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Biomedical subjects

J D Boice

Publications and source records attributed to J D Boice.

At least 109 records · Page 6Linked to original sources

Cancer following radiotherapy for peptic ulcer.

BACKGROUND: Radiotherapy for peptic ulcer was used between 1937 and 1965 to control excessive gastric acid secretions (mean dose, 14.8 Gy). Patients with this benign condition live many years after treatment and are at risk for late effects. PURPOSE: Our purpose was to investigate the risk of death from cancer following radiotherapy for peptic ulcer. METHODS: A mortality study was conducted of 3609 patients with peptic ulcer; 1831 were treated with radiation and 1778 were treated by other means. Extensive methods were used to trace patients. Radiation doses to specific organs were reconstructed from the original radiotherapy records. RESULTS: Nearly 70% of patients were found to have died. The average period of observation was 21.5 years (maximum 51 years). Compared with the general population, patients treated with or without radiation were at significantly increased risk of dying of cancer and non-malignant diseases of the digestive system. Risk of death due to heart disease was slightly higher following radiotherapy. Cancers of the stomach, pancreas, lung, and prostate were increased in both irradiated and nonirradiated patients. Radiotherapy was linked to significantly high relative risks (RRs) for all cancers combined (RR = 1.53; 95% confidence interval [CI] = 1.3-1.8), for cancers of the stomach (RR = 2.77; 95% CI = 1.6-4.8), pancreas (RR = 1.87; 95% CI = 1.0-3.4), and lung (RR = 1.70; 95% CI = 1.2-2.4), and for leukemia (RR = 3.28; 95% CI = 1.0-10.6). Radiation combined with surgery, or given to treat gastric ulcer, appeared to increase the risk of stomach cancer 10-fold, which was greater than the sum of individual effects. Patients with gastric ulcers were at higher risk for stomach cancer than patients with duodenal ulcers. CONCLUSIONS: Patients with peptic ulcer are at increased risk of dying of cancer, related in part to lifestyle factors and treatment. Radiotherapy and surgery together appear to induce carcinogenic processes that greatly enhance the development of stomach cancer. The risk of radiation-induced stomach cancer was 0.25 extra deaths per 10,000 persons per year per Gy, somewhat lower than reported in other studies. High-dose radiation may have increased the risk of pancreatic cancer, a condition rarely found elevated in irradiated populations, but misclassified death notices may have contributed to the excess. Cancer mortality remained high for up to 50 years, indicating that radiation damage may persist to the end of life.

Aged↗

Radon exposure in residences and lung cancer among women: combined analysis of three studies.

Lung cancer risk in relation to indoor radon was examined in three case-control studies in Stockholm (Sweden), New Jersey (United States), and Shenyang (People's Republic of China). Year-long measurements of radon gas were made in current and past homes of 966 women who developed lung cancer and of 1,158 control women, included in the combined analysis. Nearly 14 percent of the participants were estimated to have a time-weighted, mean, radon concentration in their homes of more than 4 pCi/l (150 Bq/m3) during the period from five to 35 years prior to the date of lung cancer diagnosis (or comparable date for controls). There was a tendency for risk to increase with increasing levels of radon in NJ and Stockholm, but the trends for individual studies and overall were not statistically significant. The estimates of the excess relative risk for indoor exposure per pCi/l were 0.18 (95 percent [CI] = -0.04-0.70) in NJ, 0.06 (CI = -0.05-0.34) in Stockholm, and -0.02 (CI = -infinity-0.03) for Shenyang; these estimates did not differ significantly from each other. The overall excess RR per pCi/l was 0.00 (CI = -0.05-0.07); the confidence limits were sufficiently broad, however, that the overall estimate was still compatible with extrapolations of risks from miners. Cigarette smoking was the predominant cause of lung cancer with the RR significantly elevated in all studies. Within smoking categories, the trend in risk with increasing mean radon concentration was inconsistent. Analyses of data from several studies are complicated by the possibility that there may exist important differences in study bases which might affect results, and which may be controlled only partially through adjustment procedures. Future efforts to combine various residential studies will need to be attentive to the intrinsic limitations of studies to detect low levels of risk as well as the unique uncertainties associated with estimating, accurately, cumulative exposure to indoor radon.

