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Biomedical subjects

L Dreyer

Publications and source records attributed to L Dreyer.

At least 19 recordsLinked to original sources

PTEN mutations in uterine sarcomas.

OBJECTIVE: Uterinesarcomas comprise three main types: carcinosarcomas, leiomyosarcomas, and endometrial stromal sarcomas. Carcinosarcomas are highly aggressive neoplasms with a biphasic histology of carcinomatous and sarcomatous elements. It is now generally accepted that carcinosarcomas are biphasic tumors that have to be regarded as endometrial carcinomas where metaplasia occurs. Mutations of the PTEN tumor suppressor gene, located on 10q23, play a significant role in the pathogenesis of the endometrioid type of endometrial carcinoma. Loss of heterozygosity of chromosome 10q has been reported in uterine leiomyosarcoma. Since little is known about the molecular pathobiology, our goal was to investigate the potential role of the PTEN gene in the carcinogenesis of uterine sarcomas. METHODS: We examined 21 carcinosarcomas, 21 leiomyosarcomas, and 5 endometrial stromal sarcomas using exon-by-exon polymerase chain reaction-single-strand conformation polymorphism analysis. RESULTS: Overall 8.5% (4/47) of uterine sarcomas were found to harbor somatic PTEN mutations. Of these, approximately 17% (3/18) were carcinosarcomas with endometrioid-type carcinoma components and approximately 5% (1/21) were leiomyosarcomas. No mutations were detected in carcinosarcomas with nonendometrioid carcinoma components (0/3) and in endometrial stromal sarcomas (0/5). CONCLUSIONS: These data suggest that intragenic PTEN mutations are involved in the genesis of uterine carcinosarcomas with endometrioid-type carcinoma components but rarely contribute to the pathobiology of uterine leiomyosarcomas.

Exons↗

[Cancer and prevention].

INTRODUCTION: The aim of the study was to estimate the preventable potential of various types of cancer in Denmark on the basis of present knowledge. MATERIAL AND METHODS: The well-documented factors in lifestyle and environment causing cancer in Denmark were identified from the IARC Monograph series. The population attributable risk per cent (PAR%) and the annual number of preventable cancers were calculated for each aetiology and cancer type around the year 2000. RESULTS: A large proportion of the cancers occurring in the lungs, larynx, upper digestive tract, skin, lower urinary tract, and the uterine cervix is potentially avoidable, whereas only a small proportion of breast and colorectal cancers is preventable on the given knowledge. The main causative factors include active and passive smoking, alcohol intake, exposure to asbestos and other occupational carcinogens, solar and ionising radiation, obesity, human papillomavirus infection in the female genital tract, and infection with Helicobacter pylori. More than 5000 cancers in men and almost 3500 in women annually in Denmark could have been avoided by eliminating exposure to these known carcinogens. This is equivalent to 39% and 23% of all cancers occurring respectively in men and women, around the year 2000. Smoking habits account for more than half of these avoidable cases. DISCUSSION: The incidence of cancer could be greatly reduced through primary prevention, especially of tobacco smoking, which is the major single factor. A large proportion of the cancers occurring in the lungs, larynx, upper digestive tract, skin, lower urinary tract, and the uterine cervix are potentially avoidable. More research in the field of aetiological factors causing female breast cancer and colorectal cancer is much needed in order to be able to prevent these types of cancer.

Alcohol Drinking↗

Uterine sarcomas in South African black women: a clinicopathologic study with ethnic considerations.

