Radiation-associated lung cancer: a comparison of the histology of lung cancers in uranium miners and survivors of the atomic bombings of Hiroshima and Nagasaki

A binational panel of Japanese and American pulmonary pathologists reviewed tissue slides of lung cancer cases diagnosed among Japanese A-bomb survivors and American uranium miners and classified the cases according to histological subtype. Blind reviews were completed on slides from 92 uranium miners and 108 A-bomb survivors, without knowledge of population, sex, age, smoking history, or level of radiation exposure. Consensus diagnoses were obtained with respect to principal subtype, including squamous-cell cancer, small-cell cancer, adenocarcinoma, and less frequent subtypes. The results were analyzed in terms of population, radiation dose, and smoking history. As expected, the proportion of squamous-cell cancer was positively related to smoking history in both populations. The relative frequencies of small-cell cancer and adenocarcinoma were very different in the two populations, but this difference was accounted for adequately by differences in radiation dose or, more specifically, dose-based relative risk estimates based on published data. Radiation-induced cancers appeared more likely to be of the small-cell subtype, and less likely to be adenocarcinomas, in both populations. The data appeared to require no additional explanation in terms of radiation quality (alpha particles vs gamma rays), uniform or local irradiation, inhaled vs external radiation source, or other population difference.     

Comparison of breast cancer incidence in the Massachusetts tuberculosis fluoroscopy cohort and in the Japanese atomic bomb survivors

Breast cancer has occurred in excess among women exposed briefly to atomic bomb radiation and among those exposed repeatedly over many years to medical radiation for tuberculosis (TB). The excess relative risk of breast cancer incidence in the Japanese atomic bomb survivors, however, is significantly higher (two-sided P = 0.04) than that in the Massachusetts TB fluoroscopy patients. The best estimate of the ratio between the excess relative risk coefficients for the Japanese and Massachusetts cohorts is 2.11 (95% CI 1.05, 4.95). However, this higher relative excess risk is attributable to the lower baseline risk of breast cancer among Japanese women compared with the Massachusetts women, and the excess absolute breast cancer risks in the two data sets are statistically indistinguishable (two-sided P = 0.32). The best estimate of the ratio between the excess absolute risk coefficients among Japanese and Massachusetts women is 0.73 (95% CI 0.41, 1.44). After childhood exposures, an early onset of radiation-induced breast cancer was seen among Japanese atomic bomb survivors but not among the Massachusetts women. There are some indications (two-sided P = 0.04) of differences in the patterns of risk over time since exposure between these groups exposed in childhood. However, in general there are no marked differences between the Massachusetts and Japanese data sets in the age and time distribution of risk of radiation-induced breast cancer. These data provide little evidence for a reduction of breast cancer risk after fractionated irradiation.     

Some aspects of measurement error in explanatory variables for continuous and binary regression models

A simple form of measurement error model for explanatory variables is studied incorporating classical and Berkson cases as particular forms, and allowing for either additive or multiplicative errors. The work is motivated by epidemiological problems, and therefore consideration is given not only to continuous response variables but also to logistic regression models. The possibility that different individuals in a study have errors of different types is also considered. The relatively simple estimation procedures proposed for use with cohort data and case-control data are checked by simulation, under the assumption of various error structures. The results show that even in situations where conventional analysis yields slope estimates that are on average attenuated by a factor of approximately 50 per cent, estimates obtained using the proposed amended likelihood functions are within 5 per cent of their true values. The work was carried out to provide a method for the analysis of lung cancer risk following residential radon exposure, but it should be applicable to a wide variety of situations.     

Exposure-response analysis of risk of respiratory disease associated with occupational exposure to chrysotile asbestos

OBJECTIVES: To evaluate alternative models and estimate risk of mortality from lung cancer and asbestosis after occupational exposure to chrysotile asbestos. METHODS: Data were used from a recent update of a cohort mortality study of workers in a South Carolina textile factory. Alternative exposure-response models were evaluated with Poisson regression. A model designed to evaluate evidence of a threshold response was also fitted. Lifetime risks of lung cancer and asbestosis were estimated with an actuarial approach that accounts for competing causes of death. RESULTS: A highly significant exposure-response relation was found for both lung cancer and asbestosis. The exposure-response relation for lung cancer seemed to be linear on a multiplicative scale, which is consistent with previous analyses of lung cancer and exposure to asbestos. In contrast, the exposure-response relation for asbestosis seemed to be nonlinear on a multiplicative scale in this analysis. There was no significant evidence for a threshold in models of either the lung cancer or asbestosis. The excess lifetime risk for white men exposed for 45 years at the recently revised OSHA standard of 0.1 fibre/ml was predicted to be about 5/1000 for lung cancer, and 2/1000 for asbestosis. CONCLUSIONS: This study confirms the findings from previous investigations of a strong exposure-response relation between exposure to chrysotile asbestos and mortality from lung cancer, and asbestosis. The risk estimates for lung cancer derived from this analysis are higher than those derived from other populations exposed to chrysotile asbestos. Possible reasons for this discrepancy are discussed.     

