Segregation analysis of urothelial cell carcinoma

Eur J Cancer. 2006 Jul;42(10):1428-33. doi: 10.1016/j.ejca.2005.07.039. Epub 2006 Jun 5.


A family history of urothelial cell carcinoma (UCC) confers an almost two-fold increased risk of developing UCC. It is unknown whether (part of) this aggregation of UCC has a Mendelian background. We performed complex segregation analyses on 1193 families ascertained through a proband with UCC of the bladder, ureter, renal pelvis or urethra, who were newly diagnosed between January 1, 1995 and December 31, 1997 and registered by two population-based cancer registries in the southeastern part of the Netherlands. Data were reported on 10 738 first-degree relatives by postal questionnaire; 101 of these relatives had UCC. All reported occurrences of UCC were verified (if possible) using medical records. Analyses were performed with the S.A.G.E. segregation package. Five restricted models (Mendelian dominant, Mendelian recessive, Mendelian co-dominant, 'no major gene' model and environmental model) were tested against the general unrestricted model. Sex and smoking status were incorporated as covariates. Strong evidence of Mendelian inheritance of UCC through a single major gene was not found in these 1 193 families. However, since none of the Mendelian models could be rejected, an inherited subtype of UCC cannot be excluded. A major gene may segregate in some families but this effect may have been masked in a background of high sporadic incidence. The 'no major gene' (or sporadic) model appeared to be the most parsimonious one to describe the occurrence of UCC in these families.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Humans
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Pedigree
  • Urologic Neoplasms / epidemiology
  • Urologic Neoplasms / genetics*