Familial aggregation of urothelial cell carcinoma

Urothelial cell carcinoma (UCC) is not considered to be a familial disease. Familial clustering of UCC was described in several case reports, however, some with an extremely early age at onset suggesting a genetic component. Epidemiological studies yielded inconsistent evidence of familial UCC, possibly because of low power and the inability to adjust for strong confounding. In our study the existence of a familial subtype of UCC was evaluated, as well as familial clustering of UCC with other types of cancer. A population-based family case-control study was performed including patients newly diagnosed with UCC of the bladder, ureter, renal pelvis or urethra, between January 1995 and December 1997, in the southeastern part of the Netherlands. Information on the patients' first-degree relatives was collected by postal questionnaire and subsequent telephone calls. The patients' partners filled out a similar questionnaire on their relatives. All reported occurrences of UCC were verified using medical records. Disease occurrence among case-relatives and control-relatives was compared to obtain the familial risk. Random effect proportional hazards regression analyses were used to calculate this familial risk while adjusting for age, gender and smoking behavior. In 95 families of the 1,193 patients and in 36 families of the 853 partners at least 1 relative was diagnosed with UCC. This yielded an adjusted hazard ratio (HR) of 1.8 (95% CI: 1.3-2.7). An increased risk was also found for cancer of the hematolymphopoietic system (hazard ration = 1.9, 95% CI: 1.2-3.1) among case-relatives. These results indicate that UCC has a familial component with an almost 2-fold increased risk among first-degree relatives of patients with UCC, which cannot be explained by smoking. Future segregation analyses may indicate whether this clustering can be attributed to genetic susceptibility.