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Biomedical subjects

J D Boice

Publications and source records attributed to J D Boice.

At least 145 records · Page 8Linked to original sources

Cancer risks in thyroid cancer patients.

Cancer risks were studied in 834 thyroid cancer patients given 131I (4,551 MBq, average) and in 1,121 patients treated by other means in Sweden between 1950 and 1975. Record-linkage with the Swedish Cancer Register identified 99 new cancers more than 2 years after 131I therapy [standardised incidence ratio (SIR) = 1.43; 95% confidence interval (CI) 1.17-1.75] vs 122 (SIR = 1.19; 95% CI 0.88-1.42) in patients not receiving 131I. In females treated with 131I overall SIR was 1.45 (95% CI 1.14-1.83) and significantly elevated were noted for tumours of the salivary glands, genital organs, kidney and adrenal gland. No elevated risk of a subsequent breast cancer or leukaemia was noted. SIR did not change over time, arguing against a strong radiation effect of 131I. Organs that were estimated to have received more than 1.0 Gy had together a significantly increased risk of a subsequent cancer following 131I treatment (SIR = 2.59; n = 18). A significant trend was seen for increasing activities of 131I with highest risk for patients exposed to greater than or equal to 3,664 MBq (SIR = 1.80; 95% CI 1.20-2.58). No specific cancer or group of cancers could be convincingly linked to high-dose 131I exposures since SIR did not increase after 10 years of observation. However, upper confidence intervals could not exclude levels of risk that would be predicted based on data from the study of atomic bomb survivors. We conclude that the current practice of extrapolating the effects of high-dose exposures to lower-dose situations is unlikely to seriously underestimate radiation hazards for low LET radiation.

Female↗

Cancer incidence following hospitalization for multiple sclerosis in Denmark.

Incidence of various cancers was evaluated in a cohort of 5359 multiple sclerosis (MS) patients, identified through hospital discharge records between 1977 and 1987 and followed for an average of 5.2 years. Computerized linkage with the Danish Cancer Registry uncovered 210 cancer cases which was significantly more than expected based on national rates (relative risk (RR) = 1.29). Over half of the excess, however, was observed for non-melanoma skin cancer and tumors of the urinary tract, which may be related to increased medical surveillance among MS patients compared to the Danish population as a whole. There was a significant excess of nasopharyngeal carcinomas in the cohort (RR = 17.3), but based on only 3 cases and seen only among women. Hematologic and lymphatic malignancies were not increased, adding little support to previous suggestions of a possible association of these malignancies with MS. An excess of brain tumors, seen only in women, may represent situations where the tumor caused symptoms which were interpreted as MS. Overall, the data suggest that a patient with MS is not at unusual risk for subsequent cancer development, but the relatively short follow-up of the population is a limitation of the investigation.

Adolescent↗

Frequent chest X-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts.

The incidence of breast cancer was determined in 4940 women treated for tuberculosis between 1925 and 1954 in Massachusetts. Among 2573 women examined by X-ray fluoroscopy an average of 88 times during lung collapse therapy and followed for an average of 30 years, 147 breast cancers occurred in contrast to 113.6 expected [observed/expected (O/E) = 1.29; 95% confidence interval (CI) = 1.1-1.5]. No excess of breast cancer was seen among 2367 women treated by other means: 87 observed versus 100.9 expected. Increased rates for breast cancer were not apparent until about 10 to 15 years after the initial fluoroscopy examination. Excess risk then remained high throughout all intervals of follow-up, up to 50 years after first exposure. Age at exposure strongly influenced the risk of radiation-induced breast cancer with young women being at highest risk and those over age 40 being at lowest risk [relative risk (RR) = 1.06]. Mean radiation dose to the breast was estimated to be 79 cGy, and there was strong evidence for a linear relationship between dose and breast cancer risk. Allowing for a 10-year minimum latent period, the relative risk at 1 Gy was estimated as 1.61 and the absolute excess as 10.7 per 10(4) woman-years per gray. When compared to other studies, our data suggest that the breast is one of the most sensitive tissues to the carcinogenic force of radiation, that fractionated exposures are similar to single exposures of the same total dose in their ability to induce breast cancer, that risk remains high for many years after exposure, and that young women are especially vulnerable to radiation injury.

