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The association between arsenic ingestion and cancer has been documented for more than a century. Previous studies showed that the carcinogenic effects of arsenic on the urinary system are cell-type specific. To evaluate whether this is also true for skin cancers, we conducted an ecological study in 243 townships in Taiwan.The arsenic exposure was assessed on the basis of measurement reports from a previous survey, and cases of skin cancer were identified using the information gathered by the National Cancer Registry Program. We analyzed the data by regression models using multiple variables to describe the exposure status, and an urbanization index was also included in the models to adjust for the effects of urbanization.A total of 2369 patients with skin cancer, comprising 1415 men and 954 women, were registered between 1 January 1980 and 31 December 1989. Among the three major cell types of skin cancer, squamous cell carcinoma and basal cell carcinoma appear to be associated with ingestion of arsenic. Such an association was not observed for malignant melanoma.The results suggested that the carcinogenicity of arsenic on skin is cell-type specific, which is compatible with the findings in previous studies on urinary cancers.

Prediction of cancer risk is a minor component of current health risk appraisals. Perception of individual cancer risk is poor. A Cancer Risk Index was developed to predict individual cancer risk for cancers accounting for 80% of the cancer burden in the United States.We used group consensus among researchers at the Harvard Medical School and Harvard School of Public Health to identify risk factors as definite, probable and possible causes of cancer. Risk points were allocated according to the strength of the causal association and summed. Population average risk of cancer and cumulative 10-year risk was obtained from SEER data. Individual ranking relative to the population average was determined. The risk index was evaluated for validity using colon cancer incidence in prospective cohort data.The Harvard Cancer Risk Index provides a broad classification of cancer risk. Validation against cohort data shows good agreement for colon cancer.The Harvard Cancer Risk Index offers a simple estimation of personal risk of cancer. It may help inform users of the major risk factors for cancer and identify changes in lifestyle that will reduce their risk. It offers the potential for tailored health-promotion messages.

Results are reported from a nested case-control study of 60 esophageal cancer deaths among 46,384 automobile manufacturing workers potentially exposed to metalworking fluids (MWF) in machining and grinding operations.By using incidence-density sampling, controls were selected with a sampling ratio of 20:1 from among co-workers who remained at risk by the age of death of the case, matched on race, gender, plant, and year of birth. Conditional logistic regression was used to evaluate the risk associated with cumulative exposure (mg/m3-years) to each of three types of metalworking fluid (straight, soluble, and synthetic MWF), as well as with years of exposure to selected components of MWF, including nitrosamines, sulfur, biocides, and several metals.Esophageal cancer was found to be significantly associated with exposure to both soluble and synthetic MWF in grinding operations. The odds ratios (ORs) for grinding with soluble MWF were elevated at 2.5 or greater in all categories of cumulative exposure, although the exposure-response trend was statistically significant only when exposure was measured as duration. Those with 12 or more years exposure to soluble MWF in grinding operations experienced a 9.3-fold relative risk of esophageal cancer mortality (95% CI = 2.1-42.1). The OR for ever grinding with synthetic MWF was 4.1 (95% CI = 1.1-15.0). Elevated risk was also associated with two agents found in both synthetic and soluble fluids, nitrosamines, and biocides. For exposure to nitrosamines, the OR was 5.4 (95% CI = 1.5-19.9); for biocides the OR was 3.8 (95% CI = 0.8-18.9). However, because the same workers were exposed to grinding with synthetics, nitrosamines and biocides, it was not possible to separate the specific risks associated with these components.

A total of 1,811 automobile workers at three General Motors facilities were evaluated by questionnaire for possible respiratory effects resulting from airborne exposures to metal-working fluids (MWF): 1,042 currently worked as machinists and were exposed to one of three types of MWF aerosols (straight mineral oils, soluble oil emulsions, or water-based synthetic fluids that contained no oils); 769 assembly workers, without direct exposure, served as an internal reference group (of these, 239 had never worked as machinists). Symptoms of usual cough, usual phlegm, wheezing, chest tightness, and breathlessness, as well as physician-diagnosed asthma, and chronic bronchitis were the primary outcomes examined. Machinists as a whole had higher prevalence of cough, phlegm, wheezing, and breathlessness than that of assembly workers. Adjusting for confounding, phlegm and wheeze were associated with increasing levels of current exposure to straight oils; cough, phlegm, wheeze, chest tightness, and chronic bronchitis were associated with increasing levels of current exposure to synthetics. In models that included both past and current exposure, only current exposures to straight and synthetic fluids were associated with current symptoms.

