Bladder cancer survival in patients with NOD2 or CDKN2A variants

Oncotarget. 2022 Apr 22:13:628-640. doi: 10.18632/oncotarget.28226. eCollection 2022.


Purpose: The association between the NOD2 c.3020insC allele and CDKN2A missense variant c.442G>A (p.P.A148T) and survival of patients with bladder or kidney cancer remains controversial.

Materials and methods: We compared the allele frequencies of NOD2 c.3020insC and CDKN2A p.A148T allele in 706 patients with bladder cancer, 410 cases with kidney cancer against two control groups. The Cox proportional hazards model was used to determine whether there were any survival differences between carriers of the NOD2 c.3020insC or the CDKN2A p.A148T variant.

Results: Among the three patient subgroups: patients under 60 years of age, non-smokers and a third with histological features of low grade noninvasive papillary bladder cancer, we observed that the c.3020insC allele had a nominal statistically significant effect on survival. We also observed that the NOD2 c.3020insC variant was more frequent in patients with bladder cancer aged between 51 and 60 years. There was some nominal evidence that the CDKN2A p.A148T polymorphism reduced survival in the subgroup of bladder cancer patients under 60 years of age. We observed that in kidney cancer patients, the incidence of the NOD2 variant appeared to be lower in the group aged between 60 and 70 years, however, this was not statistically significant. In addition, in patients with histological features of grade III chromophobic kidney cancer, the c.3020insC allele also appeared to be over-represented but this too was not statistically significant.

Conclusion: We have shown that the NOD2 c.3020insC allele and the CDKN2A p.A148T polymorphism does not play a role in the survival of patients with bladder cancer.

Keywords: CDKN2A; NOD2; bladder cancer; kidney cancer; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Kidney Neoplasms*
  • Middle Aged
  • Nod2 Signaling Adaptor Protein / genetics
  • Urinary Bladder
  • Urinary Bladder Neoplasms* / genetics


  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein