ZIA CP010144 - 07070 (ZIA) | |||
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Title | Clinical and genetic studies of familial testicular cancer | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Loud, Jennifer | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $368,480 | Project Dates | 06/01/2000 - 00/00/0000 |
Fiscal Year | 2014 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Basic Behavioral and Social Science (25.0%) Biochemical Epidemiology (45.0%) Cancer (100.0%) |
Testes (100.0%) | ||
Research Type | |||
Cancer-Related Biology Endogenous Factors in the Origin and Cause of Cancer |
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Abstract | |||
This is a multidisciplinary etiologic study targeting families at increased risk of testicular cancer (FTGCT). The goals of this study include: (1) define the clinical phenotype of familial TC; (2) map and clone hereditary TGCT susceptibility genes; (3) determine if cancers other than TGCT are part of the FTGCT syndrome; (4) determine if the pathology of FTGCT differs from that of non-familial TC; and (5) create a biospecimen repository for subsequent translational research projects. Recent findings to date include (a) excluding the presence of a dysmorphic phenotype in TC families; (b) excluding the presence of developmental anomalies of the GU system as a component of the familial TC phenotype; (c) demonstrating that promoter methylation of GWAS-identified TGCT susceptibility genes may play a role in FTGCT susceptibility; (d) confirming recent GWAS findings by showing that variants in or near KITLG, BAK1, DMRT1 and TERT-CLPTM1L ( predispose to FTGCT, plus contributing to the identification of 5 new GWAS susceptibility loci; (e) described an association between FTGCT and in utero DES exposure; (f) determining that FTGCT is a cancer site-specific syndrome; (g) presenting the first prospective FTGCT risk analysis, which revealed a 12-fold increase in TGCT risk among high-risk family members; and (h) demonstrating that the CEGRM genetic counseling tool works as well in male as in female subjects. We leverage state-of-the-science genomic tools (whole exome and whole genome sequencing, CGH array, fine-mapping, CNV evaluation, somatic genetics, studies of twins discordant for TGCT, genotyping GWAS risk SNPs in persons with UDT, infertility to purse a more detailed understanding of TGCT genetics and to refine TGCT risk stratification. We continue to investigate the relationship between testicular microlithiasis and FTGCT risk that we reported on several years ago. " |