Epidemiology and Risk Factors for Testicular Cancer: A Systematic Review

Testicular germ cell tumors (TGCTs) are globally rare, although incidence significantly varies across global geographic regions and ethnicities. Recent decades have seen an unexplained increase in incidence. This review investigates the changing epidemiology of TGCT and identifies key risk factors.

A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement was conducted. After screening and risk-of-bias assessment, 53 reports on significant and updated topics on TGCT epidemiology and risk factors were included for narrative synthesis. Of these, 26 were selected for quantitative synthesis.

Projections suggest a continued increase in global TGCT incidence, even in populations with historically low incidence. Genetic predisposition, particularly single-nucleotide polymorphisms, accounts for approximately 44% of TGCT heritability. In utero exposure to endocrine-disrupting chemicals, cryptorchidism, infertility, high height, behavioral factors such as marijuana consumption, and environmental or occupational exposures to potentially harmful substances are associated with higher TGCT risk, with variable strength of evidence. Meta-analyses confirmed a significant association between prenatal/early-life risk factors and TGCT incidence (odds ratio 1.44). Limitations include constrained evidence quality, heterogeneity in study types, and a limited volume of data supporting each topic.

TGCT pathogenesis is influenced by genetic predisposition and exposures during early life. The rising incidence may reflect socioeconomic changes and migration patterns, which determine variation in population exposure to risk factors. TGCT epidemiology remains controversial and requires further research and the implementation of optimal screening programs considering the rising incidence and consequent impact on global health and socioeconomic systems.