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 | $257,798 | Project Dates | 06/01/2000 - 00/00/0000 |
Fiscal Year | 2015 | 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. 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 16 new GWAS susceptibility loci; (e) documenting a 50-fold risk stratification using a polygenic risk score plus cryptorchidism; (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. |