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Biomedical subjects

D G Hoel

Publications and source records attributed to D G Hoel.

At least 73 records · Page 4Linked to original sources
PubMed1983

'Hormonal' risk factors, 'breast tissue age' and the age-incidence of breast cancer.

For most cancer sites there is a linear log-log relationship between incidence and age. This relationship does not hold for breast cancer, and certain 'key' breast cancer risk factors suggest that breast tissue does not 'age' in step with calendar time. A quantitative description of 'breast tissue age' is suggested which brings the age-incidence curve of breast cancer into line with the common log-log cancers and explains quantitatively the known key risk factors. The model also explains the 'anomalous' finding that although early first birth is protective, late first birth carries a higher risk than nulliparity. US breast cancer rates are some four to six times the rates in Japan--the model suggests that the key risk factors, when considered jointly with weight, can explain about 85% of the difference.

Adolescent↗
PubMed1983

Implication of nonlinear kinetics on risk estimation in carcinogenesis.

Efforts in estimating carcinogenic risk in humans from long-term exposure to chemical carcinogens have centered on the problem of low-dose extrapolation. For chemicals with metabolites that interact with DNA, it may be more meaningful to relate tumor response to the concentration of the DNA adducts in the target organ rather than to the applied dose. Many data suggest that the relation between tumor response and concentration of DNA adducts in the target organ may be linear. This implies that the nonlinearities of the dose-response curve for tumor induction may be due to the kinetic processes involved in the formation of carcinogen metabolite--DNA adducts. Of particular importance is the possibility that the kinetic processes may show a nonlinear "hockey-stick" like behavior which results from saturation of detoxification or DNA repair processes. The mathematical models typically used for low-dose extrapolation are shown potentially to overestimate risk by several orders of magnitude when nonlinear kinetics are present.

Animals↗
PubMed1983

Secular trends in the distributions of the breast cancer risk factors--menarche, first birth, menopause, and weight--in Hiroshima and Nagasaki, Japan.

The results of a mail survey completed by approximately 21,000 female atomic bomb survivors in Hiroshima and Nagasaki in 1970 are studied with respect to menarche, first birth, menopause, and weight. These known risk factors for breast cancer can be used to explain some but not all of the differences in Japanese and US breast cancer rates. The results for age at menarche are the most striking, with the presence of a strong secular trend. The average age at menarche in Japan was observed to decrease from 16.4 years for women born in 1902 to 14.4 years for women born in 1942. However, a temporary increase was observed in women whose menarche was expected to occur during the war years of the early 1940s. Differences between US and Japanese women were also observed in age at first birth and nulliparity rates. Age at menopause was similar for the two groups, although US women have a considerably higher rate of surgically induced menopause. Within each birth cohort, it is shown that body weight is negatively correlated with age at menarche and positively correlated with age at menopause.

Adult↗
PubMed1981

Some practical problems arising from use of the gamma multihit model for risk estimation.

The Scientific Committee of the Food Safety Council recently recommended use of the gamma multihit model for risk assessment. Some practical problems arising from the use of this model are presented. In some instances the model produces what appear to be unreasonably high "safe dose" estimates. In other instances the estimates appear unrealistically low. Neither the original "standard" nor the "conservative" confidence limits seem adequate for practical application. The assumptions leading to the use of Abbott's correction are difficult to verify, but have a great effect on safe dose estimates. Indeed, the introduction of as little as 1% additive background into the gamma multihit model leads to safe dose estimates closer to those produced by the Armitage-Doll model than to those of the pure gamma multihit model.

Aflatoxin B1↗
PubMed1980

Incorporation of background in dose-response models.

Dose-response models are generally classified as either threshold-tolerance or mechanism models. These models are briefly reviewed and their impact upon low-dose estimation is discussed. The concept of independent versus additive backgrounds is explored. The mathematical implications are considered with the conclusion that additive background implies linearity and that the assumption of total independence of background is required to justify nonlinearity at low doses. This finding has important implications to low-dose extrapolations for the purpose of risk estimation.

Animals↗
PubMed1979

Statistical design of toxicity assays: role of genetic structure of test animal population.

This paper concerns certain statistical aspects of the problem of among-strain differences in cancer susceptibility and how these differences may affect the design of toxicity assays. First, the data of Innes et al. (1969) were examined to investigate the magnitude of within-study, between-strain differences in tumor induction. Although there was a very high overall association between mouse strains with respect to the induction of hepatomas, evidence of strain-to-strain variability was found for several compounds. Next, a number of long-term carcinogenicity studies with DDT were considered, and among-strain differences in cancer susceptibility for this compound were noted. Finally, it was shown that if susceptible subgroups do exist, and certain simplifying assumptions are made, then in many cases tumor increases can be detected more readily by studying several inbred mouse strains rather than a single outbred stock.

Animals↗
PubMed1979

Animal experimentation and its relevance to man.

The problem of quantitatively estimating human cancer risk based upon animal carcinogenesis studies is reviewed. Mathematical functions for dose-response relationships are discussed with particular emphasis on multistage models. These models are based upon a single cell somatic mutation theory for the carcinogenesis process. It is shown that the multistage model and others which incorporate background additively are well approximated in low dose region by a linear function. The relationship between time-to-tumor and the multistage model is indicated. This relationship is important when dealing with less than life time exposure such as with data from many occupational studies. Design of bioassay experiments and its impact on risk estimation is noted. Finally, the problem of species-to-species extrapolation is considered.

Carcinogens↗
PubMed1979

Statistical approaches to toxicological data.

Statistical techniques as applied to toxicological data are discussed. Issues concerning statistical hypothesis testing and combining studies are considered as well as design of experiments. The problems surrounding risk assessment are also mentioned.

Animals↗
PubMed1976

Fundamental carcinogenic processes and their implications for low dose risk assessment.

Various possible models of carcinogenesis are analyzed with respect to low dose kinetics. The importance of background carcinogenesis upon the shape of the dose-response curve at low dose is emphasized. It is shown that, if carcinogenesis by an external agent acts additively with any already ongoing process, then under almost any model the response will be linear at low dose. Measures of the degree of linearity are obtained for multistage models of carcinogenesis, where it is shown that throughout the dose range where the extra risk is less than the spontaneous risk linear extrapolation must be quite accurate.

Carcinogens, Environmental↗