Breast Neoplasms↗

Radiation-induced skin carcinomas of the head and neck.

Radiation exposures to the scalp during childhood for tinea capitis were associated with a fourfold increase in skin cancer, primarily basal cell carcinomas, and a threefold increase in benign skin tumors. Malignant melanoma, however, was not significantly elevated. Overall, 80 neoplasms were identified from an extensive search of the pathology logs of all major hospitals in Israel and computer linkage with the national cancer registry. Radiation dose to the scalp was computed for over 10,000 persons irradiated for ringworm (mean 7 Gy), and incidence rates were contrasted with those observed in 16,000 matched comparison subjects. The relative risk of radiogenic skin cancer did not differ significantly between men or women or by time since exposure; however, risk was greatest following exposures in early childhood. After adjusting for sex, ethnic origin, and attained age, the estimated excess relative risk was 0.7 per Gy and the average excess risk over the current follow-up was 0.31/10(4) PY-Gy. The risk per Gy of radiation-induced skin cancer was intermediate between the high risk found among whites and no risk found among blacks in a similar study conducted in New York City (Shore et al., Radiat. Res. 100, 192-204, 1984). This finding suggests the role that subsequent exposure to uv radiation likely plays in the expression of a potential radiation-induced skin malignancy.

Adolescent↗

Prenatal X-ray exposure and childhood cancer in Swedish twins.

The association between X-ray exposure in utero and childhood cancer was studied in a case-control study, nested in a national cohort of Swedish twin births. Records of the Swedish Twin Register for those born 1936-1967 (n = 83,316) were linked to the Swedish Cancer Register (1958-1983) and the Swedish Cause-of-Death Register (1952-1983). Ninety-five cases of childhood cancer before the age of 16 were identified. Two controls from the Twin Register were matched to each case by sex and year of birth. Maternal X-rays during pregnancy were documented for 41% of the cases and 36% of the controls. The crude relative risk of any childhood cancer associated with any prenatal X-ray was 1.2 (95% CI; 0.7-2.1). For the cases 64% of the X-rayed women had had abdominal X-rays, the numbers for the controls were 57%. Fifty-nine per cent of the X-rayed women had had abdominal X-rays, which were associated with a relative risk for all cancers of 1.4 (Cl; 0.8-2.5), leukemias 1.7 (Cl; 0.7-4.1) and tumors of the central nervous system 1.5 (Cl; 0.5-4.2). There was no apparent confounding by mother's age, drug use, obstetric complications, previous miscarriages, social class or length of pregnancy. The observed relative risks of cancer following prenatal X-ray exposure are consistent with previous studies, suggesting that the developing fetus may be more sensitive to the carcinogenic effects of ionizing radiation than are children irradiated post-natally.

Adolescent↗

Indoor radon and lung cancer in China.

Radon has long been known to contribute to risk of lung cancer, especially in undergound miners who are exposed to large amounts of the carcinogen. Recently, however, lower amounts of radon present in living areas have been suggested as an important cause of lung cancer. In an effort to clarify the relationship of low amounts of radon with lung cancer risk, we placed alpha-track radon detectors in the homes of 308 women with newly diagnosed lung cancer and 356 randomly selected female control subjects of similar age. Measurements were taken after 1 year. All study participants were part of the general population of Shenyang, People's Republic of China, an industrial city in the northeast part of the country that has one of the world's highest rates of lung cancer in women. The median time of residence in the homes was 24 years. The median household radon level was 2.3 pCi/L of air; 20% of the levels were greater than 4 pCi/L. Radon levels tended to be higher in single-story houses or on the first floor of multiple-story dwellings, and they were also higher in houses with increased levels of indoor air pollution from coal-burning stoves. However, the levels were not higher in homes of women who developed lung cancer than in homes of controls, nor did lung cancer risk increase with increasing radon level. No association between radon and lung cancer was observed regardless of cigarette-smoking status, except for a nonsignificant trend among heavy smokers. No positive associations of lung cancer cell type with radon were observed, except for a nonsignificant excess risk of small cell cancers among the more heavily exposed residents. Our data suggest that projections from surveys of miners exposed to high radon levels may have overestimated the overall risks of lung cancer associated with levels typically seen in homes in this Chinese city. However, further studies in other population groups are needed to clarify the carcinogenic potential of indoor radon.

