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.
OBJECTIVE
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.
Academic Department of Urology and Pathology of la Pitié-Salpêtrière, Tenon Hospital, Groupe Hospitalo-Universitaire Est, Assistance Publique, Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris VI, Paris, France. d.yates@sheffield.ac.uk
David R
DR
Yates
Morgan
M
Rouprêt
Sarah J
SJ
Drouin
Marie
M
Audouin
Géraldine
G
Cancel-Tassin
Eva
E
Comperat
Marc-Olivier
MO
Bitker
Olivier
O
Cussenot
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D007682:Kidney Pelvis; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D014516:Ureteral Neoplasms / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology