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J D Boice

Publications and source records attributed to J D Boice.

At least 19 recordsLinked to original sources

Sex ratio among offspring of childhood cancer survivors treated with radiotherapy.

It has been postulated that paternal gonadal exposure would increase the sex ratio by inducing X-chromosomal dominant lethals but that maternal gonadal exposure would decrease the sex ratio by inducing recessive sex-linked lethals. We therefore evaluated the sex ratio (male-to-female ratio) of children born to survivors of childhood cancers in Denmark. Children with cancer were identified from the Danish Cancer Registry from 1943 to 1996 and their offspring from the Central Population Registry. Radiation treatments were determined from records within the Cancer Registry and gonadal radiation exposures were estimated based on the cancer being treated and the likely proximity of the radiation fields to the gonads. Overall, 1100 survivors of childhood cancer became the parents of 2130 children. The sex ratio for male (0.99) and female (1.00) cancer survivors was similar and did not differ significantly from the Danish population (1.06). Radiotherapy did not influence the sex ratio of the children of either male or female survivors, and there was no evidence for dose-related changes over categories of estimated dose to parental gonads. We saw no consistent association between the sex ratio and the interval between cancer diagnosis of the parent and birth of the child. This nationwide study provides no support for the hypothesis that radiation exposure to the gonads results in an inherited genetic effect that would be manifested by a change in the sex ratio of children born after exposure. It may be, however, that sex ratio alterations are not a good or even a valid indicator of possible genetic effects in humans.

Child↗

Lung cancer after treatment for Hodgkin's disease: focus on radiation effects.

Aspects of radiation-induced lung cancer were evaluated in an international study of Hodgkin's disease. The study population consisted of 227 patients with lung cancer and 455 matched controls. Unique features included dose determinations to the specific location in the lung where each cancer developed and quantitative data on both chemotherapy and tobacco use obtained from medical records. The estimated excess relative risk (ERR) per Gy was 0.15 (95% CI: 0.06-0.39), and there was little evidence of departure from linearity even though lung doses for the majority of Hodgkin's disease patients treated with radiotherapy exceeded 30 Gy. The interaction of radiation and chemotherapy that included alkylating agents was almost exactly additive, and a multiplicative relationship could be rejected (P = 0.017). Conversely, the interaction of radiation and smoking was consistent with a multiplicative relationship, but not with an additive relationship (P < 0.001). The ERR/Gy for males was about four times that for females, although the difference was not statistically significant. There was little evidence of modification of the ERR/Gy by time since exposure (after a 5-year minimum latent period), age at exposure, or attained age. Because of the very high radiation doses received by Hodgkin's disease patients and the immunodeficiency inherent to this lymphoma and that associated with chemotherapy, generalizing these findings to other populations receiving considerably lower doses of radiation should be done cautiously.

Adult↗

Mobile phones and malignant melanoma of the eye.

Recently a four-fold increase in the risk of malignant melanoma of the eye was associated with the use of radiofrequency transmitting devices, including mobile phones in Germany. We contrasted the incidence rates of this rare cancer with the number of mobile phone subscribers in Denmark. We observed no increasing trend in the incidence rate of melanoma, which was in sharp contrast to the exponentially increasing number of mobile phone subscribers starting in the early 1980s. Our study provides no support for an association between mobile phones and ocular melanoma.

Cohort Studies↗

Cancer in siblings of children with cancer in the Nordic countries: a population-based cohort study.