Genetic counseling in autism and pervasive developmental disorders

Although alcohol intake and hepatitis B and C virus (HBV and HCV) infections are the major determinants of liver cirrhosis (LC) in western countries, the joint effect of these factors on LC risk has not yet been adequately studied. Data from three case-control studies performed in Italy were used. Cases were 462 cirrhotic patients admitted to Hospitals for liver decompensation. Controls were 651 inpatients admitted for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Three approaches were used to explore the interaction structure. The Breslow and Storer parametric family of relative risk functions showed that an intermediate structure of interaction from additive to multiplicative was the most adequate one. The Rothman synergism index showed that the interaction structure between LDAI and viral status differed significantly from the additive model in particular for high levels of alcohol intake. When multiple regression additive and multiplicative models were compared after adjustment for the known confounding variables. a trend of the interaction structure towards the multiplicative model was observed at increasing levels of consumption. Better methods are needed for assessing mixed interaction structures in conditions characterized by multifactorial etiologies like cirrhosis of the liver.     

Carcinogenic risk coefficients at environmental levels of radon exposures: a microdosimetric approach

We report a microdosimetric-based evaluation of the effects of domestic exposure to radon. The risk coefficients obtained here are based on the microdosimetry of radon progeny alpha particles, on a function q(y) for in vivo radiogenic neoplasia, and on scaling A-bomb results (epidemiology + microdosimetry) to radon exposure. We do not use miner data, nor do we invoke such notions as quality factors, dose equivalent or equivalent dose. With basal cells as targets our estimated risk coefficients are in good agreement with the miner data, and thus a quality factor of about 20 (as suggested by ICRP 60) is not unreasonable. However, if we take as targets the secretory cells our risk coefficients are twice as large as those reported by BEIR-IV. The main uncertainty in these estimates remains the dosimetric model.     

Reliability, Risk, and Uncertainty Analysis Using Generic Expectation Functions

In engineering design and analysis, mathematical models that generally involve a number of uncertain parameters are frequently employed for decision making. Over the years, a number of techniques have been developed to quantify model output uncertainty contributed by uncertain input parameters. Typically, the methods that are easy to apply may give inaccurate estimates of model output uncertainty. Other methods that reliably produce very accurate results are either difficult to apply or require intensive computational effort. This paper describes the development of generic expectation functions as a function of means and coefficients of variation of input random variables. The generic expectation functions are straightforward to develop, and apply to problems related to reliability, risk, and uncertainty analysis. Several expectation functions based on commonly used probability distributions have been developed. Using them, any order of moment can be estimated exactly. It is found that if exact moments of the model output are available, one can find a good estimate of reliability, risk, and uncertainty of a system without knowing its model output distribution exactly. This technique is applicable when an output variable is a function of several independent random variables in multiplicative, additive, or combined (multiplicative and additive) forms. A practical example is presented to demonstrate the application of generic expectation functions.     

Breast cancer risk from low-dose exposures to ionizing radiation: results of parallel analysis of three exposed populations of women

Breast cancer incidence data were analyzed from three populations of women exposed to ionizing radiation: survivors of the Hiroshima and Nagasaki atomic bombs, patients in Massachusetts tuberculosis sanitoria who were exposed to multiple chest fluoroscopies, and patients treated by X-rays for acute postpartum mastitis in Rochester, New York. Parallel analyses by radiation dose, age at exposure, and time after exposure suggested that risk of radiation-induced cancer increased approximately linearly with increasing dose and was heavily dependent on age at exposure; however, the risk was otherwise remarkably similar among the three population, at least for age 10-40 years at exposure, and followed the same temporal pattern of occurrence as did breast cancer incidence in nonexposed women of similar ages.     

