The number of lifetime sexual partners may not be associated with cervical cancer: A Mendelian randomization study

Abstract

Objective: The objective of this study was to investigate the causal relationship between the number of lifetime sexual

partners (NLSP) and cervical cancer (CC) using the Mendelian randomization (MR) method. Methods: Genome-wide

association study (GWAS) data on NLSP and CC were obtained from the integrative epidemiology unit open genome-wide

association studies (IEU OpenGWAS) project. To assess the correlation between NLSP and CC risk, we employed the

inverse-variance weighted (IVW) method, applying a preset threshold to select single nucleotide polymorphisms (SNPs)

closely related to NLSP. Instrumental variables (IVs) were constructed using isolated SNPs. Heterogeneity among the SNPs

was evaluated using the Cochran Q test. The presence of abnormal SNPs was tested with MR pleiotropy residual sum and

outlier test (MR-PRESSO). The Mendelian randomization-Egger (MR-Egger) intercept test was conducted to examine

horizontal pleiotropy among the SNPs. Additionally, the "leave-one-out" sensitivity analysis was performed to assess whether

the MR results were influenced by any single SNP. Results: A total of 63 SNPs correlated with NLSP were screened. IVW

analysis revealed no causal relationship between NLSP and CC, with an odds ratio (OR) of 1.001, 95% confidence interval

(CI): 0.996 – 1.005, P = 0.797. The Cochran Q test indicated no significant heterogeneity among the included SNPs (Q =

73.051, P = 0.07). The MR-Egger intercept value was 1.61×10-5 (P = 0.903), suggesting no genetic pleiotropy among the

screened SNPs. MR-PRESSO did not identify any outlier SNPs. Furthermore, the "leave-one-out" sensitivity analysis

indicated that the causal estimates were unlikely to be influenced by specific SNP effects. Conclusion: Our findings suggest

that there may be no causal relationship between the NLSP predicted by genetics and the risk of CC.