Highlight report: Functional consequences of urinary bladder cancer risk variants

Silvia Selinski1[*]

1Leibniz Research Centre for Working Environment and Human Factors, Dortmund/Germany

EXCLI J 2013;12:Doc1017


About 180,000 new cases of urinary bladder cancer are diagnosed each year in the European Union. The most relevant risk factors are occupational exposure to aromatic amines and cigarette smoking (Golka et al., 2012[8]; Ovsiannikov et al., 2012[17]; Selinski et al., 2013[23]; Kempkes et al., 1996[12]). Recently, genome-wide association studies have successfully identified several urinary bladder cancer susceptibility loci (review: Dudek et al., 2013[4]; Golka et al., 2011[10]; Selinski, 2012[22]; Bolt, 2013[1][2]). Currently confirmed genetic variants include rs9642880 (MYC, Kiemeney et al., 2008[14]; Golka et al., 2009[9]), rs710521 (TP63, Kiemeney et al., 2008[14]; Lehmann et al., 2010[15]), rs401681 and rs2736098 (CLPTM1L, TERT, Rafnar et al., 2009[18]), rs2294008 and rs2978974 (PSCA, Wu et al., 2009[27]; Fu et al., 2012[5]), rs798766 (TACC3, FGFR3, Kiemeney et al., 2010[13]), rs11892031 (UGT1A, Rothman et al., 2010[20]; Selinski et al., 2012[25]), rs17863783 (UGT1A6, Tang et al., 2012[26]), rs1495741 (NAT2, Rothman et al., 2010[20]; Garcia-Closas et al., 2011[6]; Selinski et al., 2011[24]), rs8102137 (CCNE1, Rothman et al., 2010[20]), rs1014971 (CBX6, Rothman et al., 2010[20]) and rs17674580 and rs1058396 (SLC14A1, Rafnar et al., 2011[19]). Moreover, it has been shown that several high risk alleles of single nucleotide polymorphisms can interact leading to enhanced odds ratios (Schwender et al., 2012[21]). However, relatively little is known about the functional consequences of the novel bladder cancer susceptibility SNPs. Many of them are located in non-coding regions. An example is rs9642880 on chromosome 8q24 that is approximately 30kb upstream of MYC (Kiemeney et al., 2008[14]). Similarly, rs1014971 on 22q13.1 is located 25 kb and 64kb from APOBEC3A and CBX6, respectively (Rothman et al., 2010[20]). Considering these relatively large distances between both SNPs and the closest exons it seems unlikely that an influence can be explained by linkage disequilibrium. Recently, Dudek and colleagues have addressed the open question of the functional consequences of urinary bladder susceptibility loci (Dudek et al., 2013[4]). At least two risk variants, located in PSCA and UGT1A, were confirmed to have functional consequences.

The current review article of Dudek et al. (2013[4]) describes in a comprehensive way the current concepts by which mechanisms the recently identified bladder cancer risk loci may contribute to carcinogenesis.



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[*] Corresponding Author:

Silvia Selinski, Leibniz Research Centre for Working Environment and Human Factors, Dortmund/Germany, eMail: Selinski@ifado.de