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This Article Full Text Full Text (PDF) All Versions of this Article: ERC-09-0254v1 17/2/R109    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Greene, M. H Articles by Korde, L. A PubMed PubMed Citation Articles by Greene, M. H Articles by Korde, L. A

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20852, USA
¹ Urologic Oncology Branch, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland 20852, USA
² Diagnostic Radiology Department, National Institutes of Health, Warren G. Magnuson Clinical Center, Bethesda, Maryland 20892, USA
³ Molecular Imaging Program, National Cancer Institute, Bethesda, Maryland 20852, USA
⁴ Westat, Inc., 6116 Executive Boulevard, Suite 400, Rockville, Maryland, USA
⁵ Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20852, USA

(Correspondence should be addressed to M H Greene; Email: greenem{at}mail.nih.gov)

Familial aggregations of testicular germ cell tumor (FTGCT) have been well described, suggesting the existence of a hereditary TGCT subset. Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four- to sixfold and eight- to tenfold increases in TGCT risk respectively. Segregation analyses suggest an autosomal recessive mode of inheritance. Linkage analyses have identified several genomic regions of modest interest, although no high-penetrance cancer susceptibility gene has been mapped yet. These data suggest that the combined effects of multiple common alleles, each conferring modest risk, might underlie familial testicular cancer. Families display a mild phenotype: the most common number of affected families is 2. Age at diagnosis is 2-3 years younger for familial versus sporadic cases. The ratio of familial seminoma to nonseminoma is 1.0. FTGCT is more likely to be bilateral than sporadic TGCT. This syndrome is cancer site specific. Testicular microlithiasis is a newly recognized FTGCT component. Candidate gene-association studies have implicated the Y chromosome gr/gr deletion and PDE11A gene mutations as genetic modifiers of FTGCT risk. Two genomewide association studies of predominantly sporadic but also familial cases of TGCT have implicated the KIT-ligand, SPRY4, and BAK1 genes as TGCT risk modifiers. All five loci are involved in normal testicular development and/or male infertility. These genetic data provide a novel insight into the genetic basis of FTGCT, and an invaluable guide to future TGCT research.