Thyroid cancer (TC) is the most common endocrine-related malignancy. In 2012, 56,460 new TC cases are expected to be diagnosed; with women diagnosed three times more often than men. To find possible trends and causes of TC, the significance of suspected risk factors that affect TC development, progression, and outcomes of clinical treatment need to be assessed and analyzed. Such studies require both the collection of the comprehensive data on TC patients and high-risk subjects as well as the establishment of a close information partnership between multiple centers across the country with expertise in TC epidemiology, genetics, biology, early detection and patient care. The design and implementation of an advanced biomedical informatics system for collecting and processing TC-related data in a standardized and efficient way is essential to promote successful TC-related research studies. The main goal of this application is to redesign the Thyroid Tumor and Cancer Collaborative Registry (TCCR), developed and maintained by the PIs, to satisfy modern requirements and best practices for data sharing, mining, and systems interoperability, including those established by the caBIG(R) community. This goal will be achieved by accomplishing the following specific aims: (i) to develop the TCCR v.2 metadata consistent with national and international standards and harmonized with the Cancer Data Standards Registry and Repository (caDSR); (ii) to develop the TCCR v.2 as a metadata- driven system; and (iii) to test, evaluate, support, and disseminate the TCCR v.2. The proposed modifications will make the TCCR v.2: (i) semantically and syntactically interoperable with other related data sources; (ii) easily upgradeable and repairable; and (iii) compliant with standards for data collection, access, mining, management, and sharing. In addition, authorized end-users and third-party applications will be able to use the application programming interfaces (APIs) developed in this project to access collected data in a standardized way suitable for data mining. Integration with the caTissue Suite will significantly expand the registry's capabilities, allowing researchers to manage and mine biospecimen data for subjects enrolled in the TCCR v.2. Multiple centers with expertise in TC epidemiology, genetics, biology, early detection, and patient care will be able to collaborate using the TCCR v.2 as a platform for the cohort and population studies. The TCCR v.2 will serve as a resource for estimating TC risk factors, predicting survivorship, aiding in treatment, evaluating quality of life of the TC patients, etc. This R03 grant applicatio is submitted as a response to FOA PAR-12-144, issued by NCI, which is aimed at developing new research methodology and technology. The technologies and procedures to be developed in this project will be reusable in other applications dealing with collection, integration and analysis of cancer- and health-related data.