TY - JOUR
T1 - Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours
AU - Rapley, Elizabeth A.
AU - Crockford, Gillian P.
AU - Teare, Dawn
AU - Biggs, Patrick
AU - Seal, Sheila
AU - Barfoot, Rita
AU - Edwards, Sandra
AU - Hamoudi, Rifat
AU - Heimdal, Ketil
AU - Fosså, Sophie D.
AU - Tucker, Kathy
AU - Donald, Jenny
AU - Collins, Felicity
AU - Friedlander, Michael
AU - Hogg, David
AU - Goss, Paul
AU - Heidenreich, Axel
AU - Ormiston, Wilma
AU - Daly, Peter A.
AU - Forman, David
AU - Oliver, R. Timothy D.
AU - Leahy, Michael
AU - Huddart, Robert
AU - Cooper, Colin S.
AU - Bodmer, Julia G.
AU - Easton, Douglas F.
AU - Stratton, Michael R.
AU - Bishop, D. Timothy
N1 - Funding Information:
We thank the families and the clinicians, including T. Sandeman and K. Cox, for participation; J. Nicholls for collecting many of the ICR families; and E. Peacock for help in preparing the manuscript. We acknowledge the support of the Cancer Research Campaign, the New South Wales Cancer Council and the Imperial Cancer Research Fund.
PY - 2000/2
Y1 - 2000/2
N2 - Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most common cancer in males aged 15-40 in Western European populations. The incidence of TGCT has risen dramatically over the last century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, previously diagnosed TGCT (ref. 7) and a family history of the disease. Brothers of men with TGCT have an 8-10-fold risk of developing TGCT (refs 8,9), whereas the relative risk to fathers and sons is fourfold (ref. 9). This familial relative risk is much higher than that for most other types of cancer. We have collected samples from 134 families with two or more cases of TGCT, 87 of which are affected sibpairs. A genome-wide linkage search yielded a heterogeneity lod (hlod) score of 2.01 on chromosome Xq27 using all families compatible with X inheritance. We obtained a hlod score of 4.7 from families with at least one bilateral case, corresponding to a genome-wide significance level of P=0.034. The proportion of families with UDT linked to this locus was 73% compared with 26% of families without UDT (P=0.03). Our results provide evidence for a TGCT susceptibility gene on chromosome Xq27 that may also predispose to UDT.
AB - Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most common cancer in males aged 15-40 in Western European populations. The incidence of TGCT has risen dramatically over the last century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, previously diagnosed TGCT (ref. 7) and a family history of the disease. Brothers of men with TGCT have an 8-10-fold risk of developing TGCT (refs 8,9), whereas the relative risk to fathers and sons is fourfold (ref. 9). This familial relative risk is much higher than that for most other types of cancer. We have collected samples from 134 families with two or more cases of TGCT, 87 of which are affected sibpairs. A genome-wide linkage search yielded a heterogeneity lod (hlod) score of 2.01 on chromosome Xq27 using all families compatible with X inheritance. We obtained a hlod score of 4.7 from families with at least one bilateral case, corresponding to a genome-wide significance level of P=0.034. The proportion of families with UDT linked to this locus was 73% compared with 26% of families without UDT (P=0.03). Our results provide evidence for a TGCT susceptibility gene on chromosome Xq27 that may also predispose to UDT.
UR - http://www.scopus.com/inward/record.url?scp=0033961884&partnerID=8YFLogxK
U2 - 10.1038/72877
DO - 10.1038/72877
M3 - Article
C2 - 10655070
AN - SCOPUS:0033961884
VL - 24
SP - 197
EP - 200
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 2
ER -
