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M Blettner

Publications and source records attributed to M Blettner.

89 records · Page 5Linked to original sources
PubMed1990

Adjusting for misselection using subsampling in epidemiological studies.

In epidemiological research it is sometimes necessary to conduct a case-control study in a part of the population which is not exposed to certain risk factors. Such a study design may be useful to investigate the risk related to a weak carcinogen in presence of other strong risk factors. It may happen that some individuals are wrongly included in the study group due to misreporting of the true exposure status. This misselection may cause biased odds ratio estimates of the factors of interest. It is therefore recommended that an evaluation study to validate the selection procedure is undertaken. We propose a two-stage sample design, consisting of a case-control study and a validation study in a subsample. Misselection rates in cases and control for different exposure groups may be estimated in the subsample and used to correct the odds ratio estimation from the first stage. It is shown how the total sample size should be attributed to the case-control sample and to the second-stage sample in order to give an unbiased estimate with minimal variance. The allocation is shown to be dependent on a number of parameters which is illustrated numerically and graphically. Efficiency considerations are also addressed.

Case-Control Studies↗
PubMed1990

Occupational risk factors for brain tumors: results from a population-based case-control study in Germany.

In a population-based case-control study in the Rhein-Neckar-Odenwald area (containing 1.3 million inhabitants) of the Federal Republic of Germany (FRG), risk factors were assessed for brain tumor development in 226 cases with primary brain tumors (ICD-9 191, 192.1, 192.0) and 418 population controls, interviewed by a standardized questionnaire. The analysis of occupational risk factors and smoking is presented. No elevated risk was found for smoking. Similarly, no significant effects were found for most occupations. Five specific occupational groups were examined because of a priori determination that they were of interest. Some categories showed slightly elevated risks but in none was the elevation statistically significant. A significant increase in risk for brain tumor development was found associated with working in electrical occupations for women (relative risk [RR] = 5.2; 95 percent confidence interval [CI] 1.4-20.1) but not for men (RR = 0.9, 95 percent CI 0.3-2.3).

Agricultural Workers' Diseases↗
PubMed1990

Birth defects among children born to a population occupationally exposed to pesticides in Colombia.

A case-referent study of birth defects was nested in a prevalence survey of adverse reproductive outcomes carried out among 8867 floriculture workers in Bogotá, Colombia. A total of 535 children born to these workers and reported by their parents as malformed and 1070 children selected at random as referents were invited to a medical examination including consultation with a geneticist and a clinical teratologist and a review of the medical records. Seventy-six percent of both groups attended the examination. Of 403 children reported as malformed, a birth defect was confirmed for only 154 (38%). On the other hand, of the 817 children reported as normal, 735 (90%) were normal, but 68 had a birth defect and 14 had other conditions. A case-referent analysis was then carried out including 222 children with birth defects and 443 referents. An increased risk was found only for birthmarks, and specifically for hemangiomas, for children with parents exposed to pesticides in the floriculture industry.

Abnormalities, Drug-Induced↗
PubMed1989

Radiation dose and breast cancer risk in patients treated for cancer of the cervix.

The relationship between breast cancer and radiation treatment for cervical cancer was evaluated in an international study of 953 women who subsequently developed breast cancer and 1,806 matched controls. Radiation doses to the breast (average 0.31 Gy) and ovaries (average 32 Gy) were reconstructed for exposed subjects on the basis of their original radiotherapy records. Overall, 88% of the breast cancer cases and 89% of the controls received radiation treatment [relative risk (RR) = 0.88; 95% confidence interval (CI) = 0.7-1.2]. Among women with intact ovaries (561 cases, 1,037 controls), radiotherapy was linked to a significant 35% reduction in breast cancer risk, attributable in all likelihood to the cessation of ovarian function. Ovarian doses of 6 Gy were sufficient to reduce breast cancer risk but larger doses did not reduce risk further. This saturation-type response is probably due to the killing of a critical number of ovarian cells. Cervical cancer patients without ovaries (145 cases, 284 controls) were analyzed separately because such women are at especially low natural risk for breast cancer development. In theory, any effect of low-dose breast exposure, received incidentally during treatment for cervical cancer, should be more readily detectable. Among women without ovaries, there was a slight increase in breast cancer risk (RR = 1.07; 95% CI = 0.6-2.0), and a suggestion of a dose response with the RR being 1.0, 0.7, 1.5 and 3.1 for breast doses of 0, 0.01-0.24, 0.25-0.49 and 0.50+ Gy, respectively. However, this trend of increasing RR was not statistically significant. If low-dose radiation increases the risk of breast cancer among women over age 40 years, it appears that the risk is much lower than would be predicted from studies of younger women exposed to higher doses.

Adult↗
PubMed1989

Chromosome aberrations in peripheral lymphocytes and radiation dose to active bone marrow in patients treated for cancer of the cervix.