Adult↗

Mortality following radiation treatment for infertility of hormonal origin or amenorrhoea.

BACKGROUND: Between 1920 and 1965, radiation treatment to the ovaries and/or pituitary gland was used for refractory hormonal infertility and amenorrhoea. The potential carcinogenic effects of hormonal infertility, as well as exposure to relatively low doses of ovarian and pituitary radiation can be studied among patients receiving these treatments. METHODS: A cohort of 816 patients treated between 1925 and 1961 was identified from the medical records of a New York City radiologist. The mortality experience for 84% of these women was determined and radiation doses for individual patients were estimated. Doses were, on average, 87, 64, 54, and 29 cGy to the ovary, brain, colon, and active bone marrow, respectively. RESULTS: Compared with mortality rates in the US population, the risk of death was less than expected (standardized mortality ratio [SMR] = 0.87; 95% confidence interval [CI]: 0.75-1.00). Deaths due to circulatory and digestive diseases were significantly below expectation. Cancer mortality was about 10% higher than that expected based on New York City mortality rates. Based on a small number of cases, no increase was found for cancers of the ovary or brain, or leukaemia, sites for which direct radiation exposure occurred, but significant excesses of colon cancer and non-Hodgkin's lymphoma were observed. A deficit in mortality from female genital cancers was surprising, since nulliparity has been a consistently reported risk factor for cancers of the endometrium and ovary. Breast cancer mortality was close to expectation. CONCLUSIONS: Overall, this study provided little evidence that either infertility or its treatment with radiation increased the risk of total or cancer mortality.

Adolescent↗

Chromosome aberrations in lymphocytes from women irradiated for benign and malignant gynecological disease.

Excess leukemias have occurred after partial-body radiotherapy for cervical cancer and benign gynecological disease (BGD). However, the level of risk is nearly the same in both groups, about twofold, despite a tenfold difference in average dose to active bone marrow (8 Gy vs 0.7 Gy, respectively). High-dose cell killing has been postulated as one explanation for this apparent inconsistency. To examine whether chromosome aberration rates observed in lymphocytes many years after exposure might serve as population markers of cancer risk, blood samples were taken from 60 women treated for BGD (34 with radiation) and cytogenetic data compared with previous results from 96 women irradiated for cervical cancer. Remarkably, the rate of stable aberrations, which reflects nonlethal damage in surviving stem cells, was only slightly higher among the cancer patients. Thus the lower-dose regimens to treat benign disorders resulted in much higher aberration yields per unit dose than those for cervical cancer. Assuming that the fraction of cytogenetically aberrant stem cells that survive radiotherapy contributes to the leukemogenic process, these data are then consistent with the epidemiological observations of comparable overall leukemia risks seen in these two irradiated populations. Accordingly, for patient populations given partial-body radiotherapy, stable aberrations at a long time after exposure appear to serve as biomarkers of effective risk rather than as biomarkers of radiation dose received.

Aged↗

Exposure to radon progeny, tobacco use and lung cancer in a case-control study in southern China.

A case-control study of lung cancer in underground tin miners in southern China was conducted to examine the interplay between exposure to radon progeny and tobacco use. A total of 460 incident cases and 1,043 controls were evaluated. Among the exposed, mean radon progeny exposures were 600 and 427 working level months (WLM) for cases and controls, respectively. The excess relative risk per WLM (ERR/WLM) was 0.28% overall, with a 95% confidence interval of 0.1-0.6%, similar to the estimate from a cohort study in a related population of underground miners. The established patterns of lung cancer associated with radon were seen; the ERR/WLM decreased with attained age and time since last exposure. Conditional on total exposure, risk was highest for exposures delivered at a low rate. The ERR/WLM did not differ significantly among current and former smokers or within categories of time since last exposure. The relative risk relationship between exposure to radon progeny and tobacco use was consistent with a multiplicative model, but the best-fitting model was intermediate between additive and multiplicative; an additive association was rejected. Adjustment for exposure to inorganic arsenic, a known lung carcinogen, reduced the estimate of the ERR/WLM from 0.86% to 0.28%. The ERR/WLM estimate was homogeneous across subgroups defined by workers not exposed to arsenic and quartiles of cumulative arsenic exposure. Although squamous cell carcinoma was the predominant cell type, small cell and adenocarcinoma histologies appeared more strongly associated with exposure to radon progeny. The finding of a stronger trend with exposure with small cell carcinomas and adenocarcinomas, compared to squamous cell carcinomas, occurred primarily at younger ages at diagnosis. Finally, the risk of lung cancer was higher if exposure to radon progeny and tobacco use occurred together than if the exposure to radon progeny entirely preceded tobacco use.

