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R Doll

Publications and source records attributed to R Doll.

At least 37 records · Page 2Linked to original sources
PubMed2001

Diet, smoking and lung cancer: a case-control study of 1000 cases and 1500 controls in South-West England.

We have examined the relationship between diet and lung cancer in a case-control study of 982 cases of lung cancer and 1486 population controls in south-west England in which subjects were interviewed personally about their smoking habits and their consumption of foods and supplements rich in retinol or carotene. Analyses were performed for 15 dietary variables, including intake of pre-formed retinol and carotene. There were significant associations (P< 0.01) with lung cancer risk for 13 of the variables, eight of which remained after adjustment for smoking. When the 15 variables were considered simultaneously, independent significant associations remained for 5: pre-formed retinol (increased risk), and fish liver oil, vitamin pills, carrots and tomato sauce (decreased risk). It is unlikely that all five associations represent biological effects, or that they can all be explained by residual confounding by smoking, or by biases. We conclude that there is at least one as yet unidentified factor that is causally related to lung cancer risk and of considerable importance in terms of attributable risk in this population.

Carotenoids↗
PubMed2001

Cohort studies: history of the method. I. Prospective cohort studies.

The term "cohort study" was introduced by Frost in 1935 to describe a study that compared the disease experience of people born at different periods, in particular the sex and age specific incidence of tuberculosis and the method was extended to the study of non-communicable disease by Korteweg who used it 20 years later to analyse the epidemic of lung cancer in the Netherlands. Such studies are now best described as generation studies or generation cohort studies to distinguish them from the common type of study that is now carried out that consists in defining groups of individuals distinguished by some variable (such as place of residence, occupation, behaviour, or environmental exposure) and following them up to see if the incidence or mortality rates vary with the selected variable. This type of study is now one of the most important tools for epidemiological investigation. Initially called prospective studies, because the information characterising the individuals in the cohorts was recorded before the onset of disease, they are now preferably called cohort studies and distinguished as prospective cohort studies, If the information obtained relates to the subjects at the time the study is started and they are then followed, or retrospective cohort studies, if the information characterising the individuals was recorded sometime in the past (for example, the receipt of radiotherapy, or entry to a specific occupation). Studies of either type have the great advantage that they avoid all the most important sources of bias that may affect case-control-studies, but the disadvantage that because incidence rates and more specifically mortality rates are commonly low, large numbers of subjects have to be followed for several (if not many) years to obtain statistically significant results. Several early prospective studies are described: Namely, those of 34,000 male British doctors, 190,000 male and female American citizens with different smoking habits, some 5,000 middle aged residents of Framingham with different blood pressures, blood cholesterol levels, etc, and 13,000 children born in the UK in one week in 1946 with different family backgrounds.

Cohort Studies↗
PubMed2001

Radon: a likely carcinogen at all exposures.

BACKGROUND: Radon is a well-established lung carcinogen that has been extensively studied. Very high concentrations can occur in some underground mines. Concentrations also tend to build up in homes. MATERIALS AND METHODS: Epidemiological studies of radon-exposed miners and of residential radon and lung cancer are reviewed. Quantitative estimates of the risk of lung cancer, based on the experience of the miners, are applied to residential radon exposures in the United Kingdom. Strategies for the prevention of lung cancer induced by residential radon are discussed. RESULTS: Estimates are uncertain, but residential radon is probably responsible for about 2000 lung cancer deaths per year in the United Kingdom, or around 6% of the total, making it the second biggest cause after smoking. Over 80% of the deaths are estimated to occur at ages less than 75 and over 80% in smokers or ex-smokers. Around 90% of radoninduced deaths in the United Kingdom probably occur as a result of exposures to radon concentrations below the currently recommended action level of 200 Bq m(-3). CONCLUSIONS: Further work is needed to obtain more reliable estimates of the risk of lung cancer associated with residential radon and on the cost-effectiveness of various intervention strategies before the most appropriate policies can be developed for managing exposure to this natural carcinogen.

Air Pollution, Indoor↗
PubMed2001

100 years of observation on British radiologists: mortality from cancer and other causes 1897-1997.

Radiologists and radiotherapists were one of the earliest occupational groups to be exposed to ionizing radiation. Their patterns of mortality provide information on the long-term effects of fractionated external radiation exposure. British radiologists who registered with a radiological society between 1897 and 1979 have now been followed-up until 1 January 1997, and the mortality experience examined among those who registered with a society after 1920, when the first radiological protection recommendations were published. The observed number of cancer deaths in those who registered after 1920 was similar to that expected from death rates for all medical practitioners combined (SMR=1.04; 95% CI 0.89-1.21). However, there was evidence of an increasing trend in risk of cancer mortality with time since first registration with a radiological society (p=0.002), such that in those registered for more than 40 years there was a 41% excess risk of cancer mortality (SMR=1.41; 95% CI 1.03-1.90). This is probably a long-term effect of radiation exposure in those who first registered during 1921-1935 and 1936-1954. There was no evidence of an increase in cancer mortality among radiologists who first registered after 1954, in whom radiation exposures are likely to have been lower. Non-cancer causes of death were also examined in more detail than has been reported previously. There was no evidence of an effect of radiation on diseases other than cancer even in the earliest radiologists, despite the fact that doses of the size received by them have been associated with more than a doubling in the death rate among the survivors of the Japanese atomic bombings.

Cause of Death↗
PubMed2000

Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies.

