ZIA CP005803-10385 (ZIA) | |||
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Title | Genetic Epidemiology | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | M Goldstein, Alisa | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $57,291 | Project Dates | 11/01/2004 - N/A |
Fiscal Year | 2009 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) |
Urinary System (100.0%) | ||
Research Type | |||
Normal Functioning Resources and Infrastructure Related to Etiology |
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Abstract | |||
Renal cancer rates in Central Europe are among the highest in the world. The von Hippel Lindau-Hypoxia Inducible Factor (VHL-HIF) pathway plays a critical role in the development of kidney cancer. This study has two major objectives. First, to perform a haplotype-based study in the Central European Renal Cell Cancer (CERCC) Case-Control Study to investigate whether haplotype variations in five genes in the VHL-HIF pathway are associated with the susceptibility to kidney cancer. Second, we plan to determine if particular occupational exposures are associated with somatic genetic alterations in genes associated with RCC. In our preliminary studies, we surveyed single nucleotide polymorphisms (SNPs) across the genomic regions of five genes [VHL (3p25), HIF1A (14q23), HIF2A (2p21), EGLN3 (14q13) and FH (1q43)] involved in the VHL-HIF pathway covering an average of 15 kb upstream and downstream. In our proposed studies, we plan to genotype these 44 SNPs in the samples from the CERCC Case-Control Study. In a parallel investigation, we also plan to screen RCC tumors for loss of heterozygosity (LOH) in 21 genes, and mutations in the Birt-Hogg-Dube (BHD) and fumarate hydratase (FH) gene. We also plan to test whether LOH or mutations in specific genes correlate with RCC staging. Finally, we will determine if particular occupational exposures and lifestyle factors are associated with LOH and/or specific mutations. |