Results are presented from a case-control study of 97 cases of pancreatic cancer nested in a cohort of workers from three automobile manufacturing plants. Risk was examined for lifetime exposure to straight, soluble, and synthetic metalworking fluids, as used in specific machining or grinding operations, as well as for constituents of the fluids. Pancreatic cancer was associated with exposure to synthetic fluids in grinding operations, with an odds ratio of 3.0 (95% CI: 1.2-7.5) among those with more than 1.4 mg/m3-years of exposure. We were unable to examine synthetic exposure in the absence of grinding because there was virtually no exposure to synthetics in machining operations in this study population. Although a disproportionately high percent of the cases were black, no black workers had any exposure to synthetic fluids, and no other measured exposure was found to be related to risk. Thus, the previously documented excess risk of pancreatic cancer among blacks in this cohort remains unexplained.

This report describes the reanalysis of a cross-sectional study of asthma in a large cohort of autoworkers with exposure to metalworking fluids (MWF). There is strong evidence from case reports, clinical studies, and medical surveillance data that exposure to MWF can cause asthma, yet no association was found in the original analysis. The central hypothesis of the reanalysis was that the absence of an association between asthma and MWF exposure was the result of bias caused by the self-selection of asthmatics out of exposed jobs. We addressed the potential job transfer bias by redefining exposure and disease status at the time of asthma onset, rather than at the time of the health survey. This permitted us to treat the cross-sectional study as if it were a historical cohort study, despite the fact that the population was a biased sample of the full cohort. This approach resulted in a significantly elevated incidence rate ratio of 3.2 (95% CI: 1.2-8.3) for synthetic MWF estimated in a Cox proportional hazards model. Although the cross-sectional design makes it impossible to document or control for differential selection out of the workforce, the approach described here provides a strategy for reducing the healthy-worker effect due to job transfer bias in cross-sectional studies.

Machining fluids are diverse products that contain numerous additives and contaminants, including polycyclic aromatic hydrocarbons. Studies treating machining fluids as an aggregate exposure have found both positive and negative associations with lung cancer. In this nested case-control study of automotive workers (667 cases and 3,041 matched controls), individual estimates of exposure quantity and duration for specific classes of machining fluids were derived. An inverse dose-response relationship was found between synthetic machining fluids and lung cancer mortality, with an odds ratio of 0.6 (95% CI = 0.4, 0.8) for the highest level of lifetime exposure. The relationship was strongest for recent exposures. There was little evidence of an association with soluble or straight oil machining fluids. Risks were inconsistently elevated in workers exposed to aluminum. Results from this study provide strong evidence that exposure to machining fluids is not associated with an increased risk of lung cancer mortality in automotive workers.

