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Biomedical subjects

J M Kaldor

Publications and source records attributed to J M Kaldor.

At least 19 recordsLinked to original sources
PubMed1992

Lung cancer following Hodgkin's disease: a case-control study.

It is recognized that survivors of Hodgkin's disease are at a substantially increased risk of lung cancer. A collaborative group of population-based cancer registries and major treatment centers carried out a case-control study, in which 98 cases of lung cancer were identified in patients who had survived at least 1 year following a diagnosis of Hodgkin's disease. A total of 259 matched controls were selected from patients with Hodgkin's disease who did not develop subsequent lung cancer, and for both cases and controls detailed information was abstracted from medical records concerning stage and treatment of Hodgkin's disease. Patients treated with chemotherapy alone had about twice the risk of developing lung cancer than those treated by radiotherapy alone or both modalities. There was no increase in risk with cumulative number of cycles of chemotherapy. Among patients treated with radiotherapy alone, there was an increase in risk related to estimated radiation dose to the lung. There was also a strong association between cigarette smoking and the risk of lung cancer. The finding of a higher risk following chemotherapy than following radiotherapy was unexpected, but could not be explained by any identified methodological flaws. A plausible inference from the study is that all forms of Hodgkin's disease therapy are carcinogenic to the lung and that, in particular, chemotherapy is associated with an increase in risk which is at least comparable to and perhaps higher than the risk produced by radiotherapy.

Antineoplastic Agents↗
PubMed1992

Prevalence of hepatitis C virus antibodies in Sydney blood donors.

OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) antibodies in the Sydney blood donor population. DESIGN: All blood donations collected from Red Cross blood donors in Sydney from February 1990 until April 1991 were tested for HCV antibodies. For those samples found reactive in an anti-HCV screening test, a confirmatory test was carried out for the presence of HCV antibodies and the alanine aminotransferase level was measured. RESULTS: The prevalence of repeated reactivity to the screening test was 0.45% among blood donations overall, and 1.02% in donors giving blood for the first time in the study period. The confirmatory test result was positive for 30.8% of donations found to be repeatedly reactive in the screening test. There was little change over the study period in the HCV antibody prevalence of donors giving blood for the first time, but there was a clear decrease in the prevalence among all donations. Prevalence in males was nearly twice the prevalence in females--a difference which was consistent across age groups. The highest prevalence in both sexes was in the age group 30-34 years. Among samples for which the screening test results was positive, there was a strong correlation between the reactivity recorded for the screening test and both the proportion found positive by the confirmatory test and the proportion with an elevated alanine aminotransferase level. CONCLUSION: The small proportion of blood donations found to be repeatedly reactive by anti-HCV screening and the relatively good correlation with the confirmatory test and liver function assay indicate that a policy of discarding these donations will decrease the risk of transfusion-transmitted HCV infection without materially affecting the supply of blood.

Adult↗
PubMed1992

Risk factors for hepatitis C virus infection in blood donors: a case-control study.

OBJECTIVE: To investigate risk factors for hepatitis C virus (HCV) infection in Sydney blood donors. DESIGN: Blood donors confirmed to be positive for HCV antibodies were compared with blood donors with a positive result of a screening assay, but whose HCV antibody status had not been confirmed. A questionnaire on sexual, parenteral and other potential risk factors was administered to both groups. SETTING: Blood Transfusion Service in Sydney. PARTICIPANTS: The study enrolled 220 donors who had confirmed HCV infection, and 210 donors who did not. RESULTS: The relative risk associated with injecting drug use was 63 (95% confidence interval, 19-260) when comparison was made with all other donors. Among donors who did not report injecting drug use, a significant, independent increase in risk was found in association with having had a tattoo. Among donors who did not give a history of parenteral exposure, there was a significantly greater risk in people with more than one life-time sexual partner than in those with at most one partner. CONCLUSION: A history of injecting drug use was elicited as the most important risk factor in Sydney blood donors with antibodies to hepatitis C. Having had a tattoo, and an increased number of lifetime sexual partners were also independently associated with HCV infection.

Adult↗
PubMed1992

Quantitative assessment of human cancer risk.

