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Biomedical subjects

C E Land

Publications and source records attributed to C E Land.

At least 37 records · Page 2Linked to original sources
PubMed1993

Proliferative and nonproliferative breast disease in atomic bomb survivors. Results of a histopathologic review of autopsy breast tissue.

BACKGROUND: The risk of female breast cancer in association with radiation dose is well established, on the basis of follow-up studies of the atomic bomb survivors and other exposed populations. This association is especially strong for women exposed before 20 years of age and appears to be much weaker among women exposed after 40 years of age. METHODS: Breast tissue samples from 88 high-dose and 225 low-dose autopsy cases from the Radiation Effects Research Foundation Life Span Study sample were examined in detail to determine whether nonproliferative and proliferative breast lesions are associated with radiation dose. RESULTS: Prevalence of proliferative disease in general and atypical hyperplasia in particular were positively associated with radiation dose. The associations were strongest for subjects who were between 40 and 49 years of age at the time of the bombing. CONCLUSIONS: It is hypothesized that the strongest association in women 40 to 49 years of age may be related to the age dependence of radiation-induced breast cancer, in that potential cancers induced in this age group by radiation exposure may receive too little hormonal promotion to progress to frank cancers.

Adolescent↗
PubMed1993

Epstein-Barr virus in gastric carcinoma.

Epstein-Barr virus (EBV) is known to be related to lymphoid tumors and some types of epithelial tumors, including lymphoepithelioma-like gastric carcinoma with marked lymphocytic stroma. In this study, prevalence of EBV involvement in gastric cancer, and characteristics of tumors with such involvement, were investigated by EBV-encoded RNA 1 in situ hybridization applied to paraffin sections, including the tumor and adjacent gastric tissue, from 999 gastric carcinomas observed in 970 consecutive cases from a large Japanese hospital. EBV involvement occurred in 6.9 percent of lesions, a significantly lower proportion than has been observed in a North American series. Involvement was significantly more frequent among males, in tumors in the upper part of the stomach, and in adenocarcinomas of the moderately differentiated tubular and poorly differentiated solid or medullary types. Almost all carcinomas with marked lymphoid stroma were EBV-positive. Positive lesions were characterized by the presence of uniform hybridized signals in almost all carcinoma cells and by their absence from adjacent non-neoplastic tissue.

Adult↗
PubMed1993

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.

Adenocarcinoma↗
PubMed1991

Serum ferritin and stomach cancer risk among a Japanese population.

Using stored serum samples collected during from 1970 to 1972 and/or 1977 to 1979 from a fixed population in Hiroshima and Nagasaki, Japan, serum ferritin, transferrin, and ceruloplasmin levels were determined immunologically for persons in whom stomach (233 cases) or lung cancer (84 cases) subsequently developed as well as for their controls. An elevated stomach cancer risk was associated with low antecedent serum ferritin levels, with more than a threefold excess among those in the lowest compared with the highest ferritin quintile. The risk did not vary with the time between blood collection and stomach cancer onset, remaining high among those with low ferritin levels 5 or more years before cancer diagnosis. Achlorhydria, diagnosed in a sample of the population about 10 years before the 1970-to-1972 blood collection and up to 25 years before cancer, was an independent marker of stomach cancer risk. In combination, low serum ferritin and achlorhydria were associated with a tenfold increase in the subsequent risk. No effect of transferrin or ceruloplasmin, independent of ferritin, was observed in the gastric cancer risk, and the risk of lung cancer was not related to these three serum proteins. These prospective findings indicate that biologic markers of an increased risk of stomach cancer can be detected long before cancer onset.

Achlorhydria↗
PubMed1988

Time and dose dependency of bone-sarcomas in patients injected with radium-224.

The time course and dose dependency of the incidence of bone-sarcomas among 900 German patients treated with high doses of radium-224 is analysed in terms of a proportional hazards model with a log-normal dependency of time to tumor and a linear-quadratic dose relation. The deduced dose dependency agrees well with a previous analysis in terms of a non-parametric proportional hazards model, and confirms the temporal distribution which has been used in the Radioepidemiological Tables of NIH. However, the linear-quadratic dose-response model gives a risk estimate for low doses which is somewhat less than half that obtained under the assumption of linearity.

Adult↗
PubMed1988

New understanding from epidemiology--the next 25 years.

