radiation dose with some evidence of nonlinearity in the dose-response, but with no evidence of an interaction with ultraviolet radiation. No dose-response association was found for squamous cell carcinoma (69 cases). The relationships with dose for melanoma (10 cases) and Bowen’s disease (26 cases) were not statistically significant, but estimates of the ERR/Sv were large.

Central Nervous System Cancers

See discussion of central nervous system tumors at the end of the section “Benign Neoplasms.”

Lymphoma

Analyses of mortality data by Pierce and colleagues (1996) showed no evidence of an association for lymphoma; with the mortality data, it was not possible to distinguish between Hodgkin’s and non-Hodgkin’s cases. Lymphoma was not included in more recent mortality analyses. The incidence data included 210 lymphoma cases, of which 22 were Hodgkin’s and 188 were non-Hodgkin’s. A statistically significant dose-response was found for males, but not for females, for whom the estimated ERR/Sv was negative (Preston and others 1994).

Multiple Myeloma

Multiple myeloma exhibited a statistically significant dose-response based on the mortality data (Pierce and others 1996), but incidence data showed little evidence of such an association (Preston and others 1994). The discrepancy in these findings appears to be due to deaths with questionable diagnoses and second primary tumors that were included in the mortality analyses, but not the incidence analyses.

CANCERS RESULTING FROM EXPOSURE IN UTERO

Delongchamp and colleagues (1997) analyzed data on cancer mortality among atomic bomb survivors who were exposed either in utero or, for comparison, during the first 5 years of life. These analyses covered the period 1950–1992, adding an additional 8 years of follow-up to data available to the BEIR V committee (Yoshimoto and others 1988). Analyses were restricted to cancers occurring between the ages of 17 and 45. Ten cancers were observed in the cohort exposed in utero, and a significant dose-response was observed with an estimated ERR/Sv of 2.1 (90% CI 0.2, 6.0). This estimate did not differ significantly from that observed for survivors exposed during the first 5 years of life. An unusual aspect of the finding was that 9 of the 10 cancers occurred in females, and significant differences between the sexes persisted even when the three female cancer sites (breast, ovary, and uterus) were excluded.

BENIGN NEOPLASMS

Studies addressing benign neoplasms have generally been based on either the AHS or the tumor registries. Fujiwara and colleagues (1992) used the AHS to investigate hyperparathyroidism in Hiroshima survivors. About 4000 individuals with DS86 doses were tested for hyperparathyroidism, and a dose-response relationship was found (p < .001). The estimated relative risk at 1 Gy was 4.1 (95% CI 1.7, 14.0), and a decrease in relative risk with increasing age at exposure was suggested. The authors concluded that doses lower than those used in radiotherapy might induce this disorder. Nagataki and colleagues (1994) used Nagasaki AHS data to investigate thyroid diseases in 2587 subjects with diagnoses based on uniform procedures including ultrasonic scanning. Significant dose-response relationships were observed for all solid nodules (females), adenoma, and nodules without histological diagnosis (females). An association was also found for autoimmune hypothyroidism, one of the nonneoplastic end points investigated. However, the dose-response for hypothyroidism was not monotonic; risk increased to about 0.7 Sv and then decreased.

Ron and colleagues (1995b) used data from the Hiroshima and Nagasaki tumor and tissue registries to evaluate benign tumors of the stomach, colon, and rectum for 1958–1989. A total of 470 cases with histologically confirmed benign gastrointestinal tumors (163 stomach, 215 colon, and 92 rectum) were identified. A positive dose-response relationship was observed for stomach tumors, with an estimated ERR/Sv of 0.52 (95% CI 0.01–1.43), similar to that for stomach cancer. There was little evidence of dose-response for either colon or rectal tumors.

Tokunaga and colleagues (1993) investigated proliferative and nonproliferative breast disease using breast tissue samples from 88 high-dose and 225 low-dose autopsy cases of members of the LSS cohort. Both proliferative disease in general and atypical hyperplasia in particular were found to be positively associated with radiation dose, with the strongest association for subjects who were 40–49 years of age at exposure. The authors hypothesized that this finding might be “related to the age dependence of radiation-induced breast cancer, in that potential cancer induced in this age group by radiation exposure may receive too little hormonal promotion to progress to frank cancers.”

Kawamura and colleagues (1997) conducted a study of uterine myoma based on ultrasound examination of 1190 female AHS participants in Hiroshima. The reason for conducting this study was concern that the previously identified dose-response associations (Wong and others 1993), discussed below, might have resulted from bias in case detection. This study resulted in an estimated ERR/Sv of 0.61 (95% CI 0.12, 1.31). It was judged unlikely that bias could explain the association. In earlier analyses by Wong and colleagues, time since exposure was found to be a significant modifier for uterine myoma, with younger survivors show-



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