Adult↗

Mortality from second tumors among long-term survivors of retinoblastoma.

BACKGROUND: Children diagnosed with retinoblastoma, a rare cancer of the eye, tend to develop and die of second primary cancers in childhood and adolescence, but few investigations have followed patients into adulthood. Retinoblastoma is frequently caused by inherited mutations of the RB1 tumor suppressor gene. Most patients with germline (hereditary) mutations have bilateral disease. PURPOSE: We sought to quantify the mortality from second malignancies among long-term survivors of retinoblastoma and to identify factors that predispose to these deaths. METHODS: A retrospective cohort study examined mortality among 1603 patients enrolled at 1 year after diagnosis of retinoblastoma during the period 1914-1984. Data on demography, family history, and retinoblastoma treatment were collected by medical chart review and questionnaire interview. Number of deaths, by cause, was compared with the corresponding expected figure based on U.S. mortality data for the general population for 1925-1990. RESULTS: Follow-up was complete for 1458 patients (91%) for a median of 17 years after retinoblastoma diagnosis. A total of 305 deaths occurred, 167 of them from retinoblastoma. There were 96 deaths from second primary tumors (relative risk [RR] = 30), 21 from other known causes (RR = 1.0), and 21 from ill-defined or unknown causes. Statistically significant excess mortality was found for second primary cancers of bone, connective tissue, and malignant melanoma and benign and malignant neoplasms of brain and meninges. Among 919 children with bilateral retinoblastoma, 90 deaths from second primary tumors occurred (RR = 60). Deaths from second tumors were more frequent among females (RR = 39) than males (RR = 22) (P = .007). The cumulative probability of death from second primary neoplasms was 26% at 40 years after bilateral retinoblastoma diagnosis, and additional cancer deaths occurred thereafter. Radiotherapy for retinoblastoma further increased the risk of mortality from second neoplasms. An excess of mortality from a second cancer, not seen in prior studies, was found among the 684 children with unilateral disease (RR = 3.1; 95% confidence interval = 1.0-7.3). CONCLUSIONS: These findings implicate germinal mutations in the retinoblastoma gene in second cancer mortality. Radiotherapy treatment for retinoblastoma appears to further enhance the inborn susceptibility to development of a second cancer. IMPLICATIONS: Patients with retinoblastoma, particularly bilateral retinoblastoma, should have careful follow-up, and interventions should be developed to reduce mortality from a second cancer.

Adolescent↗

Mortality among workers at a nuclear power plant in the United States.

A second follow-up of 9,000 workers at the Calvert Cliffs Nuclear Power Plant (MD, USA) identified 346 deaths in the years 1969-88, 101 of which were attributed to malignant neoplasms. The original study had the primary purpose of assessing the feasibility of studies of workers based upon individual plant and Nuclear Regulatory Commission records. The average, cumulative, occupational dose through 1984 was low, only 21 mSv, but ranged up to 470 mSv, with 12 percent of the workers receiving more than 50 mSv. Mortality from most causes of death was low and there was a deficit of deaths from diseases of the circulatory system. Ionizing radiation exposures were not related to the probability of death from neoplasms generally or from any specific form of cancer. There were only two deaths from leukemia, whereas four were expected at population death rates. Larger numbers of workers, followed for longer periods of time, are needed to determine the mortality risk to workers in the nuclear power industry. The difficulties in obtaining dose information for transient workers were so great, and so time consuming, as to make questionable the practicability of studying the workers at a large number of power plants in this way.

