Biomedical subjects

Dale L Preston

Publications and source records attributed to Dale L Preston.

10 recordsLinked to original sources

PubMed2006

Dose estimation for atomic bomb survivor studies: its evolution and present status.

In the decade after the bombings of Hiroshima and Nagasaki, several large cohorts of survivors were organized for studies of radiation health effects. The U.S. Atomic Bomb Casualty Commission (ABCC) and its U.S./Japan successor, the Radiation Effects Research Foundation (RERF), have performed continuous studies since then, with extensive efforts to collect data on survivor locations and shielding and to create systems to estimate individual doses from the bombs' neutrons and gamma rays. Several successive systems have been developed by extramural working groups and collaboratively implemented by ABCC and RERF investigators. We describe the cohorts and the history and evolution of dose estimation from early efforts through the newest system, DS02, emphasizing the technical development and use of DS02. We describe procedures and data developed at RERF to implement successive systems, including revised rosters of survivors, development of methods to calculate doses for some classes of persons not fitting criteria of the basic systems, and methods to correct for bias arising from errors in calculated doses. We summarize calculated doses and illustrate their change and elaboration through the various systems for a hypothetical example case in each city. We conclude with a description of current efforts and plans for further improvements.

Body Burden↗

PubMed2005

Histologic characteristics of skin cancer in Hiroshima and Nagasaki: background incidence and radiation effects.

Skin cancers, though rare in Japan, have reportedly been on the rise, but little else is known about epidemiologic features of different histologic types of skin cancer. The Life Span Study cohort, which consists of 93,700 atomic-bomb survivors, many of whom were exposed to negligibly low radiation doses, and 26,600 people not exposed to radiation, enables a population-based study of spontaneous as well as radiation-related cancer risk. Skin tumor incident cases diagnosed between 1958 and 1987 were ascertained by linkage to the Hiroshima and Nagasaki tumor registries augmented by searches of other data sources. Study pathologists reviewed tumor specimens and pathology reports and classified tumors using the World Health Organization classification scheme. They identified 274 primary incident skin cancers, of which 106 were basal cell carcinoma (BCC), 81 were squamous cell carcinoma (SCC), and 14 were malignant melanomas. Background incidence rates and radiation effects were assessed by Poisson regression models allowing for the effects of demographic and other covariates. BCC and SCC background incidence rates were both about 3 per 100,000 per year. BCCs were mainly on the head/neck (81%), whereas SCCs occurred most frequently on the arms/legs (45%) and head/neck (29%), consistent with the presumed role played by solar UV exposure in skin cancer. The BCC rates increased significantly between 1958 and 1987, whereas the SCC rates remained unchanged. The excess absolute risk of BCC per unit skin surface area related to atomic-bomb radiation exposure did not differ between UV-exposed and shielded parts of the body, suggesting the additivity of the radiation-related and background BCC risks.

Adolescent↗

PubMed2005

Male breast cancer incidence among atomic bomb survivors.

To learn more about the role of ionizing radiation in the development of male breast cancer, we evaluated male breast cancer incidence among 45 880 male members of the Life Span Study cohort of Japanese atomic bomb survivors. Male breast cancers, diagnosed between January 1, 1958, and December 31, 1998, were identified through the Hiroshima and Nagasaki Tumor Registries. Nine male breast cancers were diagnosed among exposed Life Span Study members (crude rate = 1.8 per 100,000 person-years), and three were diagnosed among nonexposed cohort members (crude rate = 0.5 per 100,000 person-years). A statistically significant dose-response relation was observed (excess relative risk per sievert = 8, 95% confidence interval = 0.8 to 48; P = .01). Our finding of a statistically significant association between ionizing radiation and male breast cancer incidence adds to the very limited information that shows an association between radiation exposure and an increased risk of male breast cancer.

Aged↗

PubMed2004

Clinical and epidemiologic characteristics of first primary tumors of the central nervous system and related organs among atomic bomb survivors in Hiroshima and Nagasaki, 1958-1995.

