title: Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours.
abstract: 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.
authors.affiliation: Sections of Cancer Genetics and Molecular Carcinogenesis, Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK.
authors.forename: E A
authors.initials: EA
authors.lastname: Rapley
authors.forename: G P
authors.initials: GP
authors.lastname: Crockford
authors.forename: D
authors.initials: D
authors.lastname: Teare
authors.forename: P
authors.initials: P
authors.lastname: Biggs
authors.forename: S
authors.initials: S
authors.lastname: Seal
authors.forename: R
authors.initials: R
authors.lastname: Barfoot
authors.forename: S
authors.initials: S
authors.lastname: Edwards
authors.forename: R
authors.initials: R
authors.lastname: Hamoudi
authors.forename: K
authors.initials: K
authors.lastname: Heimdal
authors.forename: S D
authors.initials: SD
authors.lastname: Fossâ
authors.forename: K
authors.initials: K
authors.lastname: Tucker
authors.forename: J
authors.initials: J
authors.lastname: Donald
authors.forename: F
authors.initials: F
authors.lastname: Collins
authors.forename: M
authors.initials: M
authors.lastname: Friedlander
authors.forename: D
authors.initials: D
authors.lastname: Hogg
authors.forename: P
authors.initials: P
authors.lastname: Goss
authors.forename: A
authors.initials: A
authors.lastname: Heidenreich
authors.forename: W
authors.initials: W
authors.lastname: Ormiston
authors.forename: P A
authors.initials: PA
authors.lastname: Daly
authors.forename: D
authors.initials: D
authors.lastname: Forman
authors.forename: T D
authors.initials: TD
authors.lastname: Oliver
authors.forename: M
authors.initials: M
authors.lastname: Leahy
authors.forename: R
authors.initials: R
authors.lastname: Huddart
authors.forename: C S
authors.initials: CS
authors.lastname: Cooper
authors.forename: J G
authors.initials: JG
authors.lastname: Bodmer
authors.forename: D F
authors.initials: DF
authors.lastname: Easton
authors.forename: M R
authors.initials: MR
authors.lastname: Stratton
authors.forename: D T
authors.initials: DT
authors.lastname: Bishop
mesh_terms: D000293:Adolescent; D000328:Adult; D002874:Chromosome Mapping; D005190:Family; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018237:Germinoma / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008126:Lod Score; D008297:Male; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000453:epidemiology / Q000235:genetics*; D014960:X Chromosome
chemical_list: D005819:Genetic Markers