Adult↗

Estimating past exposure to indoor radon from household glass.

CR-39 plastic was attached to household glass objects to learn whether residual radioactivity from radon decay products could be measured and correlated with cumulative radon exposures over defined time periods. Such an approach could be used to increase the completeness of exposure data collected in epidemiologic studies of residential radon. Inability to estimate radon concentrations for all residences adversely effects statistical power and thus the ability to detect an effect of radon exposure on lung cancer risk. A feasibility study was performed to determine if affixing CR-39 surface monitors to selected glass, ceramic, or enameled objects provided comparable estimates of past residential radon exposure to those obtained from year-long ambient alpha track-etch measurements. The CR-39 measurements of alpha activity in the surface of selected objects correlated with ambient radon measurements (R2 = 0.48) provided that reliable information was obtained on the history and age of the objects. This technique has now been incorporated into an epidemiologic study of radon and lung cancer to more fully estimate past exposure to indoor radon.

Air Pollution, Indoor↗

Radiation and non-Hodgkin's lymphoma.

Lymphomas are rarely, if ever, found to be in excess following exposure to ionizing radiation. Hodgkin's disease has never been linked to radiation, and the evidence for non-Hodgkin's lymphoma (NHL) is very weak. Low doses of radiation from diagnostic X-ray procedures or from occupational exposures do not appear to cause NHL. Mortality studies of atomic bomb survivors in Japan and other epidemiological studies with quantitative estimates of radiation dose also fail to find dose-response relationships. NHL may arise infrequently following high-dose, possibly near lethal, radiation treatments. Immunosuppression associated with the disease being treated, such as Hodgkin's disease, may contribute to the development of NHL. If radiation does not cause NHL, at least not by its accepted mechanism of action of breaking chromosomes, creating rearrangements, gene deletions, and mutations, perhaps other environmental mutagens and clastogens should not be considered likely causes of NHL.

Humans↗

Preexisting lung disease and lung cancer among nonsmoking women.

Preexisting lung disease was examined as a risk factor for lung cancer in a population-based, case-control study of nonsmoking women in Missouri conducted between June 1, 1986, and April 1, 1991. A history of lung disease was reported by approximately 41% of 618 cases and 35% of 1,402 controls (odds ratio (OR) = 1.2; 95% confidence interval (Cl) 1.0-1.5. The risk was more pronounced when next-of-kin interviews were excluded (OR = 1.5). Previous lung disease was significantly related both to adenocarcinoma (OR = 1.4), which accounted for 62% of the cancers, and to all other cell types of lung cancer combined (OR = 1.8). Despite having discontinued smoking for more than 15 years, long-term ex-smokers were at a 2.2-fold risk of lung cancer compared with lifetime nonsmokers. Among lifetime nonsmokers, significant risks were noted for asthma (OR = 2.7) and pneumonia (OR = 1.5). Emphysema (OR = 2.6) and tuberculosis (OR = 2.0) were also significantly related to lung cancer, but only among former smokers. Chronic bronchitis was linked to elevated risks of nonadenocarcinomas only (OR = 2.3). Pleurisy was not reported more frequently by cases than by controls. Approximately 16% of all lung cancers among nonsmoking women could be attributed to previous lung diseases, most notably asthma, pneumonia, emphysema, and tuberculosis.

Adult↗

Adjuvant radiotherapy and risk of contralateral breast cancer.

