ZIA CP010222-10490 (ZIA) | |||
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Title | Molecular and Histopathologic Clues to the Understanding of Thyroid Cancer Incide | ||
Institution | NCI, Bethesda, Ma | ||
Principal Investigator | Sigurdson, Alice | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $422,317 | Project Dates | 01/01/2009 - N/A |
Fiscal Year | 2011 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Biochemical Epidemiology (45.0%) Cancer (100.0%) |
Thyroid (100.0%) | ||
Research Type | |||
Cancer Related Biology Exogenous Factors in the Origin and Cause of Cancer |
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Abstract | |||
Thyroid cancer incidence has increased significantly over the last few decades. In the United States, the incidence rates have nearly tripled from 1973 to 2005. This rise has been attributed primarily to small papillary thyroid carcinomas, which suggests that better surveillance by ultrasound, which enables detection of small thyroid tumors, is the main reason for the increase. However, new data demonstrating increases in larger tumors indicate that better detection cannot entirely explain the increase. The molecular pathogenesis of papillary thyroid carcinomas involves RET/PTC rearrangements, and BRAF and RAS mutations. These genetic alterations rarely overlap in the same tumor and together they occur in 70-80% of papillary carcinomas. RET/PTC chromosomal rearrangements often are associated with a history of radiation exposure, whereas the genetic alterations involving BRAF and RAS are point mutations and have a different etiology more characteristic of chemical carcinogenesis or oxidative damage. The BRAF mutation is associated with more aggressive clinical behavior of papillary carcinomas. While the prevalence of BRAF mutations is consistently found in 40-45% of tumors, the prevalence of RET/PTC is highly variable by geographic location. It remains unclear whether the prevalence of these mutations or the frequency of different histopathologic variants of papillary carcinoma have changed over time. We propose to perform a detailed comparative tumor analysis of molecular alterations and histopathology of papillary carcinomas currently treated and those removed surgically more than 30 years ago. This approach may provide important clues to the reasons for the increase in the incidence of thyroid cancer. |