Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta-analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health-related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR-Egger, weighted median, MR-PRESSO, and multivariate MR. Meta-analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non-GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta-analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length.

Background. The use of adjuvant radiotherapy (RT) for well-differentiated liposarcoma (WD-LPS) patients with positive surgical margins is unclear. We aim to compare the overall survival (OS) and cancer-specific survival (CSS) of well-differentiated liposarcoma patients with positive surgical margins in an RT group and non-RT group. Methods. WD-LPS patients with positive margins from 2000 to 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and divided into two groups: RT group and non-RT group. Kaplan–Meier survival analysis with the log-rank test was performed to evaluate the difference of overall survival (OS) and cancer-specific survival (CSS) between groups. Univariate and multivariate Cox proportional hazard analyses were performed to identify important prognostic factors of OS and CSS. Analyses were adjusted using propensity-score matching. Results. We identified 2549 patients: 377 (14.79%) with RT and 2172 (85.21%) without RT. The median age was 61 years, and the median follow-up time was 68 months. The log-rank test revealed that there was no significant difference of CSS between RT and non-RT groups ( P = 0.81 ). The 5-year and 10-year CSS were comparable ( P = 0.418 and P = 0.987 ). Additionally, the use of RT was neither an independent prognostic factor for OS nor CSS. Age, sex, tumor site, the use of chemotherapy were independent prognostic factors for OS after propensity score matching, while race and the tumor site were independent prognostic factors for CSS. Conclusion. Adjuvant RT had no significant improvement on OS and CSS of WD-LPS patients with positive surgical margins.