Point mutations and single nucleotide polymorphisms (SNPs) in the CDKN2A gene in bladder cancer patients have been resolved only to a limited extent. The exact frequency of mutations remains uncertain and reports on SNPs are lacking. In this population-based study we investigated mutations and polymorphisms in the CDKN2A gene in bladder cancer patients from all hospitals within the Stockholm County. Mutations were determined in 4 exons of the CDKN2A gene in tumor-tissues from 172 bladder cancer patients and 2 single nucleotide polymorphisms in the 3' UTR of the CDKN2A gene were studied in 309 cases. Missense mutations were identified in only 4 of 172 (2.3%) cases, including 1 in the germ-line. Frequencies of the 500 C-->G and 540 C-->T polymorphisms in the 3' UTR of the CDKN2A in bladder cancer cases were not statistically significantly different compared to an ethnically matched control population. The tumor-specific survival was significantly shorter in patients with either the 500 C-->G or 540 C-->T polymorphism than those with wild-type CDKN2A gene (P = 0.02). Our results corroborate the earlier findings that single base mutation is not the prime mode of inactivation of the CDKN2A gene in bladder cancer. Further, the results indicate, a role for the 3' UTR polymorphisms in the CDKN2A gene in tumor invasiveness.
Copyright 2002 Wiley-Liss, Inc.