BACKGROUND: In some rare inherited disorders such as Li-Fraumeni syndrome, relatives of children with cancer are at increased risk of cancer. We aimed to assess relations between childhood cancer and sibling risk, and evaluate the influence of recessive conditions in cancer causation. METHODS: We did a population-based cohort study in the Nordic countries of 42277 siblings of 25605 children with cancer. Children with cancer were identified from records in the five Nordic cancer registries, and their siblings from nationwide population registries. Cancers in siblings were documented through record linkage with cancer registries and compared with national incidence rates. We also assessed cancer incidence in parents to identify familial cancer syndromes. FINDINGS: 284.2 cancers were expected in siblings, whereas 353 were diagnosed (standardised incidence ratio 1.24 95% CI 1.12-1.38). Risk ratios for siblings were highest in the first decade of life (2.59, 1.89-3.46). We excluded 56 families with genetic syndromes linked to cancer, which reduced this ratio from 1.7 to 1.0 (0.7-1.3) for siblings younger than 20 years, and from 1.3 to 1.0 (0.8-1.3) for those aged 20-29 years. We found no new patterns of familial cancer that indicated inherited susceptibility, or evidence that recessive conditions might contribute to cancers not explained by syndromes. 40% of cancers in siblings that occurred before age 20 years could be attributed to known genetic factors, whereas 60% remained unexplained. INTERPRETATION: Apart from rare cancer syndromes, paediatric cancer is not an indicator of increased cancer risk in siblings.

Adolescent↗

Breast cancer risk in relation to amount of tissue removed during breast reduction operations in Sweden.

BACKGROUND: Women who undergo breast reduction operations have substantially lowered risks of breast cancer, and the reasons remain unclear. The current investigation attempted to assess whether the reduction in breast cancer risk was related directly to the amount of breast tissue removed. METHODS: Medical record retrieval was attempted for 161 breast cancer patients in a Swedish cohort of 31,910 women who had had breast reduction surgery and for 483 women who had not developed breast cancer. Information on amount of breast tissue removed was abstracted along with other factors that influence breast cancer risk. Odds ratios of developing breast cancer were calculated based on amount of breast tissue removed. RESULTS: The amount of tissue removed was a significant predictor of risk, as subjects in the highest quartile of tissue removal had a significantly lower risk than those in the lowest quartile. Considering the total amount of tissue removed (both breasts), subjects with > or = 1600 versus < 800 grams removed had an odds ratio (OR) of 0.24 [95% confidence interval (CI) 0.1-0.5]. This relation persisted after adjustment for other breast cancer risk factors and was apparent within every subgroup examined. CONCLUSIONS: The finding that breast cancer risk was reduced in proportion to the amount of tissue removed should be reassuring to women who are considering breast reduction procedures and to women who are electing to have bilateral total prophylactic mastectomies because of a strong genetic predisposition.

Adolescent↗

Cancer in patients with ataxia-telangiectasia and in their relatives in the nordic countries.

BACKGROUND: Epidemiologic studies of the families of patients with ataxia-telangiectasia (A-T), a recessive genetic neurologic disorder caused by mutation of the ATM gene, suggest that heterozygous carriers of an ATM mutation are at increased risk of cancer. A population-based study of cancer incidence in A-T families with unbiased selection and tracing of relatives would confirm this hypothesis. METHODS: We conducted a study in the Nordic countries of 1218 blood relatives of 56 A-T patients from 50 families. The relatives were identified from population registries, and the occurrence of cancer was determined from cancer registry files in each country and compared with national incidence rates. All statistical tests were two-sided. RESULTS: Among the 56 patients with A-T, we observed six cases of cancer (four leukemias and two non-Hodgkin's lymphomas) compared with 0.16 expected, yielding a standardized incidence ratio (SIR) of 37 (95% confidence interval [CI] = 13 to 80). Among the 1218 relatives, 150 cancers were recorded, with 126 expected (SIR = 1.19; 95% CI = 1.01 to 1.40). Invasive breast cancer occurred in 21 female relatives of A-T patients (SIR = 1.54; 95% CI = 0.95 to 2.36), including five of the 50 mothers (all of whom are obligate ATM mutation carriers) (SIR = 7.1; 95% CI = 2.3 to 17). Relatives who were less likely to be carriers of a mutant ATM allele had no increase or only a modest, statistically nonsignificant increase in the risk of breast cancer. There was no evidence of increased risk for cancer at any other site. CONCLUSIONS: We confirmed the previously recognized high risk of lymphoma and leukemia in A-T patients. Our data are also consistent with an increased risk of breast cancer among blood relatives of A-T patients. The epidemiologic findings suggest, however, that, even if ATM mutations are responsible for some breast cancer cases, ATM is a relatively weak genetic risk factor for the disease.

