FaCD Online Syndrome Fact Sheet

Last updated: 23 Jun 2008

Name: Bladder-, Ureter, Renal Pyelum Cancer, Familial Clustering of

Synonym: Urothelial Cancer, Familial, Transitional Cell Carcinoma of the Urinary Tract, Familial

Mode of Inheritance: multifact?

Tumor features

renal pyelum cancer
ureter cancer
urinary bladder cancer

Tumor features (possible)

leukemia
lymphoma, malignant (Non-Hodgkin and/or Hodgkin)

Non-tumor features (possible)

t(5;20)(p15;q11) (constitutional)

Comment

Familial clustering of bladder cancer has been reported[1-5] and may occur in approximately 4 % of cases[6]. Kantor et al.[6] demonstrated that having an affected first degree relative increases the risk of bladder cancer and smoking modifies this this. The authors reported relative risks of 2.7, 1.7 and 1.3 depending on the age at diagnosis of the tumor: below age 45, ages 45-64 and 65 and older, respectively. Cigarette smoking in the setting of a family history of bladder cancer was shown to strongly increase the risk of developing this tumor. Relative risks of up to 28.1 in heavy smokers (60 + cigarettes/day) were calculated as compared to a relative risk (RR) of 2.1 in heavy smokers with a negative family history. Non-smokers with a positive family history still had a RR of 1.5 and this observation of a familial component independent of smoking was supported by the findings of Kramer et al.[7] who reported a RR of 1.8 for a similar group. In another case-control series, individuals who had smoked and who also had a positive family history of bladder cancer were at 5-fold increased risk to develop this type of cancer, compared with individuals who never smoked and who had no family history of bladder cancer[23]. Increased mutagen sensitivity appears to be no biomarker to identify strong familial clustering of urothelial cancer[21].

Piper et al.[8] found bladder or renal cancer in first-degree relatives not to be a risk factor for bladder cancer in young women (< 50 yrs.). A Dutch population-based family case-control study in patients with newly diagnosed with urothelial cancer of the bladder, ureter, renal pelvis or urethra revealed an almost 2-fold increased risk among first-degree relatives of patients with urothelial cancer, which could not be explained by smoking[20]. The same study also demonstrated a similar risk increase for cancer of the hematolymphopoietic system among case-relatives[20]. A family history of cancer in general has been reported to be a risk factor in the development of bladder cancer[2].

A range of gene variants modify the risk for these tumors (e.g. see 9-14 and a recent review in 24]. They are not listed separately in this file. A small number of published families suggest mendelian predisposition to urinary tract cancer [3,5,15,24]. Familial clustering of transitional cell carcinomas (TCC) at different sites of the urinary tract has been observed[5;16;17], including familial cancer of the ureter[18]. Strong evidence of Mendelian inheritance of urothelial cancer through a single major gene was not found in segregation analysis of a series of 1193 families with urothelial cancer. However, none of the Mendelian models could be rejected[22]. A germline translocation (5;20)(p15;q11) has been observed in a 29-years-old man with TCC bladder cancer. His mother had been diagnosed with a similar tumor (she was not karyotyped)[19].