BACKGROUND: There is considerable evidence for a higher incidence of uterine sarcomas in blacks when compared to whites. However, whether this higher incidence is related to differences in clinicopathologic presentation is not known. PATIENTS AND METHODS: We reviewed slides and clinical charts of 81 patients with a primary diagnosis of uterine sarcoma referred between 1991 and 1999 to Kalafong Academic and Pretoria Academic Hospital. After review, 49 cases remained for study. RESULTS: Uterine sarcomas were distributed between leiomyosarcoma (LMS) (39%), carcinosarcoma (CS) (49%) and endometrial stromal sarcoma (ESS) (12%). LMS and ESS tend to present at an earlier age when compared to CS (respectively p < 0.008 and 0.02). Of women with LMS more women are premenopausal when compared to CS (p < 0.009). Lower abdominal pain is more common in LMS (p < 0.009), whereas bleeding is more common in women suffering from CS (p < 0.01). Lymphovascular space involvement and cervical involvement are more common in CS when compared to LMS. In CS, the carcinoma component has most of the metastatic potential. CONCLUSION: Among black South African women different clinicopathologic features for uterine LMS, CS and ESS are observed. We also present genetic and/or hormonal factors possibly contributing to the pathophysiology of uterine sarcomas in blacks.

Age Factors↗

Colorectal carcinoma--a new threat to black patients? A retrospective analysis of colorectal carcinoma received by the Institute for Pathology, University of Pretoria.

OBJECTIVE: To compare black and white patients with colorectal carcinoma treated at Pretoria Academic and Kalafong hospitals, and to compare pathological trends of our study population with others reported in the literature. DESIGN: A retrospective study of all cases of resected colorectal carcinomas received by our department during the periods 1986-1987 (82 cases) and 1996-1997 (91 cases). To investigate variables of age, race and gender distribution in the two study populations. METHODS: Routinely stained histological sections of all relevant cases were examined. Findings regarding age, gender, population group, anatomical location of the tumour and presence of other pathological lesions were recorded. Changes in the referral population and number of surgical specimens received were also considered during statistical analysis of the study findings. RESULTS: There has been a significant increase in the number of black patients with colorectal carcinoma at our Institute. In addition, adenomatous polyps were found in 9 of our black patients (1996/97). This is significantly higher than expected from reports in the literature. This could be predictive of an increase in incidence of colorectal carcinomas in our black population. Black patients were also found to be considerably younger at age of presentation than their white counterparts. A further significant finding was a considerable increase in the number of black females under the age of 40 years from 1986/87 to 1996/97. On the other hand, the number of white females above 40 years of age decreased considerably over this time. The reason for this finding is uncertain and warrants further study.

Adult↗

Immunohistochemical evaluation of Fhit protein expression in oral squamous cell carcinomas.

The expression of Fhit (fragile histidine triad) protein in oral squamous cell carcinoma (OSCC) and adjacent oral epithelium was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded blocks of 32 cases of OSCC. Rabbit polyclonal anti-GST-Fhit antiserum at 1:600 was used, after antigen enhancement in a microwave pressure cooker, in a saturated lead thiocyanate solution. This antiserum has been shown specifically to detect human Fhit by immunohistochemistry at dilutions up to 1:10,000. The Fhit protein expression was evaluated using both the intensity and extent of staining. Normal stratified squamous epithelium showed strong positivity, especially in the stratum spinosum and areas of keratinisation. Basal and parabasal cells were negative or expressed low levels of Fhit relative to the squamous epithelium. Mild and moderate epithelial dysplasia showed Fhit expression in the superficial layers, while Fhit expression was absent from severely dysplastic lesions. A reduction or loss of Fhit expression was found in 21 (66%) of the OSCC. The alterations in Fhit protein expression in OSCC, and not in normal tissues, are consistent with the proposal that Fhit inactivation plays a role in oral carcinogenesis.

Acid Anhydride Hydrolases↗

Risk for non-smoking-related cancer in atherosclerotic patients.