Adult↗

Cancer incidence among medical diagnostic X-ray workers in China, 1950 to 1985.

A second follow-up of 27,011 diagnostic X-ray workers in China revealed a 21% greater incidence of cancer than expected based on the experience of 25,782 physicians who did not routinely use X-rays (RR = 1.21; 95% Cl: 1.08 to 1.35). This risk is lower than the 50% excess reported previously and reflects, in part, the reduced risk among workers first employed after 1965, when hospital exposures to radiation probably were lower than in earlier years. The X-ray workers were employed between 1950 and 1985 and followed for an average of 16.1 years. Significantly elevated risks were seen for leukemia (RR = 2.4, n = 34 cases), and cancers of the esophagus (RR = 5.2, n = 19), liver (RR = 1.8, n = 65), and skin (RR = 2.8, n = 9). Cancers of the breast (RR = 1.5, n = 20), thyroid (RR = 1.7, n = 8), and bone (RR = 7.6, n = 4) also occurred more often than expected. Non-significant deficits were observed for cancers of the oral cavity and pharynx (RR = 0.6, n = 16), colon and rectum (RR = 0.8, n = 20), stomach (RR = 0.8, n = 36), and lung (RR = 0.9, n = 45). Excess risks for leukemia and esophageal cancer were seen among men but not among women. The RR for leukemia was higher for X-ray workers who began employment before 1970 than for those who started more recently and also for those who were young when employment began. The patterns of risk associated with duration of work, and with age and calendar time of initial employment, suggest that the excesses of leukemia and skin cancer, and, possibly, cancers of the breast and thyroid, were due to occupational exposure to X-rays. However, there was little evidence that radiation contributed to the increased occurrences of liver or esophageal cancers.

Adult↗

Leukemia following chemotherapy for breast cancer.

Leukemia following chemotherapy for breast cancer was studied among patients diagnosed during 1973-1985 within the population-based tumor registries in the Surveillance, Epidemiology, and End Results Program. Among 13,734 women given initial chemotherapy, 24 developed acute nonlymphocytic leukemia (ANLL) compared to 2.1 expected based on general population rates (observed/expected = 11.5; 95% confidence interval = 7.4-17.1). Overall, 58 excess ANLL occurred per 100,000 women-years at risk for patients treated with chemotherapy. The cumulative incidence was 0.7% at 10 years. Risk remained high over all periods of observation up to 9 years after treatment. Among 7974 women treated only with surgery during 1973 and 1974, a period before the widespread use of adjuvant chemotherapy for breast cancer, ANLL was not significantly increased (observed = 7, expected = 5.1). A case-control study was then conducted in Connecticut to evaluate in more detail the risk associated with adjuvant chemotherapy in the general population. Among 20 cases (17 incident leukemias and 3 deaths due to preleukemia) and 60 matched controls, alkylating agents were linked to an 11.9-fold risk of ANLL and preleukemia (95% confidence interval = 2.6-55). Chemotherapy regimens including melphalan were related to a higher risk of leukemic conditions than those including cyclophosphamide. These data suggest that women in the general population treated with adjuvant chemotherapy for breast cancer are at an increased risk of leukemia, that the risk remains high among long-term survivors, and that risk differs by type of alkylating agent administered.

Age Factors↗

Thyroid nodularity and chromosome aberrations among women in areas of high background radiation in China.

Thyroid nodularity following continuous low-dose radiation exposure in China was determined in 1,001 women aged 50-65 years who resided in areas of high background radiation (330 mR/yr) their entire lives, and in 1,005 comparison subjects exposed to normal levels of radiation (114 mR/yr). Cumulative doses to the thyroid were estimated to be of the order of 14 cGy and 5 cGy, respectively. Personal interviews and physical examinations were conducted, and measurements were made of serum thyroid hormone levels, urinary iodine concentrations, and chromosome aberrations in circulating lymphocytes. For all nodular disease, the prevalences in the high background and control areas were 9.5% and 9.3%, respectively. For single nodules, the prevalences were 7.4% in the high background area and 6.6% in the control area (prevalence ratio = 1.13; 95% confidence interval = 0.82-1.55). There were no differences found in serum levels of thyroid hormones. Women in the high background region, however, had significantly lower concentrations of urinary iodine and significantly higher frequencies of stable and unstable chromosome aberrations. Increased intake of allium vegetables such as garlic and onions was associated with a decreased risk of nodular disease, which seems consistent with experimental studies suggesting that allium compounds can inhibit tumor growth and proliferation. The prevalence of mild diffuse goiter was higher in the high background radiation region, perhaps related to a low dietary intake of iodine. These data suggest that continuous exposure to low-level radiation throughout life is unlikely to appreciably increase the risk of thyroid cancer. However, such exposure may cause chromosomal damage.

