Causal association between telomere length and female cancers: a two-sample Mendelian randomization study

Area of Science:

• Genetics and Oncology
• Molecular Epidemiology

Background:

• Previous studies suggested an association between telomere length and cancer risk, but the causal relationship was unclear.
• Establishing causality is crucial for identifying potential modifiable risk factors for cancer.

Purpose of the Study:

• To investigate the causal associations between genetically predicted telomere length and the risk of gynecologic cancers (endometrial, ovarian, cervical) and breast cancer.

Main Methods:

• Utilized Mendelian randomization (MR) with genome-wide association study data for telomere length and cancer.
• Employed inverse variance weighted (IVW) as the primary analysis, with weighted median, weighted mode, and MR-Egger for confirmation.
• Assessed heterogeneity, horizontal pleiotropy, and outliers using Cochran's Q-test, MR-Egger regression, and MR-PRESSO, respectively.

Main Results:

• Found significant causal associations between genetically predicted telomere length and increased risk for endometrial cancer (OR=1.29), ovarian cancer (OR=1.27), and breast cancer (OR=1.12).
• Leukocyte telomere length also showed a causal association with endometrial (OR=1.23) and breast cancer (OR=1.12).
• Detected heterogeneity and horizontal pleiotropy in some analyses, particularly for breast cancer, but significance remained after outlier removal.

Conclusions:

• This MR study provides robust evidence for a causal relationship between genetically predicted telomere length and an increased risk of breast, endometrial, and ovarian cancers.
• Highlights the importance of both overall and leukocyte telomere length in cancer risk.
• Findings may guide future research on telomere length as a cancer biomarker and inform the development of targeted interventions and preventive strategies.