The relationship between exposure to sparsely ionizing radiation and mortality due to cancers of hematopoietic and lymphopoietic tissues was studied among 12,955 women treated for benign gynecological disorders at any of 17 hospitals in New England or New York State and followed for an average of 25 years; 9770 women were treated by radiation (intracavitary 226Ra, external-beam X rays), while 3185 were treated by other methods, including curettage, surgery, and hormones. The average age at treatment was 46.5 years, and the mean dose to active bone marrow among irradiated women was 119 cGy. Forty deaths due to acute, myelocytic, or monocytic leukemia were observed among irradiated women. This number was 70% higher than expected based on U.S. mortality rates [standardized mortality ratio (SMR) = 1.7; 90% confidence interval (CI) 1.3-2.3]. A deficit was recorded among nonirradiated women, based on three observed deaths (SMR = 0.5; 90% CI 0.1-1.2). A well-defined gradient in the SMR with dose among exposed women was not detected. The SMR was highest within 5 years after irradiation but remained elevated even after 30 years. The temporal pattern differed by subtype of leukemia: excess mortality due to chronic myelocytic leukemia occurred almost exclusively within the first 15 years, whereas the SMR for acute leukemia, though also elevated, varied little over time. Cancers of lymphoreticular tissue occurred more often than expected based on U.S. mortality rates, but not appreciably differently for irradiated and nonirradiated women. There was little or no evidence of effects attributable to radiotherapy for chronic lymphocytic leukemia [relative risk (RR) = 1.1; 90% CI 0.5-3.0], Hodgkin's disease (RR = 0.9; 90% CI 0.3-3.2), non-Hodgkin's lymphoma (RR = 0.9; 90% CI 0.6-1.6), or multiple myeloma (RR = 0.6; 90% CI 0.3-1.4). These results corroborate previous findings indicating that acute and myelocytic leukemias are the most prominent malignancies after exposure to sparsely ionizing radiation, occurring in excess shortly after irradiation, and that lymphomas are either not caused by radiation or are induced only rarely.

We assessed the association between first-trimester vaginal bleeding and singleton infant outcomes in a hospital-based population of 11,444 nondiabetic women. Low birth weight (LBW), shortened gestation, LBW at term, and neonatal death occurred more often in women reporting first-trimester bleeding than in those who never bled. These relationships remained statistically significant after adjusting for confounding factors. Women who experienced vaginal bleeding limited to the first trimester (N = 1174) had double the risk of delivering a preterm infant compared with those experiencing no bleeding (adjusted risk ratio = 2.0; 95% confidence interval 1.6-2.5). Bleeding limited to the first trimester was associated with a 1.6-fold risk of delivery of a term LBW infant (95% confidence interval 1.3-2.0). These results suggest that first-trimester vaginal bleeding is an important correlate of adverse infant outcomes.

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.

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.

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.

A retrospective follow-up study of 7338 women with either nontoxic nodular goiter, thyroid adenoma, hyperthyroidism, hypothyroidism, Hashimoto's thyroiditis, or no thyroid disease was conducted. All women patients at the Massachusetts General Hospital Thyroid Clinic who were seen between 1925 and 1974 and who were treated for a minimum of 1 year were traced. A total of 2231 women (30.4%) were dead and 2012 women (27.4%) were alive as of December 31, 1978. Partial follow-up information was available for the remaining 3095 women (42.2%). The average length of follow-up was 15.2 years. When losses to follow-up were withdrawn at the time of their loss, the standardized mortality ratios (SMR) for all causes of death were 1.2 [95% confidence interval (CI), 1.1-1.3] for women with nontoxic nodular goiter, 1.2 (95% CI 1.0-1.3) for those with thyroid adenoma, 1.4 (95% CI 1.3-1.5) for women with hyperthyroidism, 1.5 (95% CI 1.3-1.7) for hypothyroid women, 1.2 (95% CI 0.9-1.5) for those with Hashimoto's thyroiditis, and 1.5 (95% CI 1.4-1.6) for those without thyroid disease. For deaths from all cancers, the standardized mortality ratios were 1.5 (95% CI 1.2-1.8) for women with nontoxic nodular goiter, 1.5 (95% CI 1.1-1.9) for those with thyroid adenoma, 1.2 (95% CI 1.0-1.4) for women with hyperthyroidism, 1.0 (95% CI 0.7-1.4) for the hypothyroid women, 1.2 (95% CI 0.7-2.1) for those with Hashimoto's thyroiditis, and 1.3 (95% CI 1.0-1.5) for those women without thyroid disease. When specific cancer sites were studied, excess numbers of deaths were observed from breast cancer in women with nontoxic nodular goiter (SMR = 1.6, 95% CI 1.0-2.6) and from lymphatic and hematopoietic cancer in women with nontoxic nodular goiter (SMR = 2.4, 95% CI 1.2-4.3) and thyroid adenoma (SMR = 2.7, 95% CI 1.1-5.2). An increase in thyroid cancer risk was observed in women with thyroid adenoma (SMR = 11.7, 95% CI 1.3-42.1) but was based on only two deaths. In hyperthyroid women, statistically significant increases in the number of deaths were observed from pancreatic cancer (SMR = 2.6, 95% CI 1.4-4.3) and respiratory cancer (SMR = 2.2, 95% CI 1.3-3.5), but not breast cancer (SMR = 1.3, 95% CI 0.8-1.8). When the data were stratified by the time between the onset of thyroid symptoms and death, a nonsignificant excess number of cancer deaths was observed in hyperthyroid women who died 20 or more years after their symptoms began.(ABSTRACT TRUNCATED AT 400 WORDS)

