A large proportion of the U.S. population comes into contact with small doses of ionizing radiation through occupational exposures or from background ionizing radiation. More recently, an additional and increasing source of radiation exposure is from medical diagnostic radiation examinations, such as X-rays and computed tomography (CT) scans. While the risk of leukemia from high doses of ionizing radiation are well known, the risk of other hematologic cancers, such as multiple myeloma (MM) or non-Hodgkin lymphoma (NHL), are not well understood. Neither are the risks from lower radiation doses that are protracted over time. We propose to examine the association between diagnostic X-rays and hematologic cancer outcomes by pooling the data from a large Canadian Fluoroscopy cohort study with data from a similar study in Massachusetts, conducted by the Radiation Epidemiology Branch of the Division of Cancer Epidemiology and Genetics, the National Cancer Institute (NCI). Fluoroscopy is an imaging technique that uses X-rays to obtain real-time moving images of patient's organs. Patients from the Canadian and NCI cohorts received repeated X-ray fluoroscopic examinations in the course of treatment for tuberculosis. Neither study has examined risks of hematologic cancers in the past. This proposed study of radiation-related risks of hematologic cancers in the pooled analysis of fluoroscopy studies (HemFluoro study) will include 77,100 patients with more than 50 years of follow up for mortality from hematologic cancers. Analyses will be based on 222 cases of leukemia, 70 cases of multiple myeloma and 183 cases of non-Hodgkin lymphoma, making it the largest study of hematologic cancers in a population exposed to low doses of diagnostic ionizing radiation. Study findings will be directly relevant for risk projections for the U.S. population exposed to CT scans because of similarity of background rates of hematologic cancers and of radiation exposures. The study sample will include men and women of a wide range of ages and additionally will have extensive data on modifiable risk factors, such as smoking. Evaluation of modifiable risk factors is one of the four key areas of research specified in the PAR-12-039 announcement. The overall scientific objective is to expand the existing body of knowledge on radiation-related risks of leukemia, MM and NHL and to address remaining gaps in knowledge with respect to radiation-related carcinogenesis at low-dose radiation exposures. Results from this study will stimulate further research on hematologic cancers in different populations. The public health impact of this study will be significant because we will assess the appropriateness of current public radiation safety limits, which are primarily based on the studies of subjects exposed to high doses of ionizing radiation.