The epidemiology of radiation carcinogenesis is likely to be dominated during the next 25 y by the gradual maturation of major studies of populations exposed to substantial levels of radiation dose. During this period, for example, most of the new information on cancer risk among survivors of the 1945 atomic bombings of Hiroshima and Nagasaki will pertain to persons exposed at ages under 30. From the A-bomb survivor data and from a number of medically and occupationally irradiated populations now under study, it will be possible to construct a fairly complete picture of the temporal distribution of excess cancer risk over the remaining life span following exposure, a major source of uncertainty and controversy in current risk estimates. Provided that the necessary efforts are made, it should be possible to greatly increase our understanding of which organs and tissues are vulnerable to radiation carcinogenesis, variation by age at exposure and sex, and (what is most difficult at the present time) the influence of other risk factors and possible modifying factors on the magnitude of risk associated with radiation exposure. For some sites it may be possible, as it is now for breast cancer, to rule out certain broad classes of simple dose-response models. While the data gathered during the next 25 y will be nearly the last from some very important series, their information content should be extremely high. Thus, there is every reason to improve the resources, e.g., by improving dosimetry, enlarging samples, tapping new sources of case ascertainment, and gathering information on factors other than radiation dose. Modeling in epidemiological investigations depends heavily on work in experimental radiobiology. Thus far, the exchange has been largely in one direction, since epidemiological study design is mostly a matter of extracting information from "experiments" that have already taken place. With more epidemiological information, it seems reasonable to hope that detailed hypotheses, with direct relevance to areas of epidemiological uncertainty, may be generated suitable for experimental investigation. It seems likely that findings from large studies of populations exposed to relatively low levels of radiation, for which the signal-to-noise ratio is low, and for which random error and subtle sources of bias may have more than usual influence on reported results, will continue to generate controversy.(ABSTRACT TRUNCATED AT 400 WORDS)

Accidents↗
PubMed1987

Temporal distributions of risk for radiation-induced cancers.

Observations of cancer risk in irradiated human populations over time after exposure suggest that there are at least two, and perhaps more, very different patterns of temporal distribution of risk for radiation-induced cancer. The first, exemplified by bone sarcoma following therapeutic injection of 224Ra and chronic granulocytic leukemia in Japanese A-bomb survivors, is an early, wave-like pulse consisting of an increase in risk followed by a gradual decline back to baseline levels. The second, exemplified by breast cancer following a brief exposure to external gamma ray or X ray, and by lung cancer and stomach cancer in A-bomb survivors, is an increase in relative risk over about 10 years to a value which appears to remain constant over time thereafter. The first pattern suggests that tumor growth kinetics may play a central role in the temporal distribution of risk following exposure, while the second seems more consistent with multi-event models for carcinogenesis, in which radiation or some other cause of early events must be followed by one or more later events whose frequencies depend mainly on attained age. There are, however, other data that appear to conform to neither of the two models just mentioned. Influences of other cancer causes, like tobacco smoking, are potentially serious confounding factors in studies of induction period.

Adult↗
PubMed1987

Cancer mortality and radioactive fallout in southwestern Utah.

Cancer mortality was compared between a three-county region in southwestern Utah and the remainder of Utah in an investigation of reported excess cancer risks associated with residence in southwestern Utah during the period of above-ground nuclear tests at the Nevada Test Site. Because most of the fallout in southwestern Utah was deposited during 1953-1957, comparisons were limited to persons born before 1958, and deaths from leukemia and bone cancer during 1955-1980 and from other cancers during 1964-1980. There was no excess risk of cancer mortality in southwestern Utah, for single or grouped sites, with the single exception of leukemia which showed statistically significant odds ratios of 1.45 based on 62 deaths at all ages, and 2.84 based on nine deaths at ages 0-14. The finding for childhood leukemia was based on different time periods and geographic comparisons from those of two earlier studies in which no such excess was found. Mortality from all cancer sites combined was significantly lower in southwestern Utah than in the remainder of the state, even after adjustment for the higher proportion of (lower risk) Mormons in southwestern Utah. The present results, including the positive association for leukemia, are inconsistent with the high excess risks reported by Johnson (JAMA 1984;251:230-6) based on an interview survey of cancer incidence among long-term Mormon residents of southwestern Utah.