Autoantibodies↗

Thyroid nodularity after childhood irradiation for lymphoid hyperplasia: a comparison of questionnaire and clinical findings.

Ionizing radiation is a well-established cause of thyroid cancer and nodularity, however, important questions relating to the magnitude of the risk following low-dose medical exposures remain unresolved. To address these issues, we conducted a follow-up study of 1590 individuals treated between 1938 and 1969 with X-rays for childhood lymphoid hyperplasia (av. thyroid dose = 24 cGy) and 1499 individuals treated with surgery only. Thyroid nodularity was determined from self-administered questionnaires completed by 1195 irradiated and 1063 surgically-treated subjects and from clinical examinations of 602 irradiated and 457 non-irradiated subjects. A much higher relative risk (RR) for radiation-induced thyroid nodules was estimated from the questionnaire than from the clinical examination data, 15.8 and 2.7, respectively. (The corresponding estimates of excess RR per cGy were 64 and 7%). Analysis of the examination data revealed a strong dose-response relationship, similar excess RR/cGy for males and females, and an inverse relationship with age at exposure. Although the thyroid gland is one of the most sensitive organs to the neoplastic effects of radiation, the radiation-induced risk of thyroid nodularity reported from questionnaire studies may over-estimate the true risk.

Adult↗

Cancer in children of epileptic mothers and the possible relation to maternal anticonvulsant therapy.

Cancer incidence among 3,727 offspring of women hospitalised for epilepsy in Denmark between 1933 and 1962 was evaluated in a record-linkage survey with the national cancer registry. The children were identified from hospital charts, population listings, and parish registries. For all children (born before and after their mothers' hospitalisation), no excess of cancer was found in comparison with the general population (49 observed vs 53.8 expected). Among the 2,579 children born after their mothers' first admission for epilepsy, and thus presumably exposed in utero to anticonvulsant drugs, 14 cancers were identified compared to 13.8 expected (relative risk 1.0; 95% confidence interval 0.6-1.7). Contrary to some previous reports, cancers of the brain and nervous system were not significantly increased (3 observed vs 2.2 expected). These data provide no evidence that anticonvulsant drugs are transplacental carcinogens, and indicate that overall increases in risk as high as 80% are unlikely.

Adolescent↗

Cancer mortality following radium treatment for uterine bleeding.

Cancer mortality in relation to radiation dose was evaluated among 4153 women treated with intrauterine radium (226Ra) capsules for benign gynecologic bleeding disorders between 1925 and 1965. Average follow up was 26.5 years (maximum = 59.9 years). Overall, 2763 deaths were observed versus 2687 expected based on U.S. mortality rates [standardized mortality ratio (SMR) = 1.03]. Deaths due to cancer, however, were increased (SMR = 1.30), especially cancers of organs close to the radiation source. For organs receiving greater than 5 Gy, excess mortality of 100 to 110% was noted for cancers of the uterus and bladder 10 or more years following irradiation, while a deficit was seen for cancer of the cervix, one of the few malignancies not previously shown to be caused by ionizing radiation. Part of the excess of uterine cancer, however, may have been due to the underlying gynecologic disorders being treated. Among cancers of organs receiving average or local doses of 1 to 4 Gy, excesses of 30 to 100% were found for leukemia and cancers of the colon and genital organs other than uterus; no excess was seen for rectal or bone cancer. Among organs typically receiving 0.1 to 0.3 Gy, a deficit was recorded for cancers of the liver, gall bladder, and bile ducts combined, death due to stomach cancer occurred at close to the expected rate, a 30% excess was noted for kidney cancer (based on eight deaths), and there was a 60% excess of pancreatic cancer among 10-year survivors, but little evidence of dose-response. Estimates of the excess relative risk per Gray were 0.006 for uterus, 0.4 for other genital organs, 0.5 for colon, 0.2 for bladder, and 1.9 for leukemia. Contrary to findings for other populations treated by pelvic irradiation, a deficit of breast cancer was not observed (SMR = 1.0). Dose to the ovaries (median, 2.3 Gy) may have been insufficient to protect against breast cancer. For organs receiving greater than 1 Gy, cancer mortality remained elevated for more than 30 years, supporting the notion that radiation damage persists for many years after exposure.

