Association between multiple sclerosis and cancer risk: An extensive review/meta and Mendelian randomization analyses

Observational investigations examining cancer risk among multiple sclerosis (MS) patients have produced contradictory findings. Herein, we performed an extensive review and meta-analysis to evaluate the correlation and causation between MS and cancer incidence.We systematically screened for published articles examining cancer incidences among MS patients within the Cochrane Library, PubMed, and Embase databases. Next, we employed STATA v.16.0 for data analysis. Following meta-analysis, we performed a two-sample Mendelian randomization (MR) analysis to uncover the underlying mechanism behind the MS-mediated regulation of certain cancers.Overall, we selected 18 articles encompassing 14 individual cancers incidences and a total of 368,952 patients for meta-analysis. Based on our analysis, there was reduced pancreatic (ES = 0.68; 95% CI: 0.49-0.93; I 2 = 0%) and ovarian cancer (ES = 0.65; 95% CI: 0.53-0.80; I 2 = 86.7%) co-occurrences among MS patients. Meanwhile, the incidences of breast (ES = 1.10; 95% CI: 1.01-1.21; I 2 = 60.9%) and brain cancers (ES = 1.94; 95% CI: 1.12-3.37; I 2 = 56.1%) were elevated among the same population. However, MR analysis revealed the opposite relation between MS and breast cancer risk (OR = 0.94392; 95% CI: 0.91011-0.97900, P = 0.002). Moreover, it revealed strong incidence of lung cancer (OR = 1.0004; 95% CI: 1.0001-1.0083, P = 0.001) among MS patients, as evidenced by the inverse variance weighting estimator. Lastly, MR found that other forms of cancers were not significantly related to MS.Using meta-analysis, we demonstrated that MS patients exhibited enhanced pancreatic and ovarian cancer risk, and diminished breast and brain cancer risk. However, using MR analysis, we discovered an inverse relation between MS and breast cancer risk, and additionally saw an uptick in lung cancer co-occurrence among MS patients.