Introduction
Prostate cancer (PCa) is one of the most common cancers and the fifth leading cause of cancer death in men (1). In 2022, the American Cancer Society estimated 268,490 new cases of prostate cancer and 34,500 mortalities (2).
Multiple sclerosis (MS) is an immune-related disease of the central nervous system (3), with a high rate of teratogenicity (4) and mortality (5) and its associated complications are the leading causes of mortality, including infections, respiratory failure, and cardiovascular diseases. Previous studies have shown a strong relationship between immune-related disorders and cancer (6,7). While some studies show an increase risk of cancer in individuals with MS, others show the opposite or no association at all (8,9).
Results on the association between MS and PCa are conflicting. For instance, Bosco-Lévy et al (10) suggested that MS was associated with an increased risk of PCa [hazard ratio (HR)=2.08; 95% CI: 1.68-2.58], while Kingwell et al (11) showed that MS was not associated with the risk of PCa [standardized incidence ratio (SIR)=0.91; 95% CI: 0.64-1.27]. Marrie et al (12) showed different results. To address this problem, a meta-analysis was performed to clarify the relationship between MS and risk of PCa.
Discussion
The first comprehensive meta-analysis on the relationship between MS and PCa risk was published in 2015 (20), suggesting that MS reduced PCa risk. Notably, a study published in Cancer Hematology Review in 2016 also reported MS is associated with the reduction of PCa risk (21), while a cohort study in 2020 summing up more than 6,800 patients showed that during an average follow-up of 65 years, MS was not associated with PCa risk. However, a recent cohort study in 2022 found that MS increased the risk of PCa (10).
The risk of PCa in patients with MS is unknown and may be related to genetic and environmental factors, such as chronic inflammation and infection (22), which can cause tumor growth and escape by interfering with normal immune surveillance. Previous studies have shown that regulatory T-cell function is significantly impaired in patients with MS compared to normal function (23) and that regulatory T-cells can both promote tumorigenesis and inhibit the growth of some inflammatory tumors (24). Hormones also play an important role in patients with MS; studies have shown that testosterone levels are significantly lower in patients with MS and due to the significant anti-inflammatory properties of testosterone, some patients with MS opt for testosterone supplementation therapy, which may also have a relevant impact on PCa development due to the complex mechanism of action of testosterone (25–28). The treatment of MS may lead to the loss of immune protection against cancer or the activation of the immune system, making it a primary tumor (29). Moreover, the possible reasons include that studies conducted in different countries may have different factors that affect the results. For example, common risk factors for PCa include being elderly (30), diet (31) and independent protective factors including regular screening for PCa.
The present meta-analysis builds on previous meta-studies. Ghajarzadeh et al (32) summarized studies up to September 2019 and calculated a pooled RR estimate of 0.79 for cancer in patients with MS, thus they concluded that patients with MS would have a reduced risk of cancer. Nevertheless, due to the small number of studies, they did not summarize the PCa risk data, and no subgroup analysis was performed. Therefore the present study became necessary and it found a significant negative association between MS and PCa risk in subgroup analysis adjusted for confounders, suggesting that some of the confounders may also confound the results.
The present study found strong heterogeneity. Possible reasons for this are: First, the number of studies was relatively small (eight studies). Second, the sample sizes were different across the studies. Finally, the reasons may be related to geographic region, with no reports of PCa risk in Asia. In addition, different types of studies, including cohort studies and controlled case studies, and differences in study populations may be other sources of heterogeneity.
Overall, the present study was the most recent and comprehensive study on the association between MS and PCa risk. Its conclusions are meaningful, and the results of the subgroup and sensitivity analyses further validate the reasonableness and reliability of the findings.
However, the present study had several limitations. First, the number of studies was relatively small. Second, different study methods and social factors of different study populations may also cause heterogeneity. Finally, observational studies themselves may be subject to information bias. Therefore, future high-quality studies should address these issues comprehensively.
In summary, the present study demonstrated there was no significant association between MS and PCa risk, and the correlation between treatment modalities and PCa needs to be further explored in the future.