Total cancer deaths were not increased among 2,074 women and 1,277 men who were fluoroscopically examined an average of 73 and 91 times, respectively, during lung-collapse therapy for tuberculosis (TB). Patients who did not receive this form of therapy (2,141 women and 1,418 men) and general population rates were used for comparison. All subjects were discharged alive from eight TB sanatoria in Massachusetts between 1930 and 1954; the average follow-up was 23 years. Deaths due to breast cancer were not increased among exposed females [standardized mortality ratio (SMR) = 1.0, n = 24], and SMRs greater than 2.1 could be excluded with 95% confidence. In contrast to other series, our inability to detect a breast cancer excess was likely due to lower breast doses (66 rad) and higher average ages at exposure (28 yr) and thus lower sensitivity. A deficit of lung cancer among exposed males and females was observed (SMR = 0.8, n = 26), even though increased risks have been observed among other populations exposed to similar dose levels. The estimated average lung dose was 91 rad, and SMRs greater than 1.2 for lung cancer could be excluded with 95% confidence. Overall, this study indicates that the radiation hazard of multiple low-dose exposures experienced over many years is not greater than currently accepted estimates for breast and lung cancer. For lung cancer the radiogenic risk may be less than predicted from high-dose, single-exposure studies.

Among 1,047 women fluoroscopically examined in average of 102 times during pneumothorax therapy for tuberculosis and followed up to 45 years (average = 27 yr), no increase in the total number of cancer deaths occurred when these women were compared to 717 women who received other treatments [relative risk (RR) = 0.8]. However, elevated risks of mortality from stomach cancer (RR = 2.3), rectal cancer (RR = 3.8), breast cancer (RR = 1.2), lung cancer (RR = 1.8), and leukemia (RR = 1.2) were observed, but none was statistically significant and all were based on very small numbers of deaths. These increases were balanced by decreases of genital cancer (RR = 0.2), pancreatic cancer (RR = 0.9), lymphoma (RR = 0.6), and all other cancers (RR = 0.1). Average cumulative absorbed doses were 110 rads for the lungs, 33 rads for the trunk, 13 rads for the active bone marrow, and 7 rads for the stomach. The following upper levels of excess risk could be excluded with 95% confidence: 3.5 deaths/10(6) woman-year (WY)-rad for lung cancer, 4.8 deaths/10(6) WY-rad for lymphoma, and 12 deaths/10(6) WY-rad for leukemia. These findings indicated that the carcinogenic effect of multiple low-dose X-ray exposures was not greater than that currently assumed.

Cause-specific mortality was evaluated among 2,666 men employed in the processing division of a rubber manufacturing plant. The division was divided into two sections: front processing (compounding, mixing and milling operations) and back processing (extrusion, calendering, cement mixing and rubberized fabrics operations). Mortality rates for all processing workers combined and for men in each section were compared with rates for U.S. White males or for workers employed in other divisions of the same plant. Compared with either referent group, men in the processing division had increased mortality from leukemia, emphysema, and cancers of the stomach, large intestine, and biliary passages and liver. An excess number of deaths from stomach and larger intestine cancer was found predominantly among men in the front processing section (33 observed vs. 17.7 expected deaths, based on rates in nonprocessing workers). Increased mortality from leukemia (14 observed vs. 7.3 expected) and from emphysema (22 observed vs. 11.0 expected) was present among men employed in the back processing section. Examination of mortality from these causes according to age and the year starting work, duration of employment, and years since starting work in the relevant sections of the processing division suggested that observed excesses of stomach cancer, large intestine cancer, leukemia, and emphysema among processing workers are related to occupational exposures. These results are consistent with the findings of studies of other groups of rubber workers.

