The HRAS1 variable number of tandem repeats (VNTR) polymorphism, 1 kb downstream from the HRAS1 gene, has been reported to be associated with risk of various cancers. To examine whether individuals with rare HRAS1 VNTR alleles are at increased risk of bladder cancer we carried out a case control study with 230 bladder cancer cases and 203 hospital-based controls frequency-matched on ethnicity, gender and age. For genotyping we used a PCR-based long-gel electrophoretic assay that provides precise allele size discrimination. We did not find evidence of a strong overall effect of the HRAS1 VNTR on bladder cancer risk. Genotype data for whites and blacks were analyzed separately, but the number of black subjects was too small to estimate meaningful odds ratios. Compared to white subjects with 2 common alleles, the odds ratio (OR) for white subjects with 1 rare allele was 0.9 (95% confidence interval (CI) ؍ 0.5-1.4) and for those with 2 rare alleles OR ؍ 1.7 (95% CI ؍ 0.6 -5.4). HRAS1 genotype may be related to the prognosis of bladder cancer, however, because incident cases, i.e., newly diagnosed cases had a higher frequency of rare alleles than did prevalent cases, i.e., cases already existing at the time of recruitment. Repeating the analyses with incident cases only (n ؍ 53), the OR for subjects with 1 rare allele was 1.2 (95% CI ؍ 0.6 -2.4) and for those with 2 rare alleles 3.2 (95% CI ؍ 0.8 -13.7). The number of incident cases was too small to draw firm conclusions on a possible association with a subgroup of tumors with a poor prognosis. Rare alleles of the HRAS1 minisatellite, or variable number of tandem repeat (VNTR), have been associated with risk of various cancers, including bladder cancer. 1 The HRAS1 VNTR maps 1 kb downstream from the polyadenylation signal of the human protooncogene HRAS1 and is comprised of 30 -100 tandemly repeated copies of a 28-base pair (bp) consensus motif. 2 The 4 most common alleles, a1, a2, a3 and a4, 3 have sizes of 1.0 kb, 1.45 kb, 2.05 kb and 2.5 kb, respectively 4 and have a combined allele frequency of 94% in the US population. 1 More than 40 other allelic variants have been described: the 'rare alleles.' Lineage analysis indicates that all rare alleles are derived from the common alleles, usually the one nearest in size. 5 Rare alleles differ from the common alleles in the number of repeats and have slight internal sequence variations in the 28-bp consensus sequence. 6 Several explanations have been proposed for the relationship between the HRAS1 VNTR and cancer risk. The HRAS1 VNTR binds at least 4 members of the rel/NF-B family of transcriptional regulatory factors, 7 suggesting that the VNTR could affect cancer susceptibility by transcriptional modulation of HRAS1 or other nearby genes. Interestingly, some allele-specific effects have been observed: the rare a2.1 allele possessed a 2-fold greater enhancer activity than the common a1 and a2 alleles. 8 In lung cancer patients rare HRAS1 alleles have been shown to be associated with microsatellite instabilit...