We conducted a genome-wide SNP association study on 1,803
urinary bladder cancer (UBC) cases and 34,336 controls from
Iceland and the Netherlands using Illumina HumanHap300 and HumanCNV370-duo Beadchips. The 10 most significant SNPs were genotyped using Centaurus single track assays in 7 follow up case-control groups (2,165 cases and 3,800 controls) from Italy (Torino and Brescia), the UK, Belgium, Eastern Europe (Hungary, Romania and Slovakia), Sweden and Spain.
The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10-12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on 3q28 (allele-specific OR = 1.19; P = 1.15 x 10-7).
No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. Individuals with low risk tumors (i.e. confined to the bladder mucosa and not poorly differentiated) had a higher frequency of rs9642880[T] than individuals with high risk tumors (OR = 1.15, P = 0.011). No difference was found in the frequencies of rs9642880[T] between ever-smoking and never-smoking cases.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-7.
Seventh AACR International Conference on Frontiers in Cancer Prevention Research-- Nov 16-19, 2008; Washington, DC