ArticleCarcinogenesis2017
Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer.
Article in Carcinogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association of Glutathione S-transferase gene polymorphism with bladder Cancer susceptibility.BMC cancer · 2018Pooled it
- Urea Transporters in Cancer: Emerging Roles and Their Clinical Implications.Biomedicines · 2025Review
- Urea Transporters and Their Gene Mutations in Diseases.Sub-cellular biochemistry · 2025Review
- Familial Risk and Interaction With Smoking and Alcohol Consumption in Bladder Cancer: A Population-Based Cohort Study.World journal of oncology · 2023Article
- Bladder cancer course, four genetic high-risk variants, and histopathological findings.EXCLI journal · 2023Article
- Interaction between blood pressure and genetic risk score for bladder cancer, and risk of urothelial carcinoma in men.Scientific reports · 2022Article
- The impact of genetic variants in theFrontiers in endocrinology · 2022Article
- Additions.Deutsches Arzteblatt international · 2021Article
- A Rabbit Monoclonal Antibody against the Antiviral and Cancer Genomic DNA Mutating Enzyme APOBEC3B.Antibodies (Basel, Switzerland) · 2019Article
- A Case-Control Study of the Association Between the SPP1 Gene SNPs and the Susceptibility to Breast Cancer in Guangxi, China.Frontiers in oncology · 2019Article
- Additional evidence for the 'wimp SNP' concept of carcinogenesis.EXCLI journal · 2017Article
- Highlight report: Occupational urinary bladder cancer.EXCLI journal · 2017Article
- Discovering urinary bladder cancer risk variants: Status quo after almost ten years of genome-wide association studies.EXCLI journal · 2017Article
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Abstract
Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case-control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case-control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations. Pooled analysis of the two studies as discovery group (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant combinations by a logistic regression approach. The New England and Spanish Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication series. Twelve previously identified risk variants were considered. The strongest four-variant combination was obtained in never smokers. The combination of rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4 (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC, CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95% CI = 1.93-3.47; P = 1.87 × 10-10), while the individual variant ORs ranged only between 1.11 and 1.30. The combination replicated in the New England and Spanish Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10-2.33; P = 0.013). The four-variant combination is relatively frequent, with 25% in never smoking cases and 11% in never smoking controls (total study group: 19% cases, 14% controls). In conclusion, we show that four high-risk variants can statistically interact to confer increased bladder cancer risk particularly in never smokers.
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