compared to the general population) and among women over 55 years at irradiation (SMR 5.8; 95% CI 2.5, 11.3). The average ERR in this study was 0.19 Gy−1 (95% CI 0.08, 0.32) for intrauterine 226Ra exposure, and the average absolute excess mortality from leukemia was 2.6 per 104 PY per gray.

The risk of leukemia, lymphoma, and multiple myeloma was studied in an expanded cohort of 12,955 women treated for benign gynecological disorders at one of 17 hospitals in Massachusetts, Connecticut, Rhode Island, or New York State between 1925 and 1965 (Inskip and others 1993). Of these women, 9770 were treated with radiation (either intracavitary 226Ra or external beam X-rays), while the rest were treated by other methods. The average age at treatment was 46.5 years, and the average dose to active bone marrow in exposed women was 1.2 Gy. The RR for all cancers of hematopoietic and lymphatic tissue was 1.3 (95% CI 1.2, 1.5) for irradiated women, compared to nonirradiated. The risk of lymphomas, multiple myeloma, and nonacute lymphocytic leukemia was similar between irradiated and nonirradiated women. The RRs for acute lymphocytic leukemia and for myeloid leukemia were elevated, however: RR 3.7 (95% CI 1.3, 16) and 3.7 (95% CI 0.9, 36), respectively. For acute lymphocytic and nonlymphocytic leukemia, the SMRs were similar for women treated with radium only and with both modalities, and were smallest for X-ray patients (difference not statistically significant). The ERR per Gy was 0.29 overall; 0.37 Gy−1 (95% CI <0, 1.5) for treatment with radium only; 0.05 per Gy (95% CI −0.06, 0.33) for X-rays only; and ERR 0.21 per Gy (95% CI 0.05, 0.83) for the combination of both modalities. Average doses for the different treatment types were 0.6, 2.3, and 2.0 Gy, respectively, indicating a complex dose-response relationship.

A cohort of 2067 women who received radiotherapy for metropathia hemorrhagica (uterine bleeding disorders) in Scotland between 1940 and 1960 was followed until the end of 1990 (Darby and others 1994). The average follow-up was 28 years. Absorbed doses to the active bone marrow and to 20 solid organs or anatomical sites were estimated from treatment records. Overall, 331 deaths from cancer were observed, and significantly elevated SMRs were observed for cancers at heavily irradiated sites (average local dose >1 Gy): cancer of pelvic sites, particularly urinary bladder cancer (mean dose 5.2 Gy); colon cancer (mean dose 3.2 Gy); leukemia, and multiple myeloma (mean total active bone marrow dose 1.3 Gy). A deficit of breast cancer mortality was also observed in this cohort, due mainly to a large deficit in women who had received doses to the ovary of 5 Gy or more. No estimate of risk per unit dose was presented.

A Swedish cohort study included 2007 women treated for metropathia hemorrhagica between 1912 and 1977. Of these, 788 received radiotherapy for this condition. The population was followed up for cancer mortality and incidence from 1958 to 1982, with a mean follow-up period of 28 years (Ryberg and others 1990). A total of 107 cancers were observed among irradiated women. The SIR for cancer was 1.22 among irradiated women and 1.09 among nonirradiated. A significant increase in the SIR for cancers at heavily irradiated sites in the pelvic area was only observed 30 years or more after irradiation. A decreased risk for breast cancer was also observed in this cohort, except for women treated at the age of 50 or more. No estimate of risk per unit dose was presented.

Hormonal Infertility

A U.S. cohort of 816 women who received X-ray therapy to the ovaries and/or pituitary gland for refractory hormonal infertility and amenorrhea between 1925 and 1961 was followed up until the end of 1990 (Ron and others 1994). The average duration of follow-up was 35 years. Individual organ doses were estimated from radiotherapy records. Average doses were 0.01 Gy to the breast, 0.9 Gy to the ovary, and 1.0 Gy to the sigmoid colon. Seventy-eight deaths from cancer occurred in this cohort. No increase in mortality rates was found for leukemia or sites directly exposed to radiation, such as the ovary or brain, based on a very small number of deaths (two leukemia, three ovary, and one brain cancer death). The SMRs were significantly elevated, however, for cancer of the colon (15 deaths) and for NHL (6 deaths). No estimate of risk per unit dose was presented.

Ankylosing Spondylitis

A U.K. cohort consisting of 15,577 patients diagnosed with ankylosing spondylitis between 1935 and 1957 was followed for mortality up to the end of 1991 (Weiss and others 1994). The average duration of follow-up was 25 years. Of these subjects, 14,566 had received X-ray treatment for their disease. Radiation doses to various organs were calculated for a sample of patients, and average estimated doses from all treatment courses occurring within 5 years of the initial treatment courses were attributed to all patients. The mean total body dose was estimated to be 2.6 Gy. Irradiated patients had a significantly greater mortality rate from cancer than expected from the national rates for England and Wales, and significant increases were seen for leukemia, NHL, multiple myeloma, and cancers of the esophagus, colon, pancreas, lung, bones, connective and soft tissue, prostate, bladder, and kidney. A linear dose-response model for all cancers except leukemia gave an ERR of 0.18 Gy−1 (95% CI 0.10, 0.27) 5–24 years after treatment (based on 741 deaths), decreasing significantly to 0.11 Gy−1 25 years or more (based on 845 deaths) after treatment. For lung cancer, the ERR was 0.09 Gy−1 (95% CI 0.03, 0.15) 5–24 years after treatment, based on 282 deaths and an average dose to the bronchi of 8.88 Gy. For stomach cancer, the ERR was −0.004 Gy−1 (95% CI −0.05, 0.05) 5–24 years after treatment, based on 127 deaths and an average stomach dose of 3.21 Gy. There was no increased risk in breast cancer in



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