Interview and record review data from 12,023 singleton deliveries were analyzed to determine the relationships between neonatal hyperbilirubinemia (10 mg/dL or greater) and maternal characteristics. Confounding variables were controlled by multiple logistic regression analysis. There was a statistically significant positive relationship between hyperbilirubinemia and low birth weight, Oriental race, premature rupture of membranes, breast-feeding, neonatal infection, use of the "pill" at time of conception, instrumental delivery, and history of first trimester bleeding. Maternal smoking and black race were negatively related to hyperbilirubinemia and statistically significant. In this study, other previously suspected etiologic factors such as epidural anesthesia, parity, use of oxytocin in labor, and white race were not associated with hyperbilirubinemia.

Mortality and morbidity from cancer among a cohort of 13,570 white male rubber workers were examined. Each man worked for at least 5 years at the Akron, Ohio, plant of the B. F. Goodrich Company. The potential period of follow-up was from January 1, 1940 to June 30, 1976. Departmental work histories were based primarily on records maintained by Local no. 5, United Rubber Workers. The occurrence of cancer was measured by death certificates and by a survey of Akron-area hospital tumor registries from 1964 to 1974. Two types of analyses were made: 1) an external comparison of mortality rates of rubber workers versus rates of U.S. white males, and 2) an internal comparison of cancer morbidity rates among persons who were employed in various work areas of the plant. Excess cases of specific cancers (observed/expected numbers) among workers in specific work areas included: stomach and intestine: rubber making (30/14.4); lung: tire curing (31/14.1), fuel cells and/or deicers (46/29.1); bladder: chemical plant (6/2.4), and tire building (16/10.7); skin cancer: tire assembly (12/1.9); brain cancer: tire assembly (8/2.0); lymphatic cancer: tire building (8/3.2); and leukemia: calendering (8/2.2), tire curing (8/2.6), tire building (12/7.5), elevators (4/1.4), tubes (4/1.6), and rubber fabrics (4/1.1). Agents that may be responsible for these excesses were considered.

We compared prior pregnancy histories of two groups of multigravidas--240 women having a pregnancy loss up to 28 weeks' gestation and 1,072 women having a term delivery. Women who had had two or more prior induced abortions had a twofold to threefold increase in risk of first-trimester spontaneous abortion, loss between 14 to 19 and 20 to 27 weeks. The increased risk was present for women who had legal induced abortions since 1973. It was not explained by smoking status, history of prior spontaneous loss, prior abortion method, or degree of cervical dilatation. No increase in risk of pregnancy loss was detected among women with a single prior induced abortion. We conclude that multiple induced abortions do increase the risk of subsequent pregnancy losses up to 28 weeks' gestation.

A retrospective cohort study was undertaken of the mortality of men exposed to carbon disulfide in the US rayon industry. The cohort consisted of 10,418 men employed between 1957 and 1979. Deaths to mid-1983 were ascertained by the Social Security Administration and the National Death Index. Total mortality in the group was slightly lower than that of the comparable US population. There was no significant difference in overall mortality between the 4,448 employees who had held jobs with the greatest potential for exposure to carbon disulfide and the 3,311 workers who had no exposure. However, there was an excess of deaths from arteriosclerotic heart disease among the potentially most heavily exposed (242 deaths observed, 195.6 expected). An excess of deaths from suicide (29 observed, 18.8 expected) was seen in only one of the four plants.

To test the hypothesis that there is a positive association between chronic alcoholism and carcinoma of the pancreas, the mortality experience of 1382 chronic alcoholics was studied. Analysis was limited to a comparison of observed and expected proportional mortality of different causes of death in the 894 whites who were known to have died. For carcinoma of the pancreas, 3 deaths were observed and 5.2 were expected. The observed/expected ratios for other causes of death, including other sites of cancer, were in accordance with prior studies.