BACKGROUND: Analysis conducted in the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki found a significant dose-related excess of tumors of the central nervous system (CNS) and the pituitary gland. The objective of the current study was to evaluate clinical and epidemiologic characteristics of first primary tumors of the CNS and the pituitary gland in this cohort and to compare them with characteristics among other populations. METHODS: CNS and pituitary gland tumors that were diagnosed between 1958 and 1995 among 80,160 LSS cohort members were ascertained through Hiroshima and Nagasaki tumor registries, autopsy reports, and other sources. Pathologists reviewed all available records and slides to verify histologic diagnoses. Poisson regression analysis was used to model background incidence rates allowing for radiation effects. RESULTS: Meningioma was the most common tumor among clinically diagnosed tumors, followed by neuroepithelial tumor, schwannoma, and pituitary tumor. The overall incidence of these tumors increased initially with age but declined among the elderly. For all age groups and for both genders, incidence increased over time. By contrast, when tumors diagnosed at autopsy were included, incidence rose continuously with age and was stable over time. CONCLUSIONS: The main characteristics of CNS and pituitary gland tumors diagnosed in the LSS cohort were consistent with the characteristics of "spontaneous" tumors observed in other population-based studies. The predominance of meningiomas over neuroepithelial tumors in the Japanese population was noteworthy and warrants further investigation. The secular rise in incidence of all clinically diagnosed CNS and pituitary gland tumors is most likely to be attributable to the increased use of new imaging techniques.

Adult↗

PubMed2004

Effect of recent changes in atomic bomb survivor dosimetry on cancer mortality risk estimates.

The Radiation Effects Research Foundation has recently implemented a new dosimetry system, DS02, to replace the previous system, DS86. This paper assesses the effect of the change on risk estimates for radiation-related solid cancer and leukemia mortality. The changes in dose estimates were smaller than many had anticipated, with the primary systematic change being an increase of about 10% in gamma-ray estimates for both cities. In particular, an anticipated large increase of the neutron component in Hiroshima for low-dose survivors did not materialize. However, DS02 improves on DS86 in many details, including the specifics of the radiation released by the bombs and the effects of shielding by structures and terrain. The data used here extend the last reported follow-up for solid cancers by 3 years, with a total of 10,085 deaths, and extends the follow-up for leukemia by 10 years, with a total of 296 deaths. For both solid cancer and leukemia, estimated age-time patterns and sex difference are virtually unchanged by the dosimetry revision. The estimates of solid-cancer radiation risk per sievert and the curvilinear dose response for leukemia are both decreased by about 8% by the dosimetry revision, due to the increase in the gamma-ray dose estimates. The apparent shape of the dose response is virtually unchanged by the dosimetry revision, but for solid cancers, the additional 3 years of follow-up has some effect. In particular, there is for the first time a statistically significant upward curvature for solid cancer on the restricted dose range 0-2 Sv. However, the low-dose slope of a linear-quadratic fit to that dose range should probably not be relied on for risk estimation, since that is substantially smaller than the linear slopes on ranges 0-1 Sv, 0-0.5 Sv, and 0- 0.25 Sv. Although it was anticipated that the new dosimetry system might reduce some apparent dose overestimates for Nagasaki factory workers, this did not materialize, and factory workers have significantly lower risk estimates. Whether or not one makes allowance for this, there is no statistically significant city difference in the estimated cancer risk.

Adolescent↗

PubMed2003

Cancer risks attributable to low doses of ionizing radiation: assessing what we really know.