An international study of cervical cancer patients reported a doubling of the risk for leukemia following radiotherapy. To evaluate the extent of residual chromosome damage in circulating T-cell lymphocytes in this population, approximately 200 metaphases were examined from each of 96 irradiated and 26 nonirradiated cervical cancer patients treated more than 17 years ago (average 23 years). Radiation dose averaged over the total red bone marrow was estimated to be 8.1 Gy. The type and frequency of stable and unstable chromosome aberrations were quantified in 24,117 metaphases. Unstable aberrations did not differ significantly between irradiated and nonirradiated patients (P greater than 0.5). Stable aberrations (i.e., translocations, inversions, or chromosomes with deleted segments), however, were significantly higher among irradiated (2.8 per 100 cells) compared to nonirradiated (0.7 per 100 cells) women (P less than 10(4). The frequency of these stable aberrations was found to increase significantly with increasing dose to the bone marrow. These data indicate that a direct relationship between radiation dose and extent of damage to somatic cells persists in populations and can be detected many years after partial-body radiation exposure. The stable aberration rate in irradiated cervical cancer patients was 50 to 75% lower than those observed 25 years or more after radiation exposure in atomic bomb survivors and in ankylosing spondylitis patients treated with radiotherapy. The average marrow dose was only 1 Gy in the examined atomic bomb survivors and 3.5 Gy in the ankylosing spondylitis patients. It appears, then, that a very high dose delivered to the pelvic cavity in fractionated doses resulted in far fewer persistent stable aberrations than lower doses delivered either in acute whole-body exposure or in fractionated doses to the spinal column and sacroiliac joints. The higher radiation dose and the concentration of that dose in a smaller area of the body appear to be responsible for the lower rate of persistent aberrations observed in cervical cancer patients.

Bone Marrow↗
PubMed1988

Radiation dose and second cancer risk in patients treated for cancer of the cervix.

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

Female↗
PubMed1987

The Copenhagen case-control study of bladder cancer: role of smoking in invasive and non-invasive bladder tumours.

A population based study of 388 cases of bladder cancer including papillomas and 787 controls in Greater Copenhagen confirmed the role of smoking in the aetiology of bladder cancer. Significantly increased relative risks were found for persons who had smoked only cigarettes (RR = 2.9; both sexes combined) and for mixed smokers including cigarettes (RR = 3.6; both sexes combined). Multiple logistic regression analysis showed significant influences of the amount (pack years) of cigarettes smoked and a reduced risk among persons who had stopped smoking. No significant effects of smoking pipe or cigars/cigarillos were apparent, and the present study does not confirm previous suggestions of associations between the smoking of cigars/cigarillos and bladder cancer in Denmark. Only a slight increase in relative risk with the amount smoked was found. The influence of smoking on bladder cancer risk was similar for tumours in stages T1 and T2-4 at diagnosis and also for tumours of grades 1-2 and grades 3-4 at diagnosis.

Aged↗
PubMed1987

Radiation dose and leukemia risk in patients treated for cancer of the cervix.

To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.

Adult↗
PubMed1986

The effect of nass use and smoking on the risk of oral leukoplakia.

The results of a survey of a population with a high incidence of oral cancer are presented in this paper. A remarkably high proportion (41%) of the men surveyed used nass, which is a mixture of tobacco, lime, ash, and cotton oil. The prevalence of oral leukoplakia, lesions thought to be a precursor of oral cancer, was high in persons who used nass (12%) and who smoked cigarettes (15%), and highest among those men who both used nass and smoked (21%). It has been shown that nass use increases the frequency of micronucleated cells in the exfoliated sublingual cells. The clastogenic and genotoxic effect of nass revealed in the study could be attributed to the presence of tobacco-specific N-nitroso compounds. However, the results of chemical analysis, which has shown that nass contains relatively low levels of these compounds, suggest that the relatively strong genotoxic activity of nass could primarily be associated with other chemicals, possibly oxidized phenolics. Despite the uncertainty as to which of the chemicals contained in nass are involved in the etiology of oral cancer and what exactly are the mechanisms of nass-induced carcinogenesis, the results of this study suggest that in populations where nass is widely used, oral leukoplakia and, most probably, oral cancer are conditions that could be prevented by the elimination of nass use and cigarette smoking.

Aged↗
PubMed1986

Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for esophageal cancer in Northern China: endogenous formation of nitrosoproline and its inhibition by vitamin C.

A total of 238 samples of 24-h urine were collected from inhabitants of high-risk (Lin-xian) and low-risk (Fan-xian) areas for esophageal cancer in northern China, according to three protocols: (a) from undosed subjects; (b) from subjects who had ingested 100 mg L-proline three times a day 1 h after each meal; and (c) from subjects in Lin-xian who had ingested 100 mg ascorbic acid together with 100 mg L-proline three times a day 1 h after each meal. As an index of individual exposure to N-nitroso compounds or their precursors, ingested in food and/or formed endogenously, the levels of four urinary N-nitrosamino acids and nitrate were determined. The amounts of N-nitrosoproline, N-nitrosothiazolidine 4-carboxylic acid, N-nitrososarcosine, and nitrate excreted in the 24-h urine of undosed subjects in Lin-xian were significantly higher than those in Fan-xian, indicating a higher exposure of the inhabitants in the high-risk area to N-nitroso compounds and their precursors. Ingestion of L-proline resulted in a marked increase in urinary N-nitrosoproline levels in inhabitants from both areas, suggesting that endogenous nitrosation may occur to a larger extent when appropriate amine precursors are ingested in foods. Intake of moderate doses of ascorbic acid by high-risk subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in undosed subjects in the low-risk area. If N-nitroso compounds formed in vivo are among the causative factors for esophageal cancer in this area of northern China, ascorbic acid appears to be effective in lowering the body burden of these carcinogenic compounds, thus offering a rational basis for long-term intervention studies in this area.