Population attributable fraction estimation for established breast cancer risk factors: considering the issues of high prevalence and unmodifiability

Established breast cancer risk factors, in addition to being relatively unmodifiable, are highly prevalent among US women. Previous reports of population attributable fraction for the established risk factors have used definitions that resulted in 75-100% of women in the source population labeled exposed. The practical value of such estimates has not been discussed; further, the estimates have frequently been misinterpreted. In the context of examining the interpretation and public health value of such estimates, the authors demonstrate the sensitivity of the population attributable fraction to changes in exposure cutpoints. They use data from the Carolina Breast Cancer Study, a case-control study of breast cancer conducted in North Carolina between 1993 and 1996. For the four established risk factors (menarche before age 14 years, first birth at age 20 years or later/nulliparity, family history of breast cancer, and history of benign breast biopsy), the estimated population attributable fraction was 0.25 (95% confidence interval 0.06-0.48). Over 98% of the source population was exposed to at least one of these risk factors. The population attributable fraction estimate was reduced to 0.15 when more restrictive definitions of early menarche (less than age 12 years) and late age at first full-term pregnancy (30 years or more) were used (proportion exposed, 0.62). Population attributable fractions for established breast cancer risk factors probably have little public health value because of both the high proportions exposed and the relative unmodifiability of the risk factor distributions.     

Exercise and breast cancer: review and critical analysis of the literature

Breast cancer is one of the leading causes of cancer and cancer mortality among Canadian women. Based on the current incidence rates, the National Cancer Institute of Canada has estimated that one in 10 women will develop breast cancer during her lifetime. In an effort to control this disease, various prevention strategies have been proposed. One promising strategy involves the promotion of exercise in healthy women. It has been hypothesized that exercise may protect against breast cancer by influencing regularity of ovulatory cycles, by changing body fat composition, or by enhancing natural immunity. In this paper both the epidemiological and experimental evidence that speaks to a protective effect of exercise is reviewed. Although there are several biologically plausible mechanisms for the association, the existing epidemiological and experimental data are inconclusive due to the small number of studies and their methodological insufficiencies. However, given the enormous potential benefit of even a small protective effect of exercise, further studies designed to address the relationship between exercise and breast cancer risk are warranted.     

Early cancer detection programmes for women at high risk for breast and ovarian cancer: a proposal of practical guidelines

Women from families with multiple breast and/or ovarian cancers may be at increased risk to develop breast/ovarian cancer themselves. Due to personal experience with family members having these diseases they are anxious and ask for specific prophylactic measurements or treatment. The detection of two susceptibility genes, BRCA1 and BRCA2, has given insight into the genetic background of part of the familial breast/ovarian cancer syndromes. This has led to an increased demand in genetic counselling, testing, and early cancer detection programmes. Prospective data from early cancer detection programmes in this high risk population are yet not available. Based on data from epidemiological risk studies, breast and ovarian screening programmes and follow up data from breast cancer trials recommendations for an early cancer detection programme have been summarized. At the present these recommendations are tested in a prospective trial.     

Sexual functioning and intimacy in African American and white breast cancer survivors: a descriptive study

This study examines ethnic differences in sexual socialization and attitudes, sexual history and current practices, and the effects of treatment in 147 African American and White breast cancer survivors. Sex-related research in younger healthy populations has shown that cultural values associated with ethnicity influence sexual functioning, but small numbers of African American participants in previous research in breast cancer survivors has limited what we know about that population. In this study, there were few differences between the 2 ethnic groups in a predominantly well-educated, high-income, highly functional sample. However, African American women were significantly less likely to be comfortable with and to practice oral sex, self-touching, and masturbatory behaviors. White women were more likely to report that breast cancer had a negative impact on their sex lives. These differences in sexual repertoire and functioning should be noted by health care practitioners treating the sexual sequelae of breast cancer treatment.     