Adolescent↗

Leukemia among medical diagnostic X-ray workers in China.

The incidence of leukemia among 27,011 medical diagnostic X-ray workers was compared with that among 25,782 other medical specialists employed between 1950 and 1985 in China. A significantly elevated risk of leukemia was seen among diagnostic X-ray workers. The relative risk (RR) of leukemia was 2.4 (95% CI = 1.3-4.1) based on the rate observed in the comparison group, and 2.3 when the rate in a Shanghai population was used. The elevated incidence of leukemia was restricted to male X-ray workers, and the relative risk of leukemia was higher for X-ray workers who began employment before 1970 than for those who started work more recently. The RR for leukemia was highest among workers who had been employed for 10-15 years, but the incidence was not apparently elevated further among those who had been employed for more than 20 years. The risk was more pronounced in workers who had begun their jobs before the age of 20 years, and it appeared to decrease with increasing age at first employment. The variation in risk with the duration of employment, age and the calendar time when diagnostic radiological work began indicates that the elevated incidence of leukemia is attributable to occupational exposure to X-rays.

Adult↗

Leukemia following radiotherapy for uterine bleeding.

Mortality due to leukemia among 4483 women treated with radiation to control uterine bleeding between 1925 and 1965 was twice as high as expected based on U.S. population rates (standardized mortality ratio (SMR) = 2.0; 95% confidence interval (CI): 1.4 to 2.8). Women were followed for an average of 26.4 years. Relative risk was highest 2 to 5 years after treatment (SMR = 8.1) and among women over 55 years at irradiation (SMR = 5.8). The usual method of treatment was intrauterine radium. Average radiation dose to active bone marrow was estimated on the basis of original radiotherapy records (median, 53 cGy). A linear dose-response model provided an adequate fit to the data. The average excess relative risk was 1.9% per cGy (95% CI: 0.8 to 3.2), and the average absolute risk was 2.6 excess leukemia deaths per million women per year per cGy (95% CI: 0.9 to 4.8). Chronic myeloid leukemia predominated during the first 15 years following exposure, whereas acute leukemias and chronic lymphatic leukemia were most common thereafter. The radiation doses experienced during treatment of benign gynecologic disease appear to result in greater leukemia risk per cGy average marrow dose than the considerably higher doses used to treat malignant disease, perhaps because of a decreased likelihood of killing potentially leukemic cells.

Adolescent↗

Chromosome aberrations in relation to radiation dose following partial-body exposures in three populations.

Structural chromosome aberrations were evaluated in peripheral blood samples obtained from three populations exposed to partial-body irradiation. These included 143 persons who received radiotherapy for enlarged thymus glands during infancy and 50 sibling controls; 79 persons irradiated for enlarged tonsils and 81 persons surgically treated for the same condition during childhood; and 77 women frequently exposed as young adults to fluoroscopic chest X rays during lung collapse treatment for tuberculosis (TB) and 66 women of similar ages treated for TB with other therapies. Radiation exposures occurred 30 and more years before blood was drawn. Doses to active bone marrow averaged over the entire body were 21, 6, and 14 cGy for the exposed thymic, tonsil, and TB subjects, respectively. Two hundred metaphases were scored for each subject, and the frequencies of symmetrical (stable) and asymmetrical (unstable) chromosome aberrations were quantified in 97,200 metaphases. Cells with stable aberrations were detected with greater frequency in the irradiated subjects compared with nonirradiated subjects in all three populations, and an overall test for an association between stable aberrations and partial-body ionizing radiation was highly significant (P less than 0.001). We found no evidence that radiation-induced aberrations varied by age at exposure. These data show that exposure of children or young adults to partial-body fractionated radiation can result in detectable increased frequencies of stable chromosome aberrations in circulating lymphocytes 30 years later, and that these aberrations appear to be informative as biological markers of population exposure.

Chromosome Aberrations↗