A second follow-up was conducted of 1742 women with tuberculosis who were treated in one of two sanatoria in Massachusetts between 1930 and 1956. One hospital treated only children under the age of 17. Patient follow-up was extended from 1975 through 1980, and an additional 18 breast cancers were identified from hospital records, death certificates, and responses to a mailed questionnaire. Vital status was established for 97% of the subjects. Among 1044 women who were examined an average of 101 times with X-ray fluoroscopies during lung collapse therapy, 55 breast cancers were observed in contrast to 35.8 expected, based on incidence rates from the general population. No excess was found for 698 women treated by other means (19 observed versus 22.8 expected). Excess breast cancer risk did not appear until 15 years after initial exposure and was present at the end of 50 years of observation. Risk appeared to decrease with increasing age at exposure. Estimates of radiation dose to the breast for individuals (mean = 96 rad) were based on the most current information for the numbers of fluoroscopies, reconstruction of exposure conditions, and absorbed dose calculations. The relation between dose and breast cancer risk was consistent with linearity up to 400 rads (4 Gy). For 10-year survivors, the absolute excess risk was 5.5/1 million woman-year-rad, the excess relative risk per rad was 0.73%, and the relative risk at 100 rad was 1.7. These data indicate that a woman's lifetime risk of breast cancer is influenced by events occurring in early reproductive life, that low-dose fractionated exposures are as effective as single exposures of the same total dose in inducing breast cancer, and that risk of radiogenic breast cancer persists for many years, and perhaps for life.

Interview data from 3,214 married women having planned pregnancies and singleton deliveries who had no history of fertility treatment and who conceived more than two weeks after cessation of contraception were analyzed. The interval from cessation of contraception to conception was 13 months or greater for 24.8% of prior "pill" users vs 10.6% for former users of all other methods. As compared with former users of other methods, pill users had a notably lower monthly percentage of conceptions for the first three months and somewhat lower percentage from four to ten months. Results were not altered when potential confounding variables were controlled by logistic regression. At least 15 months of unsuccessful trials might be a more appropriate working definition of infertility for previous pill users rather than the 12-month interval generally accepted for this purpose.

The mortality experience of 13,385 tuberculosis patients treated between 1925 and 1954 in Massachusetts was determined through August 1986. Among 6,285 patients examined by X-ray fluoroscopy an average of 77 times during lung collapse therapy and followed for up to 50 yr (average = 25 yr), no increase in the total number of cancer deaths occurred [standardized mortality ratio (SMR) = 1.05, n = 424]. In contrast, the 7,100 patients treated by other means were at significant risk of dying from cancer (SMR = 1.3), especially of sites linked to cigarette smoking and alcohol use. Among the irradiated patients, estimates of mean radiation doses to the breast, lung, esophagus, and active bone marrow were 0.75, 0.84, 0.80, and 0.09 Gy, respectively. Cancers of the breast (SMR = 1.4, n = 62) and esophagus (SMR = 2.1, n = 14) were significantly increased. The risk of esophageal cancer, however, decreased with time since exposure. Lung cancer (SMR = 0.8, n = 69) and leukemia (SMR = 1.2, n = 17) were not elevated. Despite a wide range of doses to the lung, reaching over 8 Gy, there was no evidence of a dose response. Lung cancer risk also did not vary by time since exposure or age at exposure. Adjustment for smoking and the amount of lung tissue at risk did not appreciably modify these findings. These data suggest that frequent exposures to low doses of radiation over a period of several years increase the occurrence of cancer of the breast. When compared with studies of atomic bomb survivors, however, the fractionated exposures experienced by this cohort appear less effective in causing lung cancer than single exposures of the same total dose.

