A reanalysis of curvature in the dose response for cancer and modifications by age at exposure following radiation therapy for benign disease.
OBJECTIVE
To assess the shape of the dose response for various cancer endpoints and modifiers by age and time.


METHODS
Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other).


RESULTS
There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy(-1) of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers.


CONCLUSIONS
There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.
Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland 20852-7238, USA. mark.little@nih.gov
Mark P
MP
Little
Marilyn
M
Stovall
Susan A
SA
Smith
Ruth A
RA
Kleinerman
D000328:Adult; D000367:Age Factors; D000368:Aged; D016001:Confidence Intervals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007953:Leukemia, Radiation-Induced / Q000209:etiology / Q000401:mortality; D016014:Linear Models; D008175:Lung Neoplasms / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000401:mortality; D010190:Pancreatic Neoplasms / Q000209:etiology / Q000401:mortality; D010437:Peptic Ulcer / Q000532:radiotherapy*; D011847:Radioactive Fallout / Q000009:adverse effects; D012306:Risk; D013274:Stomach Neoplasms / Q000209:etiology / Q000401:mortality; D013997:Time Factors
D011847:Radioactive Fallout