Nutritional factors and colon cancer

During the last 2 decades, substantial progress has been made in understanding the relationship between dietary constituents and the development of colon cancer in man. Unlike studies of cancer among smokers and nonsmokers, nutritional epidemiologic studies are confronted with the inherent difficulty of assessing reasonably precise exposures. The lack of consistency between international correlation studies and case-control studies does not necessarily negate a dietary etiology of colon cancer because these inconsistencies may have arisen, at least in part, from methodological limitations. Some of these deficiencies in epidemiological studies of diet and cancer have been corrected; recent case-control studies demonstrated that high dietary fat is a risk factor for colon cancer development and that an overall increase in intake of foods high in fiber might decrease the risk for colon cancer. The results of epidemiologic studies may be assumed to present conservative estimates of the true risk for cancer associated with diet. The populations with high incidences of colon cancer are characterized by high consumption of dietary fat, which may be a risk factor in the absence of factors that are protective, such as whole-grain cereals and of other high fiber. Laboratory-animal model studies have shown that certain dietary lipids and fibers influence tumorigenesis in the colon. The data of metabolic epidemiological and laboratory-animal model studies are sufficiently convincing with respect to the enhancement of colon cancer by type of fat and protection by certain dietary fibers.     

Development of a quantitative risk assessment model for Salmonella enteritidis in pasteurized liquid eggs

Since Kraepelin delineated dementia praecox as a disease entity construct, epidemiological studies conducted since the beginning of the century have produced remarkably consistent estimates of its prevalence, incidence and lifetime risk across various populations and geographic areas. A similar pattern emerged from the WHO ten-country study on first-contact incidence of schizophrenia. The diagnostic concept of dementia praecox originally used by Kraepelin and that of schizophrenia employed in the WHO studies were found to overlap extensively, indicating continuity over time. However, the findings of a similar incidence of schizophrenia in diverse populations and across time periods are unusual for a multifactorial disease and are compatible with at least two alternative interpretations that have different implications for the search for genetic and environmental causes of the disorder.     

Trends in breast cancer screening in Missouri from 1987 to 1995, and predictions for the years 2000 and 2010

BACKGROUND: Breast cancer is a major cause of morbidity and mortality in the United States (U.S.) and Missouri. In 1992, 3,915 new breast cancer cases were diagnosed and in 1995, 1,006 deaths from breast cancer were reported in Missouri. Although breast cancer incidence has increased in Missouri in the past 20 years, there are indications that early detection has also increased during the same period. Knowledge about which segments of the population have experienced the greatest increase in mammography screening rates helps in planning and implementation of breast cancer control programs at the state level. OBJECTIVES: Examine the prevalence and trends of lifetime mammography and 2-year mammography compliance in Missouri by age, race, and education from 1987 to 1995 and make predictions for the years 2000 and 2010. METHODS: We used data from the Missouri Behavioral Risk Factor Surveillance System (BRFSS), 1987 to 1995, to estimate the prevalence of ever having had a mammogram and compliance with mammography screening guidelines within two years by race, age, and education status among Missouri women over age 18. Using linear models, we regressed breast cancer screening prevalence estimates on time to obtain trends and predictions. RESULTS: Overall, African-American women were more likely to have had a lifetime mammogram than white women. However, we found a steady increase in the prevalence of ever having had a mammogram for all groups of women defined by age and education status, except among African Americans. Increase in the prevalence of ever having had a mammogram was much higher in women age 50 and older and slightly higher among women with a high school education or less. The average prevalence of 2-year mammography screening compliance was about 60% for all groups, a rate which did not significantly change between 1987 and 1995. By the year 2000, white women will have mammography rates equal to or higher than African-American women, and the majority of all women age 50 and older (98.3% to 100%) will have had a lifetime mammogram. CONCLUSION: Missouri target populations are predicted to attain Year 2000 National Health Objectives concerning lifetime mammography. Current efforts should be continued in order to maintain levels of mammography, particularly among African-American women.     

Female sex hormones increase the risk of breast cancer

The incidence of breast cancer in women in increasing, partly due to changes in age distribution in the population, and partly due to a real increase in risk. Changes in family patterns may, to some extent, explain the increased risk since giving birth to a first child late in life and bearing few children both increase the risk of breast cancer. The influence of female sex steroids on the breast plays a central role, but the biological mechanism is not clearly understood. There is a certain amount of risk involved in using hormonal medication (oral contraceptives or postmenopausal hormone replacement), but on ceasing to take the medication, risk will revert to the expected rate within a few years. Future epidemiological research on breast cancer will concentrate on events occurring during hormonally potent phases of life, such as growth and development during the fetal period, and sexual and somatic maturation during adolescence. Until now only modest interest has been shown in researching these two particular phases, but both may be important for the natural course of breast cancer.     

Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies

The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (> 10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to > 1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk about 1.10 Gy.