Sex bias in FGFR3 somatic mutations in bladder cancer

Abstract Background Strong sex disparities have been observed among patients with bladder cancer (BCa). FGFR3 is one of the most frequently mutated genes in bladder cancer, and there are inconsistencies in its frequency in male and female patients. Methods Here, we conducted a meta-analysis comparing the FGFR3 somatic mutation frequency in men and women among 7351 patients with BCa from 18 cohorts. Results We showed that female patients had a 1.32 times higher risk of having FGFR3 somatic mutations than males. This difference was attributed to mutations occurring at the 2 most frequently mutated sites, S249 and Y375. Additionally, nonsense mutations were more likely to be found in women, whereas indel/frameshift mutations were almost exclusively found in men; however, no difference was noted for missense mutations. Conclusions A female sex bias in FGFR3 somatic mutations was observed in BCa. Well-powered individual participant data analyses addressing the possible confounding effects of other factors (eg, age, ethnicity, smoking status, muscle invasiveness, and molecular subtype), as well as analyses integrating omics and functional investigations, are warranted to further validate and explain the mechanisms of the current findings.