The association between telomere length and malignant lymphoma: A Mendelian randomization Study

Abstract

Abstract There is a growing body of evidence suggesting a close association between telomere length (TL) and the development and progression of cancer. Therefore, the purpose of our study is to explore the potential causal relationship between telomere length and malignant lymphoma (ML). Summary-level data for telomere length and malignant lymphoma data have been retrieved through genome-wide association study (GWAS). Subsequently, A two-sample Mendelian randomization analysis was conducted to assess the causal relationship between TL and ML. The causal effect estimation is achieved primarily by utilizing inverse variance weighting (IVW), with other Mendelian randomization (MR) analysis methods being employed as supplements. A total of 140 single nucleotide polymorphisms (SNPs) with genome-wide significance were identified and employed as instrumental variables (IV) for TL. Based on MR analyses, TL was positively associates with ML,with an odds ratio (OR) of 1.407, 95% confidence interval (CI): 1.126-1.758 and p value of 0.003 as indicated by the IVW method. This result were validated by other complementary MR methods as well. No significant horizontal pleiotropy was observed according to the MR-Egger regression (intercept = -0.006, p = 0.153). The sensitivity analysis confirmed the reliability of the results. This study provides the first evidence of a causal relationship between TL and ML, demonstrating that longer telomere length is associated with a higher risk of malignant lymphoma.