OBJECTIVE AND DESIGN: To relate UK national trends since 1950 in smoking, in smoking cessation, and in lung cancer to the contrasting results from two large case-control studies centred around 1950 and 1990. SETTING: United Kingdom. PARTICIPANTS: Hospital patients under 75 years of age with and without lung cancer in 1950 and 1990, plus, in 1990, a matched sample of the local population: 1465 case-control pairs in the 1950 study, and 982 cases plus 3185 controls in the 1990 study. MAIN OUTCOME MEASURES: Smoking prevalence and lung cancer. RESULTS: For men in early middle age in the United Kingdom the prevalence of smoking halved between 1950 and 1990 but the death rate from lung cancer at ages 35-54 fell even more rapidly, indicating some reduction in the risk among continuing smokers. In contrast, women and older men who were still current smokers in 1990 were more likely than those in 1950 to have been persistent cigarette smokers throughout adult life and so had higher lung cancer rates than current smokers in 1950. The cumulative risk of death from lung cancer by age 75 (in the absence of other causes of death) rose from 6% at 1950 rates to 16% at 1990 rates in male cigarette smokers, and from 1% to 10% in female cigarette smokers. Among both men and women in 1990, however, the former smokers had only a fraction of the lung cancer rate of continuing smokers, and this fraction fell steeply with time since stopping. By 1990 cessation had almost halved the number of lung cancers that would have been expected if the former smokers had continued. For men who stopped at ages 60, 50, 40, and 30 the cumulative risks of lung cancer by age 75 were 10%, 6%, 3%, and 2%. CONCLUSIONS: People who stop smoking, even well into middle age, avoid most of their subsequent risk of lung cancer, and stopping before middle age avoids more than 90% of the risk attributable to tobacco. Mortality in the near future and throughout the first half of the 21st century could be substantially reduced by current smokers giving up the habit. In contrast, the extent to which young people henceforth become persistent smokers will affect mortality rates chiefly in the middle or second half of the 21st century.

Adult↗
PubMed2000

Smoking and dementia in male British doctors: prospective study.

OBJECTIVE: To assess the possible association between smoking and dementia. DESIGN: Prospective study. SETTING: Cohort of British male doctors followed up since 1951. SUBJECTS: 34 439 male British doctors, with 24 133 deaths recorded. RESULTS: For all types of dementia combined the relative risk was 0.96 (95% confidence interval 0.78 to 1.18), based on 473 deaths at a mean age of 81 years. For probable or definite Alzheimer's disease, the relative risk in continuing smokers was 0.99 (0.78 to 1.25), based on 370 deaths at a mean age of 82 years. In aggregate, however, the other prospective studies indicate a direct, although not clearly significant, association between smoking and the onset of dementia in general and of Alzheimer's disease in particular. CONCLUSIONS: Contrary to previous suggestions persistent smoking does not substantially reduce the age specific onset rate of Alzheimer's disease or of dementia in general. If anything, it might increase rather than decrease the rate, but any net effect on severe dementia cannot be large in either direction.

Aged↗
PubMed2000

In vitro priming with adenovirus/gp100 antigen-transduced dendritic cells reveals the epitope specificity of HLA-A*0201-restricted CD8+ T cells in patients with melanoma.

Replication-deficient recombinant adenovirus (Ad) encoding human gp100 or MART-1 melanoma Ag was used to transduce human dendritic cells (DC) ex vivo as a model system for cancer vaccine therapy. A second generation E1/E4 region deleted Ad which harbors the CMV immediate-early promoter/enhancer and a unique E4-ORF6/pIX chimeric gene was employed as the backbone vector. We demonstrate that human monocyte-derived DC are permissive to Ad infection at multiplicity of infection between 100 and 500 and occurs independent of the coxsackie Ad receptor. Fluorescent-labeled Ad was used to assess the kinetics and distribution of viral vector within DC. Ad-transduced DC show peak transgene expression at 24-48 h and expression remains detectable for at least 7 days. DC transduced with replication-deficient Ad do not exhibit any unusual phenotypic characteristics or cytopathic effects. DC transduced with Ad2/gp100v2 can elicit tumor-specific CTL in vitro from patients bearing gp100+ metastatic melanoma. Using a panel of gp100-derived synthetic peptides, we show that Ad2/gp100v2-transduced DC elicit Ag-specific CTL that recognize only the G209 and G280 epitopes, both of which display relatively short half-lives ( approximately 7-8 h) on the surface of HLA-A*0201+ cells. Thus, patients with metastatic melanoma are not tolerant to gp100 Ag based on the detection of CD8+ T cells specific for multiple HLA-A*0201-restricted, gp100-derived epitopes.

Adenoviruses, Human↗
PubMed1999

Complementary therapy and cancer: decision making by patients and their physicians setting a research agenda.

An invitational meeting, entitled Complementary and Alternative Therapy: Decision Making by Cancer Patients and Their Physicians, brought together Canadian health care providers and researchers who had expertise in patient-physician communication with those who were knowledgeable about complementary therapy and cancer. The aim was to build on the existing knowledge base in both fields in order to determine the unanswered questions, the most important questions, and what methods can be applied for answering these questions. The interdisciplinary group employed a step-wise collaborative process to develop a suggested research agenda regarding decision making by physicians and their cancer patients regarding complementary therapy. The four themes identified are establishment of a registry for complementary therapy usage for cancer care; communication; outcomes measurement; and models of integration. It is hoped that these themes will be considered worthy of support by funding agencies and worthy of investigation by researchers.

Canada↗