ZIA CP005782-10790 (ZIA) | |||
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Title | Studies of metastatic cancer | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | O'Brien, Thomas | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $27,019 | Project Dates | 00/00/0000 - 00/00/0000 |
Fiscal Year | 2017 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) Interferon (100.0%) Metastasis (100.0%) |
Colon/Rectum (50.0%) Ovarian Cancer (50.0%) |
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Research Type | |||
Cancer Progression & Metastasis Interactions of Genes and/or Genetic Polymorphisms with Exogenous and/or Endogenous Factors |
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Abstract | |||
"The permeability of tissue barriers could, play a role in metastatic cancer. Recent work has shown that IFN-s can control the integrity of epithelial and endothelial barriers. All humans produce IFN-1, IFN-2 and IFN-3, but IFN-4 is unusual in that it is restricted by the IFNL4- G/TT (rs368234815) frameshift genetic variant. The IFNL4- G allele creates the open reading frame for the full-length IFN-4 protein, whereas the alternative allele (IFNL4-TT) does not generate IFN-4. IFN-4 is produced only by individuals who carry at least one copy of the IFNL4- G allele. Dr. Ronnett and her colleagues found that among 52 mucinous carcinomas located in the ovaries, careful pathological review revealed that 40 (77%) were actually metastatic from other sites, with 45% of the metastatic carcinomas originating in the gastrointestinal tract. A recent GWAS for MOC found the strongest association for a variant that marks IFNL4- G/TT, with the protein generating IFNL4- G being protective. However, because of the difficulty in differentiating primary from metastatic mucinous ovarian carcinoma, Dr. Ronnett and Dr. Sherman, internationally recognized gynecological pathologists collaborating with us on the current proposal, believe that many of the cases included in that GWAS might actually have been tumors that had metastasized to the ovary. Thus, combining the GWAS finding with evidence that IFNs enhance barrier integrity generates the hypothesis that the IFNL4- G allele (and IFN4 protein) could protect against metastases to the ovary. This pilot effort will assess our ability to: Identify subjects with mucinous carcinomas that had metastasized to the ovary. Collect basic clinical and demographic data from the medical records of these patients. Retrieve formalin-fixed paraffin-embedded (FFPE) tissue blocks from these patients. DNA from the blocks of sufficient quality to allow genotyping for the IFNL4- G/TT variant. " |