Adult↗

Radiation and breast carcinogenesis.

With the possible exception of radiation-induced leukemia, more is known about radiation-induced breast cancer than any other malignancy. Fourteen cohort studies have provided quantitative information on the level of risk following a wide range of doses in different populations around the world. Comprehensive studies have been conducted in Canada, Germany, Japan, Sweden and other Nordic countries, the United Kingdom, and the USA [Table I in text]. Key features are the linearity in the dose response (i.e., a straight line adequately fits the observed data), and the effect modification of age at exposure (i.e., risk is inversely related to exposure age and exposures past the menopausal ages appear to carry a very low risk); and the minimal effect of fractionating dose on subsequent risk. A recent combined analysis of almost 78,000 women and 1,500 breast cancer cases from eight cohorts confirmed the downturn in risk at the highest dose levels (related in part to the killing of cells rather than transformation) and that fractionation of dose has little influence on risk, at least on an absolute scale. It is not known whether persons predisposed to cancer are at enhanced risk of radiation-induced breast cancer from low-dose exposures, although this seems unlikely. New data on the effects of high doses following childhood exposures will be forthcoming from long-term studies of the survivors of childhood cancer.

Age Factors↗

Errors in TCE analysis.

Comments on Wartenberg D, Reyner D, Scott CS's article "richloroethylene and cancer: epidemiologic evidence." Environ Health Perspect 108(suppl 2):161-176 (2000)

Air Pollutants, Occupational↗

Mortality after cerebral angiography with or without radioactive Thorotrast: an international cohort of 3,143 two-year survivors.

There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P < 0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P < 0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with >20 ml Thorotrast and approached 50%.

Adult↗

Intrauterine exposure to diagnostic X rays and risk of childhood leukemia subtypes.

The relationship between childhood leukemia and prenatal exposure to low-dose ionizing radiation remains debatable. This population-based case-control study investigated the association between prenatal exposure to diagnostic X-ray examinations (for different types of examinations and at different stages of pregnancy) and the risk of childhood lymphatic and myeloid leukemia. All children born and diagnosed with leukemia between 1973-1989 in Sweden (578 lymphatic and 74 myeloid) were selected as cases, and each was matched (by sex and year of birth) to a healthy control child (excluding Down's syndrome). Exposure data were abstracted blindly from all available medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression. It was found that prenatal X-ray examinations resulting in direct fetal exposure were not associated with a significant overall increased risk for childhood leukemia (OR = 1.11, 95% CI 0.83-1.47), for lymphatic leukemia (OR = 1.04, 95% CI 0.77-1.40), or for myeloid leukemia (OR = 1.49, 95% CI 0.48-4.72). There was little evidence of a dose response or variation in risk by trimester of exposure or age at diagnosis. Thus X-ray examinations performed during pregnancy in the 1970s and 1980s in Sweden did not affect the risk of childhood leukemia discernibly.

Adolescent↗

Treatment-associated leukemia following testicular cancer.

BACKGROUND: Men with testicular cancer are at an increased risk of leukemia, but the relationship to prior treatments is not well characterized. The purpose of our study was to describe the risk of leukemia following radiotherapy and chemotherapy for testicular cancer. METHODS: Within a population-based cohort of 18 567 patients diagnosed with testicular cancer (from 1970 through 1993), a case-control study of leukemia was undertaken. Radiation dose to active bone marrow and type and cumulative amount of cytotoxic drugs were compared between 36 men who developed leukemia and 106 matched control patients without leukemia. Conditional logistic regression was used to estimate the relative risk of leukemia associated with specific treatments. All P values are two-sided. RESULTS: Radiotherapy (mean dose to active bone marrow, 12.6 Gy) without chemotherapy was associated with a threefold elevated risk of leukemia. Risk increased with increasing dose of radiation to active bone marrow (P for trend =.02), with patients receiving radiotherapy to the chest as well as to the abdominal/pelvic fields accounting for much of the risk at higher doses. Radiation dose to active bone marrow and the cumulative dose of cisplatin (P for trend =.001) were both predictive of excess leukemia risk in a model adjusted for all treatment variables. The estimated relative risk of leukemia at a cumulative dose of 650 mg cisplatin, which is commonly administered in current testicular cancer treatment regimens, was 3.2 (95% confidence interval = 1.5-8.4); larger doses (1000 mg) were linked with statistically significant sixfold increased risks. CONCLUSIONS: Past treatments for testicular cancer are associated with an increased risk of leukemia, with evidence for dose-response relationships for both radiotherapy and cisplatin-based chemotherapy. Statistically nonsignificant excesses are estimated for current radiotherapy regimens limited to the abdomen and pelvis: Among 10 000 patients given a treatment dose of 25 Gy and followed for 15 years, an excess of nine leukemias is predicted; cisplatin-based chemotherapy (dose, 650 mg) might result in 16 cases of leukemia. The survival advantage provided by current radiotherapy and chemotherapy regimens for testicular cancer far exceeds the small absolute risk of leukemia.