High doses of ionizing radiation clearly produce deleterious consequences in humans, including, but not exclusively, cancer induction. At very low radiation doses the situation is much less clear, but the risks of low-dose radiation are of societal importance in relation to issues as varied as screening tests for cancer, the future of nuclear power, occupational radiation exposure, frequent-flyer risks, manned space exploration, and radiological terrorism. We review the difficulties involved in quantifying the risks of low-dose radiation and address two specific questions. First, what is the lowest dose of x- or gamma-radiation for which good evidence exists of increased cancer risks in humans? The epidemiological data suggest that it is approximately 10-50 mSv for an acute exposure and approximately 50-100 mSv for a protracted exposure. Second, what is the most appropriate way to extrapolate such cancer risk estimates to still lower doses? Given that it is supported by experimentally grounded, quantifiable, biophysical arguments, a linear extrapolation of cancer risks from intermediate to very low doses currently appears to be the most appropriate methodology. This linearity assumption is not necessarily the most conservative approach, and it is likely that it will result in an underestimate of some radiation-induced cancer risks and an overestimate of others.

Biophysical Phenomena↗

PubMed2003

Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950-1997.

This continues the series of general reports on mortality in the cohort of atomic bomb survivors followed up by the Radiation Effects Research Foundation. This cohort includes 86,572 people with individual dose estimates, 60% of whom have doses of at least 5 mSv. We consider mortality for solid cancer and for noncancer diseases with 7 additional years of follow-up. There have been 9,335 deaths from solid cancer and 31,881 deaths from noncancer diseases during the 47-year follow-up. Of these, 19% of the solid cancer and 15% of the noncancer deaths occurred during the latest 7 years. We estimate that about 440 (5%) of the solid cancer deaths and 250 (0.8%) of the noncancer deaths were associated with the radiation exposure. The excess solid cancer risks appear to be linear in dose even for doses in the 0 to 150-mSv range. While excess rates for radiation-related cancers increase throughout the study period, a new finding is that relative risks decline with increasing attained age, as well as being highest for those exposed as children as noted previously. A useful representative value is that for those exposed at age 30 the solid cancer risk is elevated by 47% per sievert at age 70. There is no significant city difference in either the relative or absolute excess solid cancer risk. Site-specific analyses highlight the difficulties, and need for caution, in distinguishing between site-specific relative risks. These analyses also provide insight into the difficulties in interpretation and generalization of LSS estimates of age-at-exposure effects. The evidence for radiation effects on noncancer mortality remains strong, with risks elevated by about 14% per sievert during the last 30 years of follow-up. Statistically significant increases are seen for heart disease, stroke, digestive diseases, and respiratory diseases. The noncancer data are consistent with some non-linearity in the dose response owing to the substantial uncertainties in the data. There is no direct evidence of radiation effects for doses less than about 0.5 Sv. While there are no statistically significant variations in noncancer relative risks with age, age at exposure, or sex, the estimated effects are comparable to those seen for cancer. Lifetime risk summaries are used to examine uncertainties of the LSS noncancer disease findings.

Adolescent↗

PubMed2003

Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1990.

An incidence survey of the Life Span Study (LSS) population found 1093 breast cancers among 1059 breast cancer cases diagnosed during 1950-1990. As in earlier breast cancer surveys of this population, a linear and statistically highly significant radiation dose response was found. In the analysis, particular attention was paid to modification of radiation dose response by age at exposure (e) and attained age (a). Dose-specific excess relative risk (ERR(1Sv)) decreased with increasing values of e and a. A linear dose-response model analysis, with e and a as exponential age modifiers, did not conclusively discriminate between the two variables as modifiers of dose response. A modified isotonic regression approach, requiring only that ERR(1Sv) be monotonic in age, provides a fresh perspective indicating that both e and a are important modifiers of dose response. Exposure before age 20 was associated with higher ERR(1Sv) compared to exposure at older ages, with no evidence of consistent variation by exposure age for ages under 20. ERR(1Sv) was observed to decline with increasing attained age, with by far the largest drop around age 35. Possible explanations for these observations are discussed, along with research approaches that might provide more information.

Adult↗

PubMed2002

Tumors of the nervous system and pituitary gland associated with atomic bomb radiation exposure.