Because exposure to carcinogens cannot be eliminated, it has become important to define exposure levels which are acceptable to society or are irreducible. Quantitative assessment of cancer risk is part of this process. This paper presents a definition of risk and discusses the role of epidemiologic observation in the quantitative assessment of cancer risk, the estimation of risk from epidemiologic data, and the role of animal cancer bioassays in the quantitative assessment of cancer risk. It is emphasized that quantitative risk assessment is inevitably based on multiple assumptions. Where possible, the magnitude of errors associated with these assumptions should be stated, even to the extent of an acknowledgment of complete ignorance.

Animals↗
PubMed1990

Voluntary HIV antibody testing among STD clinic patients: a pilot study.

A pilot study was conducted with the aim of measuring the acceptability of voluntary testing for human immunodeficiency virus (HIV) antibody among patients attending sexually transmissible disease (STD) clinics. Three STD clinics, two public and one private, participated in the study which was conducted over a three-month period beginning in November 1988. For each patient attending the clinics, sex, date of birth, HIV transmission category and previous HIV test result were recorded. Patients who did not request the HIV antibody test were offered testing. Of the 2356 patients who were included in the analyses, 784 (34%) requested testing. For almost all patients (97%) who requested testing, a serum sample was collected and testing completed. Approximately half (55%) of those patients who were offered the test accepted testing. Overall, 70% of patients completed HIV antibody testing. Of the major transmission categories, the acceptance rate for those offered the test was lowest among homosexual men (45%), who also had the highest rate of HIV antibody seropositivity (11%) among those tested. Of patients who reported themselves to be HIV antibody seronegative prior to the pilot study, 78% were retested during the study and seven had a positive test for HIV antibody. We conclude that voluntary HIV antibody testing is acceptable in both public and private STD clinic settings, although a substantial amount of additional resources would need to be allocated to counselling if voluntary testing is to be introduced on a routine basis.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Leukemia following chemotherapy for ovarian cancer.

An international collaborative group of cancer registries and hospitals identified 114 cases of leukemia following ovarian cancer. We investigated the possible etiologic role of chemotherapy, radiotherapy, and other factors, using a case-control study design, with three controls matched to each case of leukemia. Chemotherapy alone was associated with a relative risk of 12 (95 percent confidence interval, 4.4 to 32), as compared with surgery alone, and patients treated with both chemotherapy and radiotherapy had a relative risk of 10 (95 percent confidence interval, 3.4 to 28). Radiotherapy alone did not produce a significant increase in risk as compared with surgery alone. The risk of leukemia was greatest four or five years after chemotherapy began, and the risk was elevated for at least eight years after the cessation of chemotherapy. The drugs cyclophosphamide, chlorambucil, melphalan, thiotepa, and treosulfan were independently associated with significantly increased risks of leukemia, as was the combination of doxorubicin hydrochloride and cisplatin. Chlorambucil and melphalan were the most leukemogenic drugs, followed by thiotepa; cyclophosphamide and treosulfan were the weakest leukemogens, and the effect per gram was substantially lower at high doses than at lower doses. The extent to which the relative risks of leukemia are offset by differences in chemotherapeutic effectiveness is not known.

Antineoplastic Agents↗
PubMed1990

Leukemia following Hodgkin's disease.

To investigate the effect of different treatments for Hodgkin's disease on the risk of leukemia, we used an international collaborative group of cancer registries and hospitals to perform a case-control study of 163 cases of leukemia following treatment for Hodgkin's disease. For each case patient with leukemia, three matched controls were chosen who had been treated for Hodgkin's disease but in whom leukemia did not develop. The use of chemotherapy alone to treat Hodgkin's disease was associated with a relative risk of leukemia of 9.0 (95 percent confidence interval, 4.1 to 20) as compared with the use of radiotherapy alone. Patients treated with both had a relative risk of 7.7 (95 percent confidence interval, 3.9 to 15). After treatment with more than six cycles of combinations including procarbazine and mechlorethamine, the risk of leukemia was 14-fold higher than after radiotherapy alone. The use of radiotherapy in combination with chemotherapy did not increase the risk of leukemia above that produced by the use of chemotherapy alone, but there was a dose-related increase in the risk of leukemia in patients who received radiotherapy alone. The peak in the risk of leukemia came about five years after chemotherapy began, and a large excess persisted for at least eight years after it ended. After adjusting for drug regimen, we found that patients who had undergone splenectomy had at least double the risk of leukemia of patients who had not, and an advanced stage of Hodgkin's disease carried a somewhat higher risk of leukemia than Stage I disease. We conclude that chemotherapy for Hodgkin's disease greatly increases the risk of leukemia and that this increased risk appears to be dose-related and unaffected by concomitant radiotherapy. In addition, the risk is greater for patients with more advanced stages of Hodgkin's disease and for those who undergo splenectomy.

