Causal effects of telomere length on ovarian tumor risk: Insights from genetic evidence

BACKGROUND: Currently, contradictions remain regarding the causal relationship between telomere length (TL) and ovarian tumors (OT). To elucidate the potential causal relationship, we conducted a two-sample bidirectional Mendelian randomization (MR) study. METHOD: All the data were from European populations and obtained from the Genome-Wide Association Study, the FinnGen study, and the Ovarian Cancer Association Consortium. We used inverse variance weighting (IVW) as the primary method, supplemented by other five methods to calculate odds ratios (OR) and 95 % confidence intervals (95 % CI) and checked for pleiotropy. Cochran's Q was used to detect heterogeneity. RESULTS: The IVW method supported TL as a risk factor for malignant (OR = 1.273, 95 % CI = 1.012-1.602) and benign ovarian tumors (BOTs) (OR = 1.337, 95 % CI = 1.093-1.637). Besides, ovarian cancer subtypes evaluated the strong causal relationship between TL and low malignant potential serous ovarian cancer (LMSOC) by applying the IVW method after Bonferroni correction. There was suggestive evidence for low malignant potential mucinous ovarian cancer, invasive mucinous ovarian cancer, and low-grade serous ovarian cancer. No causal relationships were found for other ovarian cancer subtypes. CONCLUSION: Our MR study provides strong genetic evidence that longer telomere length increases risk of specific ovarian tumor subtypes-most robustly for benign ovarian tumors (BOTs) and low malignant potential serous ovarian cancer (LMSOC). For other subtypes, observed associations were suggestive but inconclusive after multiplicity correction, highlighting the etiological heterogeneity of ovarian tumors To optimize treatment regimens and preventive measures for OT, we will continue to thoroughly investigate the potential mechanism of action of these associations in future studies.