Adolescent↗
PubMed1987

Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1980.

Ascertainment of breast cancer incidence among the cohort of the RERF Life Span Study extended sample identified 574 breast cancers among 564 cases diagnosed during 1950-1980 of which 412 cancers were reviewed microscopically. There were no dose-dependent differences with respect to diagnostic certainty or histological type. As in previous studies, the dose response appeared to be roughly linear and did not differ between the two cities. The most remarkable new finding was the emergence of a radiation-related excess among women under 10 years of age at exposure. The risk of radiogenic breast cancer appears to decrease with increasing age at exposure, whether expressed in relative or absolute terms. These results suggest that exposure of female breast tissue to ionizing radiation at any time during the first four decades of life, even during the premature stage, can cause breast cancer later in life, and that the length of time that tumor promoters such as endogenous hormones operate following exposure has an important influence on the development of radiation-induced breast cancer. An unresolved question is whether breast cancer risk is increased by radiation exposure at ages older than 40.

Age Factors↗
PubMed1985

Extrapolation from large-scale radiation exposures: cancer.

Even though much is known about cancer risk associated with exposure to ionizing radiation, societal demands for detailed risk assessment go far beyond our ability to satisfy them according to customary standards of scientific accuracy. Society's requirement, however, is for the best information available, however good it may be, and not necessarily for the definitive solution to the problem posed. Bayesian methods may be useful for presenting incomplete and varied data and informed scientific opinion in a form suitable for use in societal decision making, while at the same time providing a disciplinary framework for incorporating opinion into scientific recommendations. Inferences about individual cases and their relationship to risk of radiation carcinogenesis provide an especially severe test of the completeness of our understanding of the relationship between exposure and risk. This is particularly true with respect to the distribution of excess risk over time following exposure. Recent work suggests that a standard model often used for projection of risk forward in time, the constant relative excess model, may give a surprisingly accurate picture of time to tumor for a number of cancer sites.

Breast Neoplasms↗
PubMed1984

Histologic review of breast cancer cases in survivors of atomic bombs in Hiroshima and Nagasaki, Japan.

A panel of Japanese and American pathologists reviewed existing histologic material used to study breast cancer risk among the A-bomb survivors in Hiroshima and Nagasaki, a population in which incidence studies have found a strong relationship between breast cancer risk and radiation dose. The primary charge to the panel was to define a body of confirmed cases in the Life Span Study sample of the Radiation Effects Research Foundation that would require little or no review for inclusion in future studies of breast cancer incidence. Broad agreement on histologic type was reached for 298 of 300 confirmed cases. The distribution of histologic types was, overall, similar to that seen in other studies of breast cancer in Japanese women, and did not appear to depend on dose; thus radiation-induced breast cancer appeared to be no different histologically from other breast cancer. Also, no evidence was found of variation in histologic type by city, age at exposure, age at diagnosis, or calendar time.

Adolescent↗
PubMed1984

Childhood leukemia and fallout from the Nevada nuclear tests.

Cancer mortality data from the National Center for Health Statistics, covering the period 1950 through 1978, were used to test a reported association between childhood leukemia and exposure to radioactive fallout from nuclear weapons tests in Nevada between 1951 and 1958. No pattern of temporal and geographic variation in risk supportive of the reported association was found. Comparison of these results with those presented in support of an association of risk with fallout suggests that the purported association merely reflects an anomalously low leukemia rate in southern Utah during the period 1944 to 1949.

Adolescent↗
PubMed1981

Statistical limitations in relation to sample size.

The statistical difficulties of estimating cancer risks from low doses of a carcinogen are illustrated by examples from radiation carcinogenesis. Although more is known about dose-response relationships for ionizing radiation than for any other environmental carcinogen, estimates of cancer risk from low radiation doses have been extremely controversial; disagreements by factors of 100 or more are not uncommon. Direct estimation, based on data from populations exposed to low doses, is usually impracticable because of sample size requirements. Curve-fitting analyses, by which higher dose data determine lower dose risk estimates, require simple dose-response models if the estimates are to be statistically stable. The current level of knowledge about biological mechanisms of carcinogenesis dose not usually permit the confident assumption of a simple model, however; thus frequently the choice is between unstable risk estimates obtained using general models and statistically stable estimates whose stability depends on arbitrary model assumptions.

Adult↗