Adult↗
PubMed1985

Survey of a population with a high incidence of oral and oesophageal cancer.

The results of a survey of a population with a high incidence of oral and oesophageal cancer are presented. The population under study appears to have several epidemiologic characteristics, some of which may be associated with a high incidence of oral and oesophageal cancer. A remarkably high proportion (41%) of the men surveyed were nass users and this habit, like the use of other types of tobacco mixtures, has been related to oral cancer. Oral leukoplakia and chronic oesophagitis (conditions thought to be precursors of oral and oesophageal cancer) have been diagnosed in 11% and 60%, respectively, of the persons examined. Analysis of the relationship between nass use, cigarette smoking, oral leukoplakia and oesophagitis revealed that the prevalence of oral leukoplakia is highest among cigarette smokers who use nass. It appears that nass use does not affect the frequency of occurrence of chronic oesophagitis. However, a slight elevation of the prevalence odds ratio was observed for current smokers and drinkers. Biochemical analysis of the blood of a random sample of the surveyed population revealed low levels of riboflavin, vitamin A and carotenoids--vitamins that most probably have a protective effect against the development of cancer. The mutagenicity test has shown that nass contains a chemical or chemicals that exert a genotoxic effect. Chemical analysis revealed the presence in nass of tobacco-specific N-nitroso compounds.

Aged↗
PubMed1985

An investigation of the adequacy of a randomization.

A randomization actually performed in an individual-based double-blind intervention trial in cancer epidemiology is investigated concerning the resulting imbalance of treatment assignment. Complete randomization, permuted block procedures, and adaptive urn models are simulated in order to assess how representative the achieved distribution is for the procedure used and how other procedures would have performed on the given study population. The achieved randomization is deemed to be satisfactory and the different procedures are discussed in light of different logistic requirements. It is argued that such investigations should be carried out when debating the implications of a given randomization.

Adult↗
PubMed1985

Chemoprevention of oral and esophageal cancer in Uzbekistan, Union of Soviet Socialist Republics.

The results of a survey of a population with a high risk of oral and esophageal cancer and the outline of a chemoprevention scheme for persons found to have a precancerous condition of the mouth and esophagus are presented. Of a total of 1,569 men examined, 11% had preleukoplakia and leukoplakia of the mouth, and 60% of the 1,344 men in whom esophagogastroscopy was performed had chronic esophagitis. The relative risk of oral leukoplakia was highest (11.5) among men who smoke and use nass quid. The relative risk was also elevated for persons who only use nass quid (5.6) or who only smoke cigarettes (7.8). Nass use had no effect on the risk of esophagitis. A slight elevation of risk (1.9) of esophagitis was observed for current smokers and drinkers. Of the men from whom blood was drawn for analysis, 4%, 66%, and 86% had low levels of retinol, carotene, and riboflavin, respectively. The high prevalence of oral and esophageal precancerous conditions and low blood levels of riboflavin, carotene, and vitamin A observed in the surveyed population, as well as the existing evidence on the possible protective effect of these nutrients in carcinogenesis, provide an opportunity and a justification for the chemopreventive trial, with the regression of observed precancerous lesions as the end point of the study.

Aged↗
PubMedDate not supplied

[Follow up of long-term survivors after childhood cancer in Germany].

BACKGROUND: In recent years, the long-term survival of childhood cancer patients has increased considerably. While this is desirable, more patients with late effects are to be expected and studies thereof become increasingly important. We will need to be able to stay in touch with as many former patients as possible in order to make a systematic and comprehensive long-term follow-up possible. PATIENTS: Childhood cancer patients under 15 years of age at diagnosis resident in Germany and registered at the German Childhood Cancer Registry (GCCR). METHODS: The GCCR has established a 3-phase procedure for follow-up. We developed principles for the long-term follow up of these patients. They are based on the many years of experience at the GCCR and were developed based on the long-standing collaboration between the therapy optimization studies (TOS) in the Society for Paediatric Oncology and Haematology (GPOH) and the GCCR. RESULTS: Currently 8 012 adult survivors diagnosed before 2000 are under observation at the GCCR and could be contacted for studies. About half of the children diagnosed in the 1980ies still in follow-up have been under observation more than 14 years. When asked to personally extend the originally parental consent to data storage at the GCCR and the TOS at about 16 years of age, about 85 % of the patients agree. CONCLUSIONS: Establishing an open-end, systematic long-term follow-up will provide a unique and broad basis for paediatric oncology in Germany to perform representative studies regarding long-term survival after childhood cancer in Germany in the long run.

Adolescent↗