The Association between Telomere Length and Head and Neck Cancer Risk: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Literature Search Strategy
2.1.1. Study Inclusion/Exclusion Criteria
2.1.2. Data Extraction
2.2. Statistical Analysis
2.3. Study Selection
3. Results
3.1. Study Characteristics
3.2. Results of Studies
3.2.1. Meta-Analysis
3.2.2. Subgroup Analysis
3.3. Publication Bias and Sensitivity Analysis
4. Discussion
- (a)
- (b)
- Significant heterogeneity was noted between the included studies. Although we conducted subgroup analyses in order to investigate the source of this heterogeneity, this particular problem may stem from factors that have not been accounted for in our analysis.
- (c)
- In some subgroups, the small number of studies and small sample size limited the ability to derive statistically significant results. Specifically, an important limitation was the lack of data to investigate the relationship of TL with HNC subtypes, with the exception of oral cancers.
- (d)
- While across all studies, the definitions of short and long TL were consistently based on the median telomere length, complete homogeneity was not achieved. In one study [40], the median of all subjects was used as the cutoff point and the necessary data were not provided for the derivation of the results using the median TL of controls as the cutoff, the cutoff used in the other studies.
- (e)
- The studies did not include enough data on TNM/UICC stage, p16 status, or HPV status for a meaningful analysis or subgroup meta-analysis to be performed. Future studies should include such critical data.
- (f)
- The studies included in our meta-analysis had widely heterogeneous approaches to reporting TL measurements (RTL—relative telomere length; age-adjusted relative LTL—leukocyte telomere length; normalized TCRa (NTCR); T/S median; etc.) and some did not include any direct measurements of TL. Therefore, no meaningful analysis could be conducted of the range/median/standard deviation of TL.
- (g)
- Finally, one other potential limitation could be the design of the included studies, as they generally followed a case–control pattern, which has been traditionally associated with an increased risk of bias, especially selection bias [60]. However, certain studies indicate that the results may be similarly robust [61].
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Conflicts of Interest
References
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Author | Year | Country | Cancer Type | Odds Ratio | Sample Size | Cases/ Controls |
---|---|---|---|---|---|---|
Wu [37] | 2003 | USA | Head and Neck | 2.83 | 184 | 92/92 |
Aida [38] | 2010 | Japan | Oral—CIS | 6.5 | 49 | 25/24 |
Liu [39] | 2011 | USA | Head and Neck | 0.97 | 1773 | 885/888 |
Zhang [40] | 2013 | USA | OCC | 1.7 | 523 | 137/335 |
Zhang [40] | 2013 | USA | OPC | 0.8 | 472 | 188/335 |
Bau [41] | 2013 | USA | OSCC | 3.47 | 486 | 92/394 |
Yayun Gu [42] | 2016 | China | Oral Cancer | 1.28 | 1316 | 403/913 |
Yayun Gu [42] | 2016 | China | Other HNC sites | 0.96 | 1020 | 107/913 |
Paiva [43] | 2018 | Brazil | Head and Neck | 2.34 | 359 | 97/262 |
Boscolo-Rizzo [44] | 2020 | Italy | Head and Neck | 1.15 | 27 | 27/27 |
Vaiciulis [45] | 2020 | Lithuania | Laryngeal | 0.79 | 269 | 114/155 |
Author | Year | Study Design | DNA Source | Measurement Method | Mean Age | Gender (Percentage Male) | Adjusted |
---|---|---|---|---|---|---|---|
Wu [37] | 2003 | Retro | Leuko | Southern Blot | 57.6 cases, 57.4 controls | 96% cases, 96% controls | Age, sex, smoking |
Aida [38] | 2010 | Retro | Tumor | Southern Blot | 63.3 cases, 55.4 controls | 75% cases, 74% controls | - |
Liu [39] | 2011 | Retro | Leuko | Real-Time PCR | 56.8 cases, 55.4 controls | 74.8% cases, 74.4% controls | Age, sex, smoking, drinking |
Zhang [40] | 2013 | Retro | Leuko | Real-Time PCR | - | 74.2% cases 1, 80.3% controls | Age, sex, smoking, drinking |
Zhang [40] | 2013 | Retro | Leuko | Real-Time PCR | - | 74.2% cases 1, 80.3% controls | Age, sex, smoking, drinking |
Bau [41] | 2013 | Retro | Leuko | Real-Time PCR | 57.22 cases, 58.30 controls | 59% cases, 57% controls | Age, sex, smoking, drinking |
Yayun Gu [42] | 2016 | Retro | Leuko | Real-Time PCR | 61.29 cases 1, 59.78 controls | 70% cases 1, 74% controls | Age, sex, smoking, drinking |
Yayun Gu [42] | 2016 | Retro | Leuko | Real-Time PCR | 61.29 cases 1, 59.78 controls | 70% cases 1, 74% controls | Age, sex, smoking, drinking |
Paiva [43] | 2018 | Retro-Cohort | Leuko | Rreal-Time PCR | 55 cases | 89% cases | Age, sex |
Boscolo-Rizzo [44] | 2020 | Retro | Tumor | Real-Time PCR | 66 cases | 73% cases | Age, sex, smoking, drinking |
Vaiciulis [45] | 2020 | Retro | Leuko | Real-Time PCR | 62.8 cases, 62.5 controls | 96.3% cases, 96.7% controls | Age, sex |
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Andreikos, D.; Kyrodimos, E.; Kotsinas, A.; Chrysovergis, A.; Papacharalampous, G.X. The Association between Telomere Length and Head and Neck Cancer Risk: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2024, 25, 9000. https://doi.org/10.3390/ijms25169000
Andreikos D, Kyrodimos E, Kotsinas A, Chrysovergis A, Papacharalampous GX. The Association between Telomere Length and Head and Neck Cancer Risk: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences. 2024; 25(16):9000. https://doi.org/10.3390/ijms25169000
Chicago/Turabian StyleAndreikos, Dimitrios, Efthymios Kyrodimos, Athanassios Kotsinas, Aristeidis Chrysovergis, and Georgios X. Papacharalampous. 2024. "The Association between Telomere Length and Head and Neck Cancer Risk: A Systematic Review and Meta-Analysis" International Journal of Molecular Sciences 25, no. 16: 9000. https://doi.org/10.3390/ijms25169000