Prediction Model for Radiation Sensitivity in Children with Cancer

癌症儿童辐射敏感性预测模型

基本信息

批准号：
7641844
负责人：
Stella Margaret Davies
金额：
$ 22.59万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-16 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7641844
关键词：
21 year old Address Adolescent Adverse effects Age Basal cell carcinoma Biological Markers Bone Marrow Transplantation Cancer Survivor Candidate Disease Gene Carcinoma Child Childhood Cancer Survivor Study Code Cohort Studies Cytotoxic Chemotherapy DNA DNA Repair DNA Repair Gene DNA Repair Pathway Data Data Set Development Diagnosis Dose Epidemiology Exposure to Follow-Up Studies Frequencies Future General Population Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genotype Grant Health Hematologic Neoplasms Incidence Individual Investigation Investigator-Initiated Research Ionizing radiation Late Effects Long-Term Survivors Low Dose Radiation Malignant Childhood Neoplasm Malignant Neoplasms Modeling Organ Outcome Participant Pathway interactions Patients Persons Population Predisposition Radiation Radiation Tolerance Radiation therapy Recording of previous events Reporting Request for Proposals Research Project Grants Resources Risk Risk Factors Second Primary Neoplasms Single Nucleotide Polymorphism Site Skin Cancer Solid Sun Exposure Survivors Testing Therapeutic Time Treatment Protocols Variant Whole-Body Irradiation Work age difference base cancer radiation therapy cancer risk carcinogenesis case control childhood cancer survivor cohort experience gene environment interaction genetic profiling genetic risk factor high risk member outcome forecast peer public health relevance repaired response skin color validation studies

项目摘要

DESCRIPTION (provided by applicant): Survivors of childhood cancer have an increased risk of subsequent malignancy at another site. Previous studies in the Childhood Cancer Survivor Study (CCSS) have shown that the most frequent second malignant neoplasm is basal cell carcinoma (BCC), and that the most significant risk factor for BCC is exposure to therapeutic radiation. These data contrast with incident cases of BCC in the general population, for which the key risk factors are sun exposure and skin color. While it is clear that therapeutic radiation exposure increases risk of BCC in childhood cancer survivors, many are exposed to radiation and do not develop BCC. Thus, to address this inter- individual variation, given common exposures, we hypothesize that biomarkers of genetic susceptibility to BCC as a second malignancy will differ from those reported for incident cases. Furthermore, the occurrence of BCCs in childhood cancer survivors is potentially a marker of persons with increased radiation sensitivity. In this study, we will use a candidate gene approach in a case-control comparison to explore potential biomarkers that predict risk of BCC in childhood cancer survivors. We will validate positive observations from this investigation in two follow-up studies, which examine BCC in radiation technologists and bone marrow transplant survivors, to determine the generalizability of our observations. These validation studies are outside the work scope of this grant but will be key to the application of this approach to broader populations. We have selected a candidate gene approach for this study because the strong epidemiological data implicating ionizing radiation as the primary risk factor supports a hypothesis-driven approach to candidate gene selection. PUBLIC HEALTH RELEVANCE: Childhood cancer survivors have a high risk of developing basal cell carcinoma (BCC), a type of skin cancer, as a long-term side effect of radiation treatment. Some survivors may be genetically susceptible to developing BCC after receiving radiation treatment for their initial cancer. For this research project, we will develop a prediction model, using genetics and treatment history, to potentially help doctors tailor each patient's therapy to minimize radiation if the child has an innate susceptibility to radiation-induced BCC.

描述（由申请人提供）：儿童癌症的幸存者在另一个地点有随后的恶性肿瘤风险增加。儿童癌症幸存者研究（CCSS）先前的研究表明，最常见的第二次恶性肿瘤是基础细胞癌（BCC），而BCC最重要的危险因素是暴露于治疗辐射。这些数据与普通人群中BCC的事件案例形成鲜明对比，其中关键危险因素是暴露和肤色。虽然很明显，治疗辐射暴露会增加儿童癌症幸存者中BCC的风险，但许多人暴露于辐射，并且不发展BCC。因此，为了解决这种相互差异，鉴于常见的暴露，我们假设对BCC遗传易感性的生物标志物作为第二种恶性肿瘤将与事件病例报告的生物标志物不同。此外，BCC在儿童期癌症幸存者中的发生可能是辐射敏感性提高的人的标志。在这项研究中，我们将在病例对照比较中使用候选基因方法来探索预测儿童癌症幸存者中BCC风险的潜在生物标志物。我们将在两项后续研究中验证这项研究的积极观察结果，这些研究研究了辐射技术人员和骨髓移植幸存者中的BCC，以确定我们的观察结果的普遍性。这些验证研究超出了这笔赠款的工作范围，但对于将这种方法应用于更广泛的人群的关键。我们选择了这项研究的候选基因方法，因为强大的流行病学数据暗示电离辐射作为主要危险因素支持假设驱动的候选基因选择方法。公共卫生相关性：儿童癌症幸存者患上基底细胞癌（BCC）（一种皮肤癌）的高风险，是放射治疗的长期副作用。一些幸存者在接受其初始癌症的放射治疗后可能会在遗传上易于发展BCC。对于该研究项目，我们将使用遗传学和治疗史建立一个预测模型，以帮助医生量身定制每个患者的治疗，以最大程度地减少孩子对辐射引起的BCC的敏感性，以最大程度地减少辐射。