Telomere length is associated with increased risk of cutaneous melanoma: a Mendelian randomization study

Author:

Liu Mingjuan123,Lan Yining12,Zhang Hanlin12,Zhang Xinyi45,Wu Mengyin12,Yang Leyan12,Zhou Jia12,Tong Meiyi12,Leng Ling2,Zheng Heyi12,Li Jun12,Mi Xia6

Affiliation:

1. Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

2. State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

3. 4 + 4 M.D. Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

4. Internal Medicine

5. Cellular & Molecular Physiology, Yale School of Medicine, New Haven, Connecticut, USA

6. Department of Dermatology, Strategic Support Force Medical Center, Beijing, China

Abstract

The objective was to investigate the causal association between genetically predicted telomere length (TL) and cutaneous melanoma (CM) risk using Mendelian randomization (MR). This study utilized a two-sample MR and two large genome-wide association studies (GWAS) were used for instrumental variable (IV) selection to select single nucleotide polymorphisms at the genome-wide significance threshold (P < 5E-08) for TL. The IVs were then pruned for linkage disequilibrium and weak instrument bias. Summary statistics from a GWAS meta-analysis of CM were used as the outcome variable. The inverse variance weighted (IVW) method was used as the primary approach for overall causal estimation in MR, with sensitivity analyses performed to assess robustness. All statistical analyses were conducted in R studio. Results The MR analysis using two TL GWAS datasets revealed strong and consistent evidence that long TL is causally associated with an increased risk of CM. The analysis of the Codd et al. dataset found that long TL significantly predicted an elevated risk of CM (IVW OR = 2.411, 95% CI 2.092–2.780, P = 8.05E-34). Similarly, the analysis of the Li et al. dataset yielded consistent positive results across all MR methods, providing further robustness to the causal relationship (IVW OR = 2.324, 95% CI 1.516–3.565, P = 1.11E-04). The study provides evidence for a causal association between TL and CM susceptibility, indicating that longer TL increases the risk of developing CM and providing insight into the unique telomere biology in melanoma pathogenesis. Telomere maintenance pathways may be a potential target for preventing and treating CM.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cancer Research,Dermatology,Oncology

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