 [39] | ATBC, Finland | Case–control | Cases: 227 Controls: 227 | Cases: 58.7 (M) Controls: 58.4 (M) | Cases: 100 Controls: 100 | Cases: 25.6 (M) Controls: 26.3 (M) | LAUD and LUSC | Peripheral blood | Cases: 0.0 Controls: 0.0 | Age, number of years smoking, and number of cigarettes per day | 7 | |
Bonner MR, 2009 [38] | China (Xuan Wei hospitals) | Case–control | Cases: 113 Controls: 107 | Cases: 54.9 (M) Controls: 54.5 (M) | Cases: 65 Controls: 64 | LC | Sputum | Age, type of current fuel use, sex, pack-years smoking, and lifetime smoky coal use | 6 |
Combined Risk Estimate | Test of Heterogeneity | Publication Bias | |||||
---|---|---|---|---|---|---|---|
N. b | Value (95% CI) | Q | I2 % | p | p (Egger Test) | p (Begg Test) | |
ALL (5art) 1 | 33 | 0.94 (0.49–1.78) | 132.48 | 96.98 | 0.00 | 0.93 | 1.00 |
Excluding Bonner et al. [38] 2 | 31 | 0.81 (0.39–1.67) | 126.82 | 97.63 | 0.00 | 0.75 | 1.00 |
SEX | |||||||
M | 4 | 1.13 (0.65–1.98) | 10.63 | 71.77 | 0.014 | 0.51 | 0.17 |
F | 4 | 1.36 (0.93–2.01) | 4.75 | 36.84 | 0.19 | 0.35 | 0.50 |
Smoking Status | |||||||
CURRENT | 4 | 1.37 (0.90–2.08) | 5.38 | 44.25 | 0.15 | 0.18 | 0.17 |
EVER | 5 | 1.10 (0.81–1.50) | 5.21 | 23.30 | 0.27 | 0.62 | 0.33 |
NEVER | 4 | 1.06 (0.76–1.48) | 0.82 | 0.00 | 0.85 | 0.14 | 0.50 |
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Chiavarini, M.; Dolcini, J.; Firmani, G.; Brennan, K.J.M.; Cardenas, A.; Baccarelli, A.A.; Barbadoro, P. Mitochondrial DNA Copy Numbers and Lung Cancer: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2025, 26, 6610. https://doi.org/10.3390/ijms26146610
Chiavarini M, Dolcini J, Firmani G, Brennan KJM, Cardenas A, Baccarelli AA, Barbadoro P. Mitochondrial DNA Copy Numbers and Lung Cancer: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences. 2025; 26(14):6610. https://doi.org/10.3390/ijms26146610
Chicago/Turabian StyleChiavarini, Manuela, Jacopo Dolcini, Giorgio Firmani, Kasey J. M. Brennan, Andrès Cardenas, Andrea A. Baccarelli, and Pamela Barbadoro. 2025. "Mitochondrial DNA Copy Numbers and Lung Cancer: A Systematic Review and Meta-Analysis" International Journal of Molecular Sciences 26, no. 14: 6610. https://doi.org/10.3390/ijms26146610
APA StyleChiavarini, M., Dolcini, J., Firmani, G., Brennan, K. J. M., Cardenas, A., Baccarelli, A. A., & Barbadoro, P. (2025). Mitochondrial DNA Copy Numbers and Lung Cancer: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences, 26(14), 6610. https://doi.org/10.3390/ijms26146610