Antineoplastic Agents↗
PubMed1990

Interaction between human carcinogens.

In the absence of direct information on the carcinogenicity of a complex mixture, assessment of its risk requires not only knowledge of the risks due to the separate components, but also assumptions about the interaction between the components. A formal definition of interaction is given, followed by a discussion of the theoretical basis for different kinds of interactions. Epidemiological studies which have considered the simultaneous effect of two chemical carcinogens are reviewed, and shown to provide examples of additivity, multiplicativity and interaction both intermediate between the two and greater than multiplicative. Finally, implications for the risk assessment of mixtures are discussed.

Carcinogens, Environmental↗
PubMed1990

Multistage theory of carcinogenesis: the epidemiological evidence for liver cancer.

Experimentalists have developed 2 stage carcinogenesis models within which initiation and promotion can be phenomenologically defined. For humans, no comparable sequential exposure situations have been studied, and the concepts of initiation and promotion cannot be defined in the same way that they have been for animal experiments. Nevertheless, there are epidemiological studies of human cancer which provide information on the effect of age at exposure, cessation of exposure and level of exposure on cancer risk which can be used to classify carcinogens according to their apparent mode of action. For the recognized human liver carcinogens, the available epidemiological data are not yet sufficiently detailed to permit clear conclusions about their role in multistage carcinogenesis.

Aflatoxins↗
PubMed1989

A case-control study of diet and breast cancer in Argentina.

A case-control study of breast cancer was carried out in La Plata, Argentina, where the incidence of the disease is comparable to the highest rates recorded worldwide. One hundred and fifty incident cases were identified through major hospitals. For each case, a hospital control, matched by age and hospital, and a neighbourhood control, matched by residential area and age, were also chosen. Cases and controls were interviewed to obtain information on past diet, as well as demographic and socio-economic characteristics, reproductive and menstrual history and other potential breast-cancer risk factors. The dietary information was obtained from questions on the consumption of specific food items and information on portion sizes from an earlier study was used to estimate intake of calories and selected nutrients. There was a substantial excess energy intake among cases as compared to both control groups, which was present across all 3 major macronutrients which contribute to total calories. Among the food groups, the consumption of eggs was a risk factor for breast cancer, and whole-milk products and green leafy vegetables were protective. After adjusting for the calorie difference in multivariate statistical analyses of nutrients, fibre and beta-carotene consumption were weakly protective. The results are discussed with reference to possible methodological difficulties and previous studies of diet and breast cancer.

Argentina↗
PubMed1989

Estimation of temporal effects in treatment-induced second cancer.

Cancer chemotherapy has been remarkably successful in the treatment of several types of malignancies, but has also been demonstrated to cause leukaemia and perhaps other cancer in long-term survivors. Radiotherapy also carries a carcinogenic risk. A large case-control study of second cancer has been carried out, with the aim of quantifying the risk due to chemotherapy and radiotherapy. One of the most important goals of this study is the estimation of the temporal pattern of risk following chemotherapy. Methods are presented for modelling risk as a function of type of treatment and the interval since treatment. The methods are applications of generally available linear regression programs for epidemiological data, and could be equally well applied to studies of occupationally induced cancer.

Age Factors↗
PubMed1989

Aplastic anemia, leukemia and other cancer mortality in a cohort of shoe workers exposed to benzene.