BACKGROUND: The risk of developing nervous system tumors following exposure to ionizing radiation is not well quantified. We characterized the incidence of nervous system tumors among atomic bomb survivors as a function of radiation dose. METHODS: Tumors of the nervous system and pituitary gland diagnosed between 1958 and 1995 among 80 160 atomic bomb survivors were ascertained using the Hiroshima and Nagasaki tumor registries, medical records, and death certificates. Pathologists reviewed slides and medical records to provide histologic diagnoses. Poisson regression analyses were used to characterize radiation effects on tumor incidence, which are expressed as excess relative risk per sievert (ERR(Sv)). All statistical tests were two-sided. RESULTS: A statistically significant dose-related excess of nervous system tumors was observed in the cohort (ERR(Sv) = 1.2, 95% confidence interval [CI] = 0.6 to 2.1). The highest ERR(Sv) was seen for schwannoma (4.5, 95% CI = 1.9 to 9.2). The risk for all other nervous system tumors as a group is also statistically significantly elevated (ERR(Sv) = 0.6, 95% CI = 0.1 to 1.3). Risk increases, although not statistically significant, were seen for meningiomas (ERR(Sv) = 0.6, 95% CI = -0.01 to 1.8), gliomas (ERR(Sv) = 0.6, 95% CI = -0.2 to 2.0), other nervous system tumors (ERR(Sv) = 0.5, 95% CI = <-0.2 to 2.2), and pituitary tumors (ERR(Sv) = 1.0, 95% CI = <-0.2 to 3.5). The dose-response relationships were linear. For nervous system tumors other than schwannoma, excess risks were higher for men than for women and for those exposed during childhood than for those exposed during adulthood. CONCLUSIONS: A statistically significant dose response was observed for all nervous system tumors combined and for schwannoma considered separately, indicating that exposure to even moderate doses (i.e., <1 Sv) of radiation is associated with an elevated incidence of nervous system tumors.

Adult↗

PubMed2002

Radiation effects on breast cancer risk: a pooled analysis of eight cohorts.

Breast cancer incidence rates after radiation exposure in eight large cohorts are described and compared. The nature of the exposures varies appreciably, ranging from a single or a small number of high-dose-rate exposures (Japanese atomic bomb survivors, U.S. acute post-partum mastitis patients, Swedish benign breast disease patients, and U.S. infants with thymic enlargement) to highly fractionated high-dose-rate exposures (two U.S. tuberculosis cohorts) and protracted low-dose-rate exposure (two Swedish skin hemangioma cohorts). There were 1,502 breast cancers among 77,527 women (about 35,000 of whom were exposed) with 1.8 million woman-years of follow-up. The excess risk depends linearly on dose with a downturn at high doses. No simple unified summary model adequately describes the excess risks in all groups. Excess risks for the thymus, tuberculosis, and atomic bomb survivor cohorts have similar temporal patterns, depending on attained age for relative risk models and on both attained age and age at exposure for excess rate models. Excess rates were similar in these cohorts, whereas, related in part to the low breast cancer background rates for Japanese women, the excess relative risk per unit dose in the bomb survivors was four times that in the tuberculosis or thymus cohorts. Excess rates were higher for the mastitis and benign breast disease cohorts. The hemangioma cohorts showed lower excess risks suggesting ameliorating dose-rate effects for protracted low-dose-rate exposures. For comparable ages at exposure (approximately 0.5 years), the excess risk in the hemangioma cohorts was about one-seventh that in the thymus cohort, whose members received acute high-dose-rate exposures. The results support the linearity of the radiation dose response for breast cancer, highlight the importance of age and age at exposure on the risks, and suggest a similarity in risks for acute and fractionated high-dose-rate exposures with much smaller effects from low-dose-rate protracted exposures. There is also a suggestion that women with some benign breast conditions may be at elevated risk of radiation-associated breast cancer.

Adolescent↗