Abstract
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. © 2002 Wiley‐Liss, Inc.