BACKGROUND: The risk of contralateral breast cancer is increased twofold to fivefold for breast cancer patients. A registry-based cohort study in Denmark suggested that radiation treatment of the first breast cancer might increase the risk for contralateral breast cancer among 10-year survivors. PURPOSE: Our goal was to assess the role of radiation in the development of contralateral breast cancer. METHODS: A nested case-control study was conducted in a cohort of 56,540 women in Denmark diagnosed with invasive breast cancer from 1943 through 1978. Case patients were 529 women who developed contralateral breast cancer 8 or more years after first diagnosis. Controls were women with breast cancer who did not develop contralateral breast cancer. One control was matched to each case patient on the basis of age, calendar year of initial breast cancer diagnosis, and survival time. Radiation dose to the contralateral breast was estimated for each patient on the basis of radiation measurements and abstracted treatment information. The anatomical position of each breast cancer was also abstracted from medical records. RESULTS: Radiotherapy had been administered to 82.4% of case patients and controls, and the mean radiation dose to the contralateral breast was estimated to be 2.51 Gy. Radiotherapy did not increase the overall risk of contralateral breast cancer (relative risk = 1.04; 95% confidence interval = 0.74-1.46), and there was no evidence that risk varied with radiation dose, time since exposure, or age at exposure. The second tumors in case patients were evenly distributed in the medial, lateral, and central portions of the breast, a finding that argues against a causal role of radiotherapy in tumorigenesis. CONCLUSIONS: The majority of women in our series were perimenopausal or postmenopausal (53% total versus 38% premenopausal and 9% of unknown status) and received radiotherapy at an age when the breast tissue appears least susceptible to the carcinogenic effects of radiation. Based on a dose of 2.51 Gy and estimates of radiation risk from other studies, a relative risk of only 1.18 would have been expected for a population of women exposed at an average age of 51 years. Thus, our data provide additional evidence that there is little if any risk of radiation-induced breast cancer associated with exposure of breast tissue to low-dose radiation (e.g., from mammographic x rays or adjuvant radiotherapy) in later life.

Adult↗

Leukaemia incidence after iodine-131 exposure.

Leukaemia is one of the most prominent late effects of exposure to ionising radiation. We have studied the incidence of leukaemia among 46,988 Swedish patients exposed to iodine-131 (131I) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared with that expected based on incidence data from the general population. The mean absorbed dose to the bone marrow was estimated as 14 mGy (range 0.01-2.226). 195 leukaemias occurred more than 2 years after exposure, and the standardised incidence ratio (SIR) was 1.09 (95% confidence interval 0.94-1.25). Similar, but again not significantly, increased risks were seen for chronic lymphocytic leukaemia (CLL) (SIR = 1.08), a malignant condition not found to be increased after irradiation, and for non-CLL (SIR = 1.09). The risk of leukaemia did not vary by sex, age, time, or radiation dose from 131I. One reason for the absence of a radiation effect, other than chance, includes the possible lowering of risk when exposure is protracted over time as occurs with 131I. Excess leukaemia risks of more than 25% could thus be excluded with high assurance in this population of mainly adults. These results should be reassuring to patients exposed to 131I in medical practice and to most individuals exposed to the fall-out from the Chernobyl accident.

Adolescent↗

Risk of leukemia after chemotherapy and radiation treatment for breast cancer.

BACKGROUND: Few studies have evaluated the late effects of adjuvant chemotherapy for breast cancer. Moreover, the relation between the risk of leukemia and the amount of drug given and the interaction of chemotherapy with radiotherapy have not been described in detail. METHODS: We conducted a case-control study in a cohort of 82,700 women given a diagnosis of breast cancer from 1973 to 1985 in five areas of the United States. Detailed information about therapy was obtained for 90 patients with leukemia and 264 matched controls. The dose of radiation to the active marrow was estimated from individual radiotherapy records (mean dose, 7.5 Gy). RESULTS: The risk of acute nonlymphocytic leukemia was significantly increased after regional radiotherapy alone (relative risk, 2.4), alkylating agents alone (relative risk, 10.0), and combined radiation and drug therapy (relative risk, 17.4). Dose-dependent risks were observed after radiotherapy and treatment with melphalan and cyclophosphamide. Melphalan was 10 times more leukemogenic than cyclophosphamide (relative risk, 31.4 vs. 3.1). There was little increase in the risk associated with total cyclophosphamide doses of less than 20,000 mg. CONCLUSIONS: Although leukemia occurs in few patients with breast cancer, significantly elevated risks were linked to treatments with regional radiation and alkylating agents. Melphalan is a more potent leukemogen than cyclophosphamide or radiotherapy. Low risks were associated with the levels of cyclophosphamide in common use today. Systemic drug therapy combined with radiotherapy that delivers high doses to the marrow appears to enhance the risk of leukemia.

Aged↗