Adult↗

Mortality among Catholic nuns certified as radiologic technologists.

BACKGROUND: Several studies have shown that Catholic nuns have a different mortality experience than women of similar age in the general population. We had a unique opportunity to evaluate mortality patterns of nuns identified in an occupational study of nearly 145,000 radiologic technologists (73% female). METHODS: A total of 1,103 women were classified as nuns based on their titles of "Sister" or "SR". Their mortality experience was compared to other female radiologic technologists and to U.S. white females. RESULTS: Five hundred eighty-three nuns (53%) were deceased as of January 1, 1995. Compared to other technologists, nuns were at significantly increased risk of dying from all causes (Standardized mortality ratio (SMR)=1.1; 95% Confidence interval (CI)=1.0-1.2, stomach cancer (SMR=2.7; 95% CI=1.2-5.4), diabetes (SMR=2.2; 95% CI=1.0-4.1), ischemic heart disease (SMR=1.2; 95% CI=1.1-1.4), all digestive diseases (SMR=2.0; 95% CI=1.3-3.0), and gastric and duodenal ulcers (SMR=8.3; 95% CI=2.3-21.3). In contrast, we observed a significant deficit in lung cancer (SMR=0.5; 95% CI=0.2-0.9), no deaths from cervical cancer, and a breast cancer risk 10% lower than expected (SMR=0.9; 95% CI=0.6-1.3). When compared to U.S. females, nuns experienced significantly reduced mortality from all causes (SMR=0.8; 95% CI=0.7-0.9), cervical cancer (SMR=0.0; 95% CI=0.0-0.7), all endocrine, metabolic and nutritional diseases (SMR=0.5; 95% CI=0.3-0.9), all circulatory diseases (SMR=0.7; 95% CI=0.7-0.8) including ischemic heart disease and cerebrovascular disease, and all respiratory diseases (SMR=0.5; 95% CI=0.3-0.8), and a nearly significant deficit of diabetes (SMR=0.6; 95% CI=0.3-1.0). In contrast, nuns had an almost 3-fold greater risk of tuberculosis (SMR=2.9; 95% CI=1.4-5.3) and a 20% excess of breast cancer (SMR=1. 2; 95% CI=0.8-1.7). The breast cancer excess was concentrated among nuns first certified before 1940 (SMR=2.0; CI=1.3-3.0), when radiation doses were possibly the highest, but the risk did not increase with increasing length of certification. CONCLUSIONS: Compared with the general population, the mortality experience of nuns was favorable and reflected the "healthy worker effect" commonly seen in occupational studies. Patterns observed for breast and cervical cancer possibly indicate differences in reproductive and sexual activities associated with belonging to a religious order. The possibility of a radiation-related excess for breast cancer among nuns certified before 1940 cannot be completely discounted, although there was no dose-response relationship with a surrogate measure of exposure (number of years certified). When their mortality experience was compared with other radiologic technologists, the influence of lifestyle factors was not apparent. Am. J. Ind. Med. 37:339-348, 2000. Published 2000 Wiley-Liss, Inc. dagger

Adult↗

Exposure assessment for a large epidemiological study of aircraft manufacturing workers.

