Rs11892031[A] on chromosome 2q37 in an intronic region of the UGT1A locus is associated with urinary bladder cancer risk

Abstract

Recently, rs11892031[A] has been identified in a genome-wide association study (GWAS) to confer increased risk of urinary bladder cancer (UBC). To confirm this association and additionally study a possible relevance of exposure to urinary bladder carcinogens, we investigated the IfADo UBC study group, consisting of eight case-control series from different regions including 1,805 cases and 2,141 controls. This analysis was supplemented by a meta-analysis of all published data, including 13,395 cases and 54,876 controls. Rs11892031 A/A was significantly associated with UBC risk in the IfADo case-control series adjusted to cigarette smoking, gender, age and ethnicity (OR = 1.18; 95% CI = 1.02-1.37; P = 0.026). In the meta-analysis, a convincing association with UBC risk was obtained (OR = 1.19; 95% Cl = 1.12-1.26; P < 0.0001). Interestingly, the highest odds ratios were obtained for individual case-control series with a high degree of occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines: cases with suspected occupational UBC (OR = 1.41) and cases from the highly industrialized Ruhr area (OR = 1.98) compared with Ruhr area controls (all combined OR = 1.46). Odds ratios were lower for study groups with no or a lower degree of occupational exposure to bladder carcinogens, such as the Hungary (OR = 1.02) or the ongoing West German case-control series (OR = 1.06). However, the possible association of rs11892031[A] with exposure to bladder carcinogens still should be interpreted with caution, because in contrast to the differences between the individual study groups, interview-based data on occupational exposure were not significantly associated with rs11892031. In conclusion, the association of rs11892031[A] with UBC risk could be confirmed in independent study groups.

Distinct SNP Combinations Confer Susceptibility to Urinary Bladder Cancer in Smokers and Non-Smokers

“…It is well established that a deletion variant of the detoxifying phase II metabolizing enzyme glutathione S-transferase M1 ( GSTM1 ), in addition to N-acetyltransferase 2 ( NAT2 ) slow acetylation are associated with increased urinary bladder cancer risk [2]–[6]. Recently, further genetic variants have been identified and validated in several genome-wide association studies [7]–[12] and were extended to occupational exposure [13]–[15].…”

Phase II Drug-Metabolizing Polymorphisms and Smoking Predict Recurrence of Non–Muscle-Invasive Bladder Cancer: A Gene–Smoking Interaction

“…A genome-wide association study also identified the UGT1 locus as a susceptibility gene associated with bladder cancer risk (16), an observation supported by subsequent studies (33,34). No study has reported, so far, the potential prognostic value of the common UGT1A1 promoter variant associated with mild hyperbilirubinemia (i.e., Gilbert syndrome) on bladder cancer recurrence.…”

Glucuronidation and UGT isozymes in bladder: new targets for the treatment of uroepithelial carcinomas?

“…Therefore, people with the genetic variant rs11892031 may have a greater risk of developing bladder cancer [18]. To further examine the association of rs11892031 with bladder cancer, Selinski et al analyzed eight case-control studies including 1,805 cases and 2,141 controls from the IfADo UBC study group and further supplemented this data with a meta-analysis of all published data, including 13,395 cases and 54,876 controls [25]. The results of this analysis confirmed the genome-wide association study (GWAS) by Rothman, which identified the association between rs11892031 and bladder cancer [25].…”

“…To further examine the association of rs11892031 with bladder cancer, Selinski et al analyzed eight case-control studies including 1,805 cases and 2,141 controls from the IfADo UBC study group and further supplemented this data with a meta-analysis of all published data, including 13,395 cases and 54,876 controls [25]. The results of this analysis confirmed the genome-wide association study (GWAS) by Rothman, which identified the association between rs11892031 and bladder cancer [25]. The GWAS of bladder cancer prompted further fine mapping of the UGT1A locus, which allowed Tang et al to identify a SNP rs17863783 [19].…”