Telomere length and skin cancer risk: A systematic review and meta-analysis of melanoma, basal cell carcinoma and squamous cell carcinoma

Abstract

Skin cancer is one of the most prevalent types of cancer worldwide, with its global incidence rising despite prevention efforts. Telomere length (TL) has emerged as a potential biomarker for cancer risk; however, its relationship with skin cancer risk remains incompletely understood. To explore the association between TL and the risk of melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), a systematic review and meta-analysis was conducted. Longer TL was significantly associated with an increased risk in melanoma (pooled odds ratio: 0.51; 95% confidence interval: 0.38-0.69; P<0.0001). A significant association between longer TL and increased melanoma risk was identified in both familial melanoma and the general population. Subgroup analyses revealed consistent associations across sex, population source and adjustments for confounding factors. Geographic stratification indicated stronger associations in studies conducted in the USA compared with those from European populations. A meta-analysis of BCC and SCC studies did not achieve statistical significance, although qualitative synthesis suggested a potential association between shortened TL and increased risk. The significant association of longer TL and increased melanoma risk diverges from the conventional hypothesis that telomere shortening elevates cancer risk, highlighting a cancer-type specific telomeric relationship. The inconclusive findings for BCC and SCC underscore the necessity for further detailed investigation. Large-scale prospective studies with standardized methodologies are imperative to validate these findings and explore the underlying mechanisms. The present findings suggested that TL could potentially serve as a valuable biomarker for melanoma risk stratification in dermatologic oncology.

Keywords: basal cell carcinoma; biomarker; cancer; melanoma; skin cancer; squamous cell carcinoma; telomere biology; telomere length.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of the systematic review and meta-analysis.

Figure 2.

Forest plot of a meta-analysis depicting the association between telomere length and melanoma risk using a random-effects model. CI, confidence interval; FM, familial melanoma; SM, sporadic melanoma; NHS, Nurses' Health Study; WHI-OS, Women's Health Initiative Observational Study; HPFS, Health Professionals Follow-up Study.

Figure 3.

Forest plot of a meta-analysis depicting the relationship between telomere length and basal cell carcinoma risk based on a random-effects model. CI, confidence interval; NHS, Nurses' Health Study.

Figure 4.

Forest plot of a meta-analysis depicting the association between telomere length and squamous cell carcinoma risk using a random-effects model. CI, confidence interval; HPFS, Health Professionals Follow-up Study.

Figure 5.

Forest plot of a subgroup analysis depicting the association between telomere length and melanoma risk stratified by geographic location (USA vs. Europe) using a random-effects model. CI, confidence interval; FM, familial melanoma; SM, sporadic melanoma; WHI-OS, Women's Health Initiative Observational Study; HPFS, Health Professionals Follow-up Study.

Figure 6.

Forest plot of a subgroup analysis depicting the association between telomere length and melanoma risk stratified by sex (female-only vs. mixed-sex studies) using a random-effects model. CI, confidence interval; FM, familial melanoma; SM, sporadic melanoma; WHI-OS, Women's Health Initiative Observational Study.

Figure 7.

Forest plot of a subgroup analysis depicting the association between telomere length and melanoma risk stratified by genetic predisposition (familial vs. general population studies) using a random-effects model. CI, confidence interval; FM, familial melanoma; SM, sporadic melanoma; WHI-OS, Women's Health Initiative Observational Study; HPFS, Health Professionals Follow-up Study.

Figure 8.

Forest plot of a subgroup analysis depicting the association between telomere length and melanoma risk stratified by population source (hospital-based vs. population-based studies) using a random-effects model. CI, confidence interval; FM, familial melanoma; SM, sporadic melanoma; WHI-OS, Women's Health Initiative Observational Study; HPFS, Health Professionals Follow-up Study.

Figure 9.

Forest plot of a subgroup analysis depicting the association between telomere length and melanoma risk stratified by adjustment level (melanoma-specific vs. general adjustments) using a random-effects model. CI, confidence interval; FM, familial melanoma; SM, sporadic melanoma; WHI-OS, Women's Health Initiative Observational Study; HPFS, Health Professionals Follow-up Study.

Figure 10.

Funnel plot of studies included in the melanoma meta-analysis.

Figure 11.

Leave-one-out sensitivity analysis for the association between telomere length and melanoma risk. OR, odds ratio; CI, confidence interval; FM, familial melanoma; SM, sporadic melanoma; NHS, Nurses' Health Study; WHI-OS, Women's Health Initiative Observational Study; HPFS, Health Professionals Follow-up Study.

Figure 12.

Telomere dynamics in melanoma tumourigenesis. Schematic diagram illustrating a potential mechanism underlying the protective effect of shorter telomeres in melanoma. Exposure to ultraviolet radiation induces mutations in melanocytes, particularly in individuals with familial melanoma or those harbouring predisposing mutations. Mutated melanocytes with shorter telomeres have a restricted proliferative capacity, limiting their potential for malignancy. Mutated melanocytes with long telomeres exhibit an increased proliferative lifespan, allowing for the accumulation of additional mutations, which may be corollary to melanoma development. Elements of the figure were created using components from Servier Medical Art. Servier Medical Art by Servier is licensed under Creative Commons Attribution 4.0 (https://creativecommons.org/licenses/by/4.0/).