ALTE03N1: Key Adverse Events Following Childhood Cancer
There has been a plethora of reports describing late effects among survivors of childhood cancer, and identifying demographic and treatment-related risk factors. However, very little attention has been given to the genetic susceptibility of the individuals at risk for developing these complications. We propose to develop a mechanism to identify genetic risk factors among survivors of childhood cancer who develop key adverse events. The overall goal of this study is to identify polymorphisms in candidate genes that confer susceptibility to the key adverse events developing among these survivors. These key adverse events were selected because of at least one of the following characteristics: 1) relatively high incidence of the key adverse events anticipated among childhood cancer survivors, 2) clear epidemiological association with therapy given for the primary malignancy, 3) chronic nature of adverse events, hence a significant impact on the overall functioning and QOL of survivors, 4) high morbidity and mortality associated with occurrences of the key adverse events. The goal of the present proposal is to characterize the key adverse events in patients who have undergone therapy for childhood cancer, and to establish a mechanism for maintaining a repository of patient DNA and RNA. This resource will provide identification of patients of particular interest for polymorphisms in candidate genes involved in the pathogenesis of key adverse events, and hence an opportunity to explore the evidence for gene-environment interactions. Intrinsic to this proposal is the use of biological samples for the following overarching goals: 1) identification of genetic risk factors associated with the development of the key events, 2) examination of the interaction between genetic susceptibility and environment (cancer therapy), 3) provide the foundation for investigation of the molecular mechanisms of the events of interest.
This study will facilitate the identification of and amp;quot;high-risk and amp;quot; groups, thus allowing for risk prediction and implementation of both primary prevention strategies (individualizing future therapy to reduce the incidence of adverse events) and secondary prevention strategies (recommending screening guidelines, behavior modifications, and specific interventions) in order to reduce morbidity in high-risk groups. This proposal from COG therefore represents an excellent opportunity to investigate the role of genetic susceptibility factors as determinants of risk for key late-occurring adverse effects of childhood cancer therapy. The proposed strategy, utilizing a case-control study design, represents an approach that is feasible and will be highly efficient within the cooperative group setting. The study involves obtaining 8.5 ml (about 2 teaspoons) of blood from each patient. Blood drawing may occasionally cause pain, bruising, bleeding, or infection at the site of the needle stick. Care will be taken to avoid these complications. For patients not able to give blood cheek cells will be collected by spitting siliva into a collection disc or twirling a brush on the inside of the cheek. They will receive a kit with instructions on how to collect the cells. The entire kit will be mailed back to the laboratory using the return mailing labels and postage provided. Patients will also be asked to complete a brief questionnaire detailing their family history and health history. The patient and amp;apos;s medical records will be reviewed by the researchers. The questionnaire should take about 10-15 minutes to complete. Additional health information will be collected by looking at their child and amp;apos;s medical chart. This information will be used to study how individual family, health, and treatment history might be related with a greater risk of late-occurring complications. The nature of the study may trigger questions or identify sensitive topics of concern, so support and counseling will be available if needed.
Cases will consist of patients experiencing one or more key adverse events, who meet the following criteria:
1. Diagnosis of primary cancer at age 21 or younger, irrespective of current age;
2. No prior history of allogeneic (non-autologous) hematopoietic cell transplant;
3. Development of one of the following key adverse events at any time following initiation of cancer therapy: Cardiac dysfunction (both symptomatic and asymptomatic), ischemic stroke, subsequent malignant neoplasm, or avascular necrosis;
4. Written informed consent from the patient and/or the patient's legally authorized guardian, obtained in accordance with institutional policies approved by the U.S. Department of Health and Human Services;
5. Submission of a blood specimen (or in certain cases a buccal cell specimen);
6. In active follow up by a COG institution.
Upon receipt of the case registration information by the COG Operations Office, controls will be identified following the above inclusion criteria with the exception of the presence of a Key Adverse Event.