Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours

Elizabeth A. Rapley; Gillian P. Crockford; Dawn Teare; Patrick Biggs; Sheila Seal; Rita Barfoot; Sandra Edwards; Rifat Hamoudi; Ketil Heimdal; Sophie D. Fosså; Kathy Tucker; Jenny Donald; Felicity Collins; Michael Friedlander; David Hogg; Paul Goss; Axel Heidenreich; Wilma Ormiston; Peter A. Daly; David Forman; R. Timothy D Oliver; Michael Leahy; Robert Huddart; Colin S. Cooper; Julia G. Bodmer; Douglas F. Easton; Michael R. Stratton; D. Timothy Bishop

doi:10.1038/72877

Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours

Elizabeth A. Rapley, Gillian P. Crockford, Dawn Teare, Patrick Biggs, Sheila Seal, Rita Barfoot, Sandra Edwards, Rifat Hamoudi, Ketil Heimdal, Sophie D. Fosså, Kathy Tucker, Jenny Donald, Felicity Collins, Michael Friedlander, David Hogg, Paul Goss, Axel Heidenreich, Wilma Ormiston, Peter A. Daly, David FormanR. Timothy D Oliver, Michael Leahy, Robert Huddart, Colin S. Cooper, Julia G. Bodmer, Douglas F. Easton, Michael R. Stratton^*, D. Timothy Bishop

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

223 Citations (Scopus)

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.

Original language	English
Pages (from-to)	197-200
Number of pages	4
Journal	Nature Genetics
Volume	24
Issue number	2
DOIs	https://doi.org/10.1038/72877
Publication status	Published - Feb 2000

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Rapley, E. A., Crockford, G. P., Teare, D., Biggs, P., Seal, S., Barfoot, R., Edwards, S., Hamoudi, R., Heimdal, K., Fosså, S. D., Tucker, K., Donald, J., Collins, F., Friedlander, M., Hogg, D., Goss, P., Heidenreich, A., Ormiston, W., Daly, P. A., ... Bishop, D. T. (2000). Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours. Nature Genetics, 24(2), 197-200. https://doi.org/10.1038/72877

@article{a4ddf7e13692404b9df511960c8a04de,

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.",

author = "Rapley, {Elizabeth A.} and Crockford, {Gillian P.} and Dawn Teare and Patrick Biggs and Sheila Seal and Rita Barfoot and Sandra Edwards and Rifat Hamoudi and Ketil Heimdal and Foss{\aa}, {Sophie D.} and Kathy Tucker and Jenny Donald and Felicity Collins and Michael Friedlander and David Hogg and Paul Goss and Axel Heidenreich and Wilma Ormiston and Daly, {Peter A.} and David Forman and Oliver, {R. Timothy D} and Michael Leahy and Robert Huddart and Cooper, {Colin S.} and Bodmer, {Julia G.} and Easton, {Douglas F.} and Stratton, {Michael R.} and Bishop, {D. Timothy}",

year = "2000",

month = feb,

doi = "10.1038/72877",

language = "English",

volume = "24",

pages = "197--200",

journal = "Nature Genetics",

issn = "1061-4036",

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Rapley, EA, Crockford, GP, Teare, D, Biggs, P, Seal, S, Barfoot, R, Edwards, S, Hamoudi, R, Heimdal, K, Fosså, SD, Tucker, K, Donald, J, Collins, F, Friedlander, M, Hogg, D, Goss, P, Heidenreich, A, Ormiston, W, Daly, PA, Forman, D, Oliver, RTD, Leahy, M, Huddart, R, Cooper, CS, Bodmer, JG, Easton, DF, Stratton, MR & Bishop, DT 2000, 'Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours', Nature Genetics, vol. 24, no. 2, pp. 197-200. https://doi.org/10.1038/72877

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

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.

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U2 - 10.1038/72877

DO - 10.1038/72877

M3 - Article

C2 - 10655070

AN - SCOPUS:0033961884

SN - 1061-4036

VL - 24

SP - 197

EP - 200

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours

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