The association between small for gestational age (SGA) birth at term and inter-pregnancy interval was examined in a hospital cohort of 4489 multiparous women. The greatest risk of SGA birth was found in women with the shortest inter-pregnancy intervals. Even after adjusting for multiple confounding factors, women whose inter-pregnancy interval was 18 or fewer months (over one-third of women in the cohort) remained at twice the risk of giving birth to a term SGA infant when compared with women whose inter-pregnancy interval was 24-36 months. In a logistic regression analysis examining the occurrence of SGA birth in women with inter-pregnancy intervals of 36 months or less, a strong linear association was noted between these two factors. The association of term SGA birth with short inter-pregnancy interval could result from one or more physiologic factors that might act to limit fetal growth. In that case, short inter-pregnancy interval would represent a potentially preventable cause of SGA birth.

Abortion has been alleged to cause sterility. To address this issue, 1235 postabortal women, 912 women recently delivered, and 939 women from the authors' gynecology clinics were studied for as long as 3.5 years. Cumulative pregnancy rates were similar for abortion group patients, delivery group patients, and the previously pregnant clinic group. When pregnancy rates were examined by different assumptions as to entrance into follow-up, the abortion group differed only in a somewhat lower pregnancy rate after nine months, when the use of contraceptives was greater than that of the other two groups. Pregnancy rates for all three groups were influenced by age of subject, parity, race, marital and Medicaid status, and a history of urinary tract infections. Induced abortion status did not influence pregnancy rates except that women reporting three or more induced abortions had a higher pregnancy rate.

A follow-up study of 1,762 hyperthyroid women who were treated at the Massachusetts General Hospital Thyroid Unit between 1946 and 1964 was conducted. The average length of follow-up was 17.2 years. A 1978 mailing address or a death certificate was located for 92% of the women, and 88% of 1,058 living patients responded to a mail questionnaire. The standardized mortality ratio (SMR) for all causes of death was 1.3 (95% confidence interval (CI) 1.2-1.4). The standardized mortality ratios for all malignant neoplasms and for breast cancer were 0.9 (95% CI 0.7-1.1) and 1.3 (95% CI 0.8-1.9), respectively. More deaths than expected were observed from endocrine and metabolic diseases (SMR = 1.8, 95% CI 1.2-2.7), circulatory system diseases (SMR = 1.4, 95% CI 1.3-1.6), and respiratory system diseases (SMR = 1.9, 95% CI 1.3-2.6). The standardized incidence ratios (SIR) for all malignant neoplasms and for breast cancer were 0.9 (95% CI 0.8-1.1) and 1.2 (95% CI 0.9-1.5), respectively. A nonsignificant excess breast cancer risk was observed 10 years after the onset of thyroid symptoms and was present at the end of 30 years of observation. A statistically significant excess number of pancreatic cancer cases (SIR = 2.0, 95% CI 1.0-3.7) and a nonsignificant excess of brain cancer cases (SIR = 2.3, 95% CI 0.7-5.3) were observed. Eighty per cent of the women were treated with radioactive iodine. When age at treatment and year of treatment were controlled, women who were ever treated with radioactive iodine had a standardized rate ratio for breast cancer of 1.9 (95% CI 0.9-4.1), compared with those who were never treated with radioactive iodine. Women who developed hypothyroidism as a result of their treatment for hyperthyroidism did not have an increased risk of developing breast cancer (SIR = 1.1, 95% CI 0.8-1.6).

We analyzed data collected by interview and medical record review for 200 women exposed to diethylstilbestrol (DES) and 12,240 unexposed women to evaluate the relation between maternal DES exposure and outcomes of pregnancy. Low birth weight, short gestation, bleeding in the first trimester, toxemia, breech presentation and premature rupture of the membranes occurred more often among the exposed women. These relationships remained statistically significant after the use of linear regression and logistic regression analyses to control for multiple confounding factors. Both exposed women and their physicians should be aware of the possible relationship between maternal exposure to DES and late adverse outcomes of pregnancy. Close medical supervision of these women throughout pregnancy and delivery is recommended.

In an analysis of mortality among 327 employees of a rubber chemicals plant who had potential exposure to acrylonitrile, nine deaths from lung cancer were found in comparison to 5.9 expected based on mortality rates for U.S. white males and 4.7 expected based on mortality rates for other rubber workers from the same city. The excess was greatest among men who worked five through 14 years and who died 15 or more years after starting work in the plant (four deaths observed, 0.8 expected).