Prostate Gene Polymorphism Linked to Bladder Cancer
Margaret R. Karagas, Ph.D.,
Dartmouth Medical School
NIEHS Grants P42ES007373
A fifty-member, international and interdisciplinary team of researchers report the discovery of a single nucleotide polymorphism in the prostate stem cell antigen gene (PSCA) as a urinary bladder cancer gene. The research team includes NIEHS grantees from the M.D. Anderson Cancer Center and Dartmouth University.
The group conducted a genome-wide association study on 969 bladder cancer cases from Texas. This study was combined with ongoing efforts in three other US populations and nine European groups. A consistent association of a missense variant in the PSCA gene dubbed rs2294008 was found with bladder cancer in all populations. In combining all study subjects, the number of participants included 6,667 cases of bladder cancer and 35,590 controls and produced a highly statistically significant result.
The missense variant alters the start codon, is thought to shorten the protein by nine amino acids, and reduces promoter activity. Resequencing the PSCA genomic region identified rs2294008 as the only common missense polymorphism in the gene. Recent studies demonstrated that the same alteration is associated with gastric cancer in an Asian population. Whether this is true for people of European descent, remains to be seen. Additional studies are planned to determine the physiological significance and functional consequences of the variant gene.
Citation: Wu X, Ye Y, Kiemeney LA, Sulem P, Rafnar T, Matullo G, Seminara D, Yoshida T, Saeki N, Andrew AS, Dinney CP, Czerniak B, Zhang ZF, Kiltie AE, Bishop DT, VineisP, Porru S, Buntinx F, Kellen E, Zeegers MP, Kumar R, Rudnai P, Gurzau E, KoppovaK, Mayordomo JI, Sanchez M, Saez B, Lindblom A, de Verdier P, Steineck G, Mills GB, Schned A, Guarrera S, Polidoro S, Chang SC, Lin J, Chang DW, Hale KS, Majewski T, Grossman HB, Thorlacius S, Thorsteinsdottir U, Aben KK, Witjes JA,Stefansson K, Amos CI, Karagas MR, Gu J. Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer. Nat Genet. 2009 Sep;41(9):991-5.
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