References

[1] Lynch HT, Kimberling WJ, Lynch JF, Brennan K. Familial bladder cancer in an oncology clinic. Cancer Genet Cytogenet 1987; 27(1):161-165.
[2] Bravo MP, Del Rey-Calero J, Conde M. Risk factors of bladder cancer in Spain. Neoplasma 1987; 34(5):633-637.
[3] Lynch HT, Walzak MP, Fried R, Domina AH, Lynch JF. Familial factors in bladder carcinoma. J Urol 1979; 122(4):458-461.
[4] Purtilo DT, McCarthy B, Yang JP, Friedell GH. Familial urinary bladder cancer. Semin Oncol 1979; 6(2):254-256.
[5] Kiemeney LALM, Schoenberg M. Familial transitional cell carcinoma. J Urol 156[3], 867-872. 1996.
[6] Kantor AF, Hartge P, Hoover RN, Fraumeni jr JF. Familial and environmental interactions in bladder cancer risk. Int J Cancer 1985; 35(6):703-706.
[7] Kramer AA, Graham S, Burnett WS, Nasca P. Familial aggregation of bladder cancer stratified by smoking status. Epidemiology 1991; 2(2):145-148.
[8] Piper JM, Matanoski GM, Tonascia J. Bladder cancer in young women. Am J Epidemiol 123[6], 1033-1042. 1986.
[9] Herring DW, Cartwright RA, Williams DDR. Genetic associations of transitional cell carcinoma. Br J Urol 1979; 51:73-77.
[10] Maher ER. Genetics of urological cancers. Br Med Bull 1994; 50:698-707.
[11] Branch RA, Chern HD, Adedoyin A, Romkes-Sparks M, Lesnick TG, Persad R, Wilkinson GR, Fleming CM, Dickinson AJ, Sibley G, Smith P. The procarcinogen hypothesis for bladder cancer: Activities of individual drug metabolizing enzymes as risk factors. Pharmacogenetics 1995; 5:S97-S102.
[12] Ross RK, Jones PA, Yu MC. Bladder cancer epidemiology and pathogenesis. Semin Oncol 23[5], 536-545. 1996.
[13] Schulte PA. The role of genetic factors in bladder cancer. Cancer Detect Prev 1988; 11:379-388.
[14] Krontiris TG, Devlin B, Karp DD, Robert NJ, Risch N. An association between the risk of cancer and mutations in the HRAS1 minisatellite locus. N Engl J Med 1993; 329(8):517-523.
[15] Mahboubi AO, Ahlvin RC, Mahboubi EO. Familial aggregation of urothelial carcinoma. J Urol 1981; 126(5):691-692.
[16] Orphali SLJ, Shols GW, Hagewood J, Tesluk H, Palmer JM. Familial transitional cell carcinoma of renal pelvis ans upper ureter. Urology 1986; 5:394-396.
[17] Kiemeney LA, Moret NC, Witjes JA, Schoenberg MP, Tulinius H. Familial transitional cell carcinoma among the population of Iceland. J Urol 157[5], 1649-1651. 1997.
[18] Burkland CE, Juzek RH. Familial, occurrence of carcinoma of the ureter. J Urol 1966; 96:697-701.
[19] Schoenberg M, Kiemeney L, Walsh PC, Griffin CA, Sidransky D. Germline translocation t(5;20)(p15;q11) and familial transitional cell carcinoma. J Urol 1996; 155:1035-1036.
[20] Aben KK, Witjes JA, Schoenberg MP, Hulsbergen-van de Kaa C, Verbeek AL, Kiemeney LA. Familial aggregation of urothelial cell carcinoma. International journal of cancer 2002; 98(2):274-8.
[21] Aben KK, Cloos J, Koper NP, Braakhuis BJ, Witjes JA, Kiemeney LA. Mutagen sensitivity in patients with familial and non-familial urothelial cell carcinoma. International journal of cancer 2000; 88(3):493-6.
[22] Aben KK, Baglietto L, Baffoe-Bonnie A, Coebergh JW, Bailey-Wilson JE, Trink B, Verbeek AL, Schoenberg MP, Alfred Witjes J, Kiemeney LA. Segregation analysis of urothelial cell carcinoma. European journal of cancer 2006; 42(10):1428-33.
[23] Lin J, Spitz MR, Dinney CP, Etzel CJ, Grossman HB, Wu X. Bladder cancer risk as modified by family history and smoking. Cancer 2006; 107(4):705-11.
[24] Mueller CM, Caporaso N, Greene MH. Familial and genetic risk of transitional cell carcinoma of the urinary tract. Urologic oncology 2008;epub ahead of print.