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Grant Details

Grant Number: 3R01CA102042-05S1 Interpret this number
Primary Investigator: Cortessis, Victoria
Organization: University Of Southern California
Project Title: A Genetic Linkage Study of Testicular Cancer
Fiscal Year: 2009
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Abstract

DESCRIPTION (provided by applicant): Testicular cancer is a disease of very young men. Until recently, it was the leading cancer among men aged 15-29, and it is now second only to the AIDS-related neoplasm, Kaposi's sarcoma. Although survival has improved, young men still die from this neoplasm, and many survivors live most of their adult years with very undesirable consequences of their disease. The steady rise in incidence of this group of tumors needs to be explained, and is made all the more alarming by the possibility that the set of factors responsible for increasing incidence rates of testicular cancer may also be causing a poorly measured increase in the prevalence of various urogenital malformations in male infants. The two established risk factors are family history of testis cancer (relative risk of 10 for brothers) and a personal history of cryptorchidism or congenitally undescended testicles (relative risk 2.5-18). Familial risk, segregation analysis and preliminary linkage analyses suggest that major susceptibility genes predispose to testis cancer and possibly to the antecedent condition cryptorchidism. Linkage analysis of 180 families conducted by the International Testis Cancer Linkage Consortium (ITCLC) identified a region of Xq27 with significant evidence for linkage, with a pattern of occurrence suggesting that a gene in the region, TGCT1, confers risk of both testis cancer and cryptorchidism. We have identified and partially enrolled a population- based sample of 301 multiple case families informative for genetic linkage analysis of testis cancer and cryptorchidism. To search for major susceptibility genes, we propose to complete enrollment of a full set of 497 such families; contribute to the ongoing effort to clone TGCT; and conduct a two-stage genome scan among this series of 497 families in which we will collaborate with the ITCLC both to identify regions to be studied in the second, fine mapping stage, and to implement fine mapping efforts. The 497 enrolled families will be the largest set of informative families assembled, and this research should substantially accelerate discovery of genes predisposing to these conditions. Because this is a population-based study, the resource assembled in the proposed research will be appropriate for immediate gene characterization upon identification and cloning of major susceptibility genes for these conditions.

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Publications

Null association between histology of first and second primary malignancies in men with bilateral testicular germ cell tumors.
Authors: Thomas JP, Davis-Dao C, Lewinger JP, Siegmund KD, Hamilton AS, Daneshmand S, Skinner EC, Thomas DC, Cortessis VK
Source: Am J Epidemiol, 2013 Oct 15;178(8), p. 1240-5.
EPub date: 2013 Aug 8.
PMID: 23928263
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Meta-analysis identifies four new loci associated with testicular germ cell tumor.
Authors: Chung CC, Kanetsky PA, Wang Z, Hildebrandt MA, Koster R, Skotheim RI, Kratz CP, Turnbull C, Cortessis VK, Bakken AC, Bishop DT, Cook MB, Erickson RL, Fosså SD, Jacobs KB, Korde LA, Kraggerud SM, Lothe RA, Loud JT, Rahman N, Skinner EC, Thomas DC, Wu X, Yeager M, Schumacher FR, Greene MH, Schwartz SM, McGlynn KA, Chanock SJ, Nathanson KL
Source: Nat Genet, 2013 Jun;45(6), p. 680-5.
EPub date: 2013 May 12.
PMID: 23666239
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Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23.
Authors: Schumacher FR, Wang Z, Skotheim RI, Koster R, Chung CC, Hildebrandt MA, Kratz CP, Bakken AC, Bishop DT, Cook MB, Erickson RL, Fosså SD, Greene MH, Jacobs KB, Kanetsky PA, Kolonel LN, Loud JT, Korde LA, Le Marchand L, Lewinger JP, Lothe RA, Pike MC, Rahman N, Rubertone MV, Schwartz SM, Siegmund KD, Skinner EC, Turnbull C, Van Den Berg DJ, Wu X, Yeager M, Nathanson KL, Chanock SJ, Cortessis VK, McGlynn KA
Source: Hum Mol Genet, 2013 Jul 1;22(13), p. 2748-53.
EPub date: 2013 Mar 5.
PMID: 23462292
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Potential impact of age at first marijuana use on the development of nonseminomatous testicular germ cell tumors.
Authors: Lacson JC, Bernstein L, Cortessis VK
Source: Cancer, 2013 Mar 15;119(6), p. 1284-5.
EPub date: 2012 Dec 11.
PMID: 23233189
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Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk.
Authors: Lacson JC, Carroll JD, Tuazon E, Castelao EJ, Bernstein L, Cortessis VK
Source: Cancer, 2012 Nov 1;118(21), p. 5374-83.
EPub date: 2012 Sep 10.
PMID: 22965656
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Heterogenous effect of androgen receptor CAG tract length on testicular germ cell tumor risk: shorter repeats associated with seminoma but not other histologic types.
Authors: Davis-Dao CA, Siegmund KD, Vandenberg DJ, Skinner EC, Coetzee GA, Thomas DC, Pike MC, Cortessis VK
Source: Carcinogenesis, 2011 Aug;32(8), p. 1238-43.
EPub date: 2011 Jun 3.
PMID: 21642359
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Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors.
Authors: Linger R, Dudakia D, Huddart R, Tucker K, Friedlander M, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Chompret A, Stoppa-Lyonnet D, Bonaïti-Pellié C, Heidenreich A, Albers P, Olah E, Geczi L, Bodrogi I, Daly PA, Guilford P, Fosså SD, Heimdal K, Tjulandin SA, Liubchenko L, Stoll H, Weber W, Einhorn L, McMaster M, Korde L, Greene MH, Nathanson KL, Cortessis V, Easton DF, Bishop DT, Stratton MR, Rapley EA
Source: Genes Chromosomes Cancer, 2008 Mar;47(3), p. 247-52.
PMID: 18069663
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Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis.
Authors: Davis-Dao CA, Tuazon ED, Sokol RZ, Cortessis VK
Source: J Clin Endocrinol Metab, 2007 Nov;92(11), p. 4319-26.
EPub date: 2007 Aug 7.
PMID: 17684052
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Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.
Authors: Crockford GP, Linger R, Hockley S, Dudakia D, Johnson L, Huddart R, Tucker K, Friedlander M, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Chompret A, Bonaïti-Pellié C, Heidenreich A, Albers P, Olah E, Geczi L, Bodrogi I, Ormiston WJ, Daly PA, Guilford P, Fosså SD, Heimdal K, Tjulandin SA, Liubchenko L, Stoll H, Weber W, Forman D, Oliver T, Einhorn L, McMaster M, Kramer J, Greene MH, Weber BL, Nathanson KL, Cortessis V, Easton DF, Bishop DT, Stratton MR, Rapley EA
Source: Hum Mol Genet, 2006 Feb 1;15(3), p. 443-51.
EPub date: 2006 Jan 11.
PMID: 16407372
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