Benzene is a well documented carcinogen for the hematic and lymphopoietic system, and experimental research confirms its carcinogenicity for tumors of other sites. This report presents the results of a historical cohort study in a shoe manufacturing plant in Florence where cases of aplastic anemia and leukemia were reported in the 1960s. A total of 1008 men and 1005 women were considered eligible members of the cohort. For total mortality, comparing the rates of the cohort with the national rates, the standardized mortality ratio (SMR) was 79 for the women and 95 for the men. For the men excesses of risk for aplastic anemia [SMR 1566; 95% confidence interval (95% CI) 547-3264] and leukemia (SMR 400, 95% CI 146-870) were observed. The increased risk occurred among workers first employed during the period in which benzene was used, but the expected number of cases in the subsequent period was too small to evaluate whether any reduction in risk had occurred. No increasing pattern with duration of employment was discernible.

Adhesives↗
PubMed1988

Quantifying the carcinogenicity of antineoplastic drugs.

It has been well established that many of the drugs used in cancer therapy are themselves potentially carcinogenic. It is therefore important to quantify the carcinogenic risk associated with specific agents, and to investigate ways of predicting their risk from animal and in vitro studies. In this paper, an index of carcinogenic potency is defined, and applied to published data on acute non-lymphocytic leukemia following therapy with cytotoxic drugs used as single agents. Carcinogenic potency estimates for rats and mice are also obtained for 15 antineoplastic drugs, and the potency correlation between humans and rodents is examined for the five agents for which there are data in common. The broader implications for quantitative cancer risk prediction are discussed.

Animals↗
PubMed1988

Does human papillomavirus cause cervical cancer? The state of the epidemiological evidence.

The human papillomavirus has emerged over the past decade as the leading candidate to be the sexually transmitted aetiological factor in cervical cancer. Although it appears that papillomavirus types 16 and 18 are associated with a higher risk of advanced cervical neoplasia, most of the evidence comes from studies which do not satisfy basic epidemiological requirements, and are therefore difficult to interpret. The most significant problems are the small sample size, potentially biased selection of study subjects, the difficulties in cytologically distinguishing precancerous lesions from papilloma infection of the cervix, the unknown specificity and sensitivity of the various hybridisation methods for determining papillomavirus infection status, and the statistical analyses and presentation of results. On the basis of the existing studies, one is forced to conclude that, while experimental data suggest an oncogenic potential for HPV, the epidemiological evidence implicating it as a cause of cervical neoplasia is still rather limited.

DNA, Viral↗
PubMed1987

Second malignancies following testicular cancer, ovarian cancer and Hodgkin's disease: an international collaborative study among cancer registries.

Eleven population-based cancer registries tabulated second cancers among 133,411 patients diagnosed with testicular cancer, ovarian cancer or Hodgkin's disease between 1945 and 1984. Overall, 3,157 second cancers were observed, as compared with 2,420 expected at least one year after the first cancer. Survivors of testicular and ovarian cancer experienced 30% and 20% more cancers respectively than the general population comparison group, and patients previously diagnosed with Hodgkin's disease had an 80% excess of cancer. No information was available either on treatment for the first cancer, or other risk factors. However, temporal patterns in the risk of specific second cancers were analysed, with particular reference to the possible role of therapy for the first cancer. Leukaemia of the acute or non-lymphatic type, which has been previously linked to alkylating agent therapy, occurred in excess following all 3 first cancers, as did non-Hodgkin's lymphoma (overall relative risks of 6.1 and 1.8 respectively, with considerably higher relative risks following Hodgkin's disease). Other cancers for which important and plausibly therapy-induced excesses occurred were lung cancer following Hodgkin's disease (relative risk 1.9), breast cancer following Hodgkin's disease (relative risk 1.4) and bladder cancer following ovarian cancer and Hodgkin's disease (relative risks 1.7 and 2.2 in women, respectively). Rarer sites at which striking excesses occurred were the salivary gland, thyroid, bone and connective tissue. There were smaller, but clear excesses for cancers of the rectum and colon following ovarian cancer and testicular cancer, skin cancer following Hodgkin's disease, and kidney cancer following ovarian cancer. Overdiagnosis, misclassification of metastases and confounding by other risk factors were all considered as explanations of observed excesses. Nonetheless, it appeared that there are clear excess risks for cancers other than acute leukaemia which must be ascribed to therapy for the first cancer, especially in view of the possible under-reporting in registry material. Case-control studies are under way to provide information on the role of specific aspects of therapy.

Breast Neoplasms↗