Abstract 4680: Exploring the relationships between genetic variants within the UGT1A locus, cellular detoxification and risk of bladder cancer

摘要: Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL A recent genome-wide association study (GWAS) for urinary bladder cancer (UBC) has identified multiple novel genetic risk factors (Rothman et. al, Nat Gen, 2010). One of these was an intronic SNP rs11892031 (p=1.0×10-7) located within the UGT1A locus on chromosome 2q37. The human cellular detoxification uridine 5’ diphosphate (UDP)-glucuronosyltransferases (UGTs) belong to a superfamily proteins that conjugate diverse endo and exotoxins, increase their solubility facilitate removal via bile urine. includes nine protein-coding genes four pseudogenes. Each first exon is regulated by its own promoter spliced constant exons producing proteins. Due complexity region ∼90-95% similarity between substrate-binding 1 sequences genes, this poorly represented in public databases (HapMap, 1000 Genomes, dbSNP). To ensure specificity detection, we generated long-range amplicons sequenced all HapMap individuals (CEU) 44 patients 25 non-synonymous coding variations. All variations have been genotyped cases controls from Spanish Bladder Cancer Study (SBCS). We found one exonic showed stronger than original GWAS variant, variants some evidence gene cigarette smoking interactions. Having ∼20 potentially functional region, are exploring methods simultaneous analysis individual haplotypes. In conclusion, confirms altered environmental substrates important factor development cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings American Association Research; 2011 2-6; FL. Philadelphia (PA): AACR; Res 2011;71(8 Suppl):Abstract nr 4680. doi:10.1158/1538-7445.AM2011-4680