Methods were developed to assess exposure to a wide variety of chemicals for nearly 80,000 workers involved in manufacturing aircraft since 1928. The facilities, now closed, consisted of four major plants, over 200 buildings, and a changing workforce during 60 years of operation. To access chemical exposures by specific jobs and calendar years, we reviewed complete work histories, examined detailed job descriptions available going back to 1940, interviewed long-term employees, conducted walk-through visits of aircraft manufacturing plants, reviewed comprehensive environmental assessment reports and industrial hygiene surveys on the facilities, and built on experience gained in previous studies of the aircraft industry. Using computer-based imaging systems, we examined and evaluated the complete work histories found on service record cards for the cohort and abstracted detailed information on all jobs held among the factory workers who had been employed for at least one year. Jobs were classified into one of three exposure categories related to the use of specific chemicals: routine, intermittent, and none, and these classifications were subsequently used in the epidemiological analyses. The approach to exposure assessment began with the most general categorization of employees (i.e., all workers) and then became progressively more specific, that is, factor workers, job families (similar activities), job titles, and jobs with chemical usage (exposure potential). Because exposure surveys were limited or absent during the early years of plant operations, we did not assign quantitative measures of exposure to individual job activities. Instead, we used as our exposure metric, the length of time spent in jobs with potential exposure to the chemical. Important occupational exposures included chromate-containing compounds such as used in paint primers, trichloroethylene and perchloroethylene used as vapor-state degreasing solvents, and a broad range of other solvents.

Adult↗

Epidemiologic studies of pilots and aircrew.

During flight, pilots and cabin crew are exposed to increased levels of cosmic radiation which consists primarily of neutrons and gamma rays. Neutron dosimetry is not straightforward, but typical annual effective doses are estimated to range between two and five mSv. Higher dose rates are experienced at the highest altitudes and in the polar regions. Mean doses have been increasing over time as longer flights at higher altitudes have become more frequent. Because there are so few populations exposed to neutrons, studies of airline personnel are of particular interest. However, because the cumulative radiation exposure is so low, statistical power is a major concern. Further, finding an appropriate comparison group is problematic due to selection into these occupations and a number of biases are possible. For example, increased rates of breast cancer among flight attendants have been attributed to reproductive factors such as nulliparity and increased rates of melanoma among pilots have been attributed to excessive sun exposure during leisure time activities. Epidemiologic studies conducted over the last 20 y provide little consistent evidence linking cancer with radiation exposures from air travel.

Aircraft↗

Breast cancer following breast reduction surgery in Sweden.

Women undergoing breast reduction surgery have been reported to be at low subsequent risk of breast cancer, especially when the surgery is performed after age 40. To evaluate the age and time-related patterns of cancer risk following surgical removal of breast tissue, we identified 31,910 women who underwent breast reduction surgery from 1965 to 1993 in Sweden using hospital discharge register data. There were 19,975 women (63 percent) under age 40 at surgery. Linkages with Swedish registries for cancer, death, and emigration were based on unique national registration numbers assigned to each Swedish resident. Cancer incidence was contrasted with that expected in the general population based on age- and calendar year-specific data from the nationwide cancer registry. Overall, 161 incident breast cancers were identified during 238,765 person-years of observation (mean, 7.5 years) compared with 223.9 expected (standardized incidence ratio = 0.72; 95 percent confidence interval = 0.61 to 0.84). The reduction in risk of breast cancer was most pronounced for women whose operations were performed after age 50 (SIR = 0.57) and for those followed for more than 5 years (SIR = 0.68). Among women operated on before age 40, risk was nonsignificantly elevated within the first 5 years after surgery (SIR = 1.47; 95 percent CI = 0.89 to 2.30) but tended to be reduced thereafter (SIR = 0.80; 95 percent CI = 0.55 to 1.13). The magnitude of the reduction in risk thus appears directly related to age at surgery. Women followed for an average of 7.5 years after bilateral breast reduction surgery, were at a statistically significant 28 percent decreased risk of breast cancer. The current study is thus consistent with a protective effect following partial removal of breast glandular tissue.

Adolescent↗