Abstract
Purpose
Bladder urothelial carcinoma (bladder-UC) displays distinct genotypic differences compared to upper tract UC (UTUC). We recently reported specific 8q24 SNP variants confer susceptibility to UTUC and aggressive disease features. Herein, we evaluate a bladder-UC cohort to see whether similar polymorphisms are linked similarly same way with disease risk and aggressiveness.
Methods
231 bladder-UC patients and 261 benign controls were matched for gender, age, ethnicity and smoking habits. We retrospectively retrieved information on tumour stage, grade, size, multiplicity, carcinoma in situ and tumour number. DNA was extracted from paraffin-embedded primary bladder-UC samples and blood of benign controls. Genotyping of rs9642880[T] (8q24.1) and rs798766[T] (4p16.3) was performed using commercially available Taqman® assays and the ABI™ 7000 Sequence Detector.
Results
Using a case–control analysis, bladder-UC risk was increased in individuals carrying the T/T genotype of rs9642880 [OR = 1.72 (95 % CI 1.1–2.8); p = 0.028] and rs798766 [OR = 1.84 (95 % CI 0.9–2.3); p = 0.01]. When analysing parameters of bladder-UC aggressiveness, the T/T genotypes for rs9642880 and rs798766 were not found to be associated with either grade [OR = 0.89 (95 % CI 0.52–1.32; p = 0.68) and OR = 0.95 (95 % CI 0.58–1.48; p = 0.61), respectively] or pathological stage [OR = 0.79 (95 % CI 0.42–1.48; p = 0.46) and OR = 0.90 (95 % CI 0.49–1.61; p = 0.72), respectively]. SNP variability of rs9642880[T] and rs798766[T] is associated with an increased risk of bladder-UC but we did not find an association with disease aggressiveness as we did previously for UTUC.
Conclusions
This is further evidence of the distinct genetic differences that exist between bladder-UC and UTUC, and it is not possible to extrapolate results of genetic studies between these two urothelial disease entities.
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References
Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90
Catto JW, Yates DR, Rehman I et al (2007) Behavior of urothelial carcinoma with respect to anatomical location. J Urol 177:1715–1720
Catto JW, Azzouzi AR, Amira N et al (2003) Distinct patterns of microsatellite instability are seen in tumours of the urinary tract. Oncogene 22:8699–8706
Knowles MA (2008) Bladder cancer subtypes defined by genomic alterations. Scand J Urol Nephrol Suppl 218:116–130
Olfert SM, Felknor SA, Delclos GL (2006) An updated review of the literature: risk factors for bladder cancer with focus on occupational exposures. South Med J 99:1256–1263
Garcia-Closas M, Malats N, Silverman D et al (2005) NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish bladder cancer study and meta-analyses. Lancet 366:649–659
Gripp KW (2005) Tumor predisposition in Costello syndrome. Am J Med Genet C Semin Med Genet 137C:72–77
Aben KK, Witjes JA, Schoenberg MP et al (2002) Familial aggregation of urothelial cell carcinoma. Int J Cancer 98:274–278
McCullough DL, Lamm DL, McLaughlin AP et al (1975) Familial transitional cell carcinoma of the bladder. J Urol 113:629–635
Kiemeney LA, van Houwelingen KP, Bogaerts M et al (2006) Polymorphisms in the E-cadherin (CDH1) gene promoter and the risk of bladder cancer. Eur J Cancer 42:3219–3227
Gudmundsson J, Sulem P, Manolescu A et al (2007) Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet 39:631–637
Fletcher O, Johnson N, Gibson L et al (2008) Association of genetic variants at 8q24 with breast cancer risk. Cancer Epidemiol Biomark Prev 17:702–705
Houlston RS, Cheadle J, Dobbins SE et al (2010) Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33. Nat Genet 42:973–977
Kiemeney LA, Thorlacius S, Sulem P et al (2008) Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nat Genet 40:1307–1312
Rothman N, Garcia-Closas M, Chatterjee N et al (2010) A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nat Genet 42:978–984
Rafnar T, Sulem P, Stacey SN et al (2009) Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 41:221–227
Ghoussaini M, Song H, Koessler T et al (2008) Multiple loci with different cancer specificities within the 8q24 gene desert. J Natl Cancer Inst 100:962–966
Kiemeney LA, Sulem P, Besenbacher S et al (2010) A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. Nat Genet 42:415–419
Roupret M, Cancel-Tassin G, Comperat E et al (2007) Phenol sulfotransferase SULT1A1*2 allele and enhanced risk of upper urinary tract urothelial cell carcinoma. Cancer Epidemiol Biomark Prev 16:2500–2503
Zheng L, Wang Y, Schabath MB et al (2003) Sulfotransferase 1A1 (SULT1A1) polymorphism and bladder cancer risk: a case-control study. Cancer Lett 202:61–69
Hung RJ, Boffetta P, Brennan P et al (2004) GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population. Int J Cancer 110:598–604
Roupret M, Drouin SJ, Cancel-Tassin G et al (2012) Genetic variability in 8q24 confers susceptibility to urothelial carcinoma of the upper urinary tract and is linked with patterns of disease aggressiveness at diagnosis. J Urol 187:424–428
Roupret M, Catto J, Coulet F et al (2004) Microsatellite instability as indicator of MSH2 gene mutation in patients with upper urinary tract transitional cell carcinoma. J Med Genet 41:e91
Wang M, Zhang W, Yuan L et al (2009) Common genetic variants on 8q24 contribute to susceptibility to bladder cancer in a Chinese population. Carcinogenesis 30:991–996
Cortessis VK, Yuan JM, Van Den Berg D et al (2010) Risk of urinary bladder cancer is associated with 8q24 variant rs9642880[T] in multiple racial/ethnic groups: results from the Los Angeles-Shanghai case-control study. Cancer Epidemiol Biomark Prev 19:3150–3156
Golka K, Selinski S, Lehmann ML et al (2011) Genetic variants in urinary bladder cancer: collective power of the “wimp SNPs”. Arch Toxicol 85:539–554
Kiemeney LA, Grotenhuis AJ, Vermeulen SH et al (2009) Genome-wide association studies in bladder cancer: first results and potential relevance. Curr Opin Urol 19:540–546
Ioannidis JP, Thomas G, Daly MJ (2009) Validating, augmenting and refining genome-wide association signals. Nat Rev Genet 10:318–329
Wu X, Ye Y, Kiemeney LA et al (2009) Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer. Nat Genet 41:991–995
Safarinejad MR, Shafiei N, Safarinejad SH (2011) The association between bladder cancer and a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) gene. Arch Toxicol 85:1209–1218
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Yates, D.R., Rouprêt, M., Drouin, S.J. et al. Genetic polymorphisms on 8q24.1 and 4p16.3 are not linked with urothelial carcinoma of the bladder in contrast to their association with aggressive upper urinary tract tumours. World J Urol 31, 53–59 (2013). https://doi.org/10.1007/s00345-012-0954-6
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DOI: https://doi.org/10.1007/s00345-012-0954-6