title: Analysis of dose response for circulatory disease after radiotherapy for benign disease.
abstract: OBJECTIVE
  To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure.
  
  
  METHODS
  This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease).
  
  
  RESULTS
  There were significant excess risks for all circulatory disease, with an excess relative risk Gy(-1) of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy(-1) of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups.
  
  
  CONCLUSIONS
  There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.
authors.affiliation: Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland, USA. mark.little@nih.gov
authors.forename: Mark P
authors.initials: MP
authors.lastname: Little
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Kleinerman
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Susan A
authors.initials: SA
authors.lastname: Smith
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Mabuchi
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001921:Brain / Q000528:radiation effects; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000401:mortality; D015331:Cohort Studies; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006321:Heart / Q000528:radiation effects; D006801:Humans; D007564:Japan; D007668:Kidney / Q000528:radiation effects; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000209:etiology; D016273:Occupational Exposure / Q000009:adverse effects; D058958:Organs at Risk / Q000528:radiation effects; D010179:Pancreas / Q000528:radiation effects; D010437:Peptic Ulcer / Q000532:radiotherapy*; D019047:Phantoms, Imaging; D011847:Radioactive Fallout / Q000009:adverse effects; D011878:Radiotherapy / Q000009:adverse effects; D012306:Risk; D020521:Stroke / Q000209:etiology; D017741:Survivors; D013961:Thyroid Gland / Q000528:radiation effects; D013997:Time Factors
chemical_list: D011847:Radioactive Fallout