TY - JOUR
T1 - Segregation analysis of urothelial cell carcinoma
AU - Aben, Katja K.H.
AU - Baglietto, Laura
AU - Baffoe-Bonnie, Agnes
AU - Coebergh, Jan Willem W.
AU - Bailey-Wilson, Joan E.
AU - Trink, Barry
AU - Verbeek, André L.M.
AU - Schoenberg, Mark P.
AU - Alfred Witjes, J.
AU - Kiemeney, Lambertus A.
N1 - Funding Information:
We would like to thank all urologists who were willing to cooperate in this study, as well as all participants. The Comprehensive Cancer Centres East and South provided the data. We used the program package S.A.G.E., which is supported by a U.S. Public Health Service Resource Grant (1 P41 RR03655) from the National Centre for Research Resources. This work was supported by grant #KUN 96-1339 from the Dutch Cancer Society. Dr. Baffoe-Bonnie received support from USPHS grant CA-06927 and an appropriation from the Commonwealth of Pennsylvania.
PY - 2006/7
Y1 - 2006/7
N2 - 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.
AB - 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.
KW - Familial aggregation
KW - Segregation analysis
KW - Urothelial cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=33745132759&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745132759&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2005.07.039
DO - 10.1016/j.ejca.2005.07.039
M3 - Article
C2 - 16737809
AN - SCOPUS:33745132759
SN - 0959-8049
VL - 42
SP - 1428
EP - 1433
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 10
ER -