Brain and Central Nervous System Cancer in Older Adults: Global Burden, Genetic–Environmental Risk, and Inflammation‐Related Insights
Qiang Fu, Zhihao Xie, Tuhetiaji Tuerhongjiang, Zening Wang, Aierpati Maimaiti, Zhongwen Guo, Lin Pan, Haiqin Gao, Yongxin WangBackground
Aging has always been recognized as a significant risk factor for brain and central nervous system (CNS) cancers, but its mechanism and population‐level impact remain unclear.
Methods
Using the Global Burden of Disease (GBD) 2021 data, we evaluated incidence, prevalence, deaths, and disability‐adjusted life years (DALYs) for brain and CNS cancers among adults aged ≥ 55 years in 204 countries and territories from 1990 to 2021. We assessed temporal trends, regional patterns, projections, and frontier performance. Summary data‐based Mendelian randomization (SMR) was used to examine a prespecified Human CellAge cellular‐senescence gene panel using brain eQTL and mQTL data. Two‐sample MR evaluated 14 environmental phenotypes.
Results
In 2021, adults aged ≥ 55 years accounted for 198,802 incident cases, 354,677 prevalent cases, 167,070 deaths, and 3,811,333 DALYs globally. Absolute‐count and crude‐rate rankings differed among the 21 GBD regions. East Asia had the largest counts for all four measures; Western Europe had the highest crude incidence rate, high‐income Asia Pacific the highest crude prevalence rate, and Central Europe the highest crude death and DALY rates. SMR identified associations involving TERT, CDKN2A, CDKN2B, and EGFR. A nominal association was observed for nitrogen oxide air pollution in the primary MR analysis (OR 2.44, 95% CI 1.16–5.13; p = 0.018), but it did not meet the Bonferroni threshold and was not statistically significant in the secondary FinnGen R12 analysis (OR 1.34, 95% CI 0.72–2.46).
Conclusion
Brain and CNS cancers imposes a substantial and geographically heterogeneous burden among adults aged ≥ 55 years. The SMR findings are consistent with established brain‐tumor loci, whereas the nitrogen oxide association remains hypothesis‐generating because it did not survive multiple‐testing correction and was not statistically significant in the secondary FinnGen R12 analysis.