Some studies have suggested that the pathogenesis of atherosclerosis and that of cancer have common features, and in addition to tobacco smoking, oxidative stress, diet, and sex hormones have been considered as common etiological factors. To investigate whether there is an association between atherosclerosis and cancer, we evaluated the cancer pattern of patients with atherosclerosis of the aorta and of peripheral and cerebral vessels. A total of 69,485 patients with atherosclerosis were identified through the Danish National Registry of Patients between 1977 and 1989, and the incidence of cancer in this group was calculated by linkage to the Danish Cancer Registry for the period 1977-1993. No consistent excesses over the expected figures were seen for cancer at any site unrelated to tobacco smoking in either the total cohort or in subgroups. Specifically, we found no association at the individual level between atherosclerosis and colorectal cancers or hormone-related cancers, except from a decreased standardized incidence ratio of 0.7 (95% confidence interval, 0.5-0.9) for endometrial cancer. The standardized incidence ratio for cancers of the brain and nervous system was 1.1 (95% confidence interval, 0.9-1.3) for all patients combined, whereas patients with atherosclerosis of precerebral or cerebral arteries had a slightly increased risk (40%) for cancers of the brain and nervous system. The excess was seen only during the initial 3 years after discharge from hospital, and the likely explanation was a missed diagnosis. The study does not support the view that patients with atherosclerotic diseases represent a high-risk group for prostate cancer and potential future targets for prostate cancer screening interventions.

Aged↗

Cancer risk of patients discharged with acute myocardial infarct.

We studied whether common shared environmental or behavioral risk factors, other than tobacco smoking, underlie both atherosclerotic diseases and cancer. We identified a group of 96,891 one-year survivors of acute myocardial infarct through the Danish Hospital Discharge Register between 1977 and 1989. We calculated the incidence of cancer in this group by linking it to the Danish Cancer Registry for the period 1978-1993. There was no consistent excess over the expected figures for any of the categories of cancer not related to tobacco smoking. Specifically, the rates of colorectal cancer in acute myocardial infarct patients were similar to those of the general population, as were the rates for hormone-related cancers, including endometrial and postmenopausal breast cancers. We found a moderate increase in the risk for tobacco-related cancers, which was strongest for patients with early onset of acute myocardial infarct and for female patients. Overall, there do not seem to be major shared environmental or behavioral risk factors for acute myocardial infarct and cancers, except for smoking, and there seems to be no common inherited susceptibility to the development of these diseases.

Adult↗

[Causes of cancer in Scandinavia and possible preventive measures].

The purpose of this work is to address future possibilities for avoiding cancer. We elucidate the most important known causes of cancer in the Nordic countries during the second half of this century and provide estimates of the numbers of cancer cases that might be avoided by the year 2000 if those causes were effectively eliminated. Information on the pattern of carcinogenic exposures in each of the five Nordic countries and the associated relative risk estimates from the scientific literature were obtained. The numbers of avoidable cancers were assessed on the basis of this information together with the associated population attributable risk percent, PAR%, i.e. the proportion of a given cancer that can be avoided upon elimination of the causative factor. The main causes of cancer include smoking, alcohol consumption, exposure to occupational carcinogens, radiation, obesity and infection with human papillomavirus (HPV) and Helicobacter pylori. Annually, more than 18,000 cancers in men and 11,000 in women in the Nordic populations could be avoided by eliminating exposure to known carcinogens which is equivalent to 33 percent and 20 percent of all cancers arising in men and women, respectively, around the year 2000. Smoking habits account for a little more than half of these avoidable cases. Exposure to solar radiation, HPV and Helicobacter pylori, diagnostic and therapeutic radiation and consumption of alcohol play important roles in the causation of cancer, as each of these factors is linked with 1-5 percent of all cancers in men and women. Occupational exposures are also substantial causes in men (3 percent), and obesity is important in women (1 percent). In contrast, current knowledge is insufficient to give reliable estimates of the numbers of cancers that could be avoided by well-described modifications of dietary habits. These figures indicate that the most efficient way of reducing cancer morbidity would be to reduce the prevalence of exposure of the population to cancer-causing agents.

Carcinogens↗

Summary of avoidable cancers in the Nordic countries.

An overview is given of the most important known causes of cancer in the five Nordic countries and the resulting number of cancers that are potentially avoidable. The main causes include active and passive smoking, alcohol consumption, exposure to asbestos and other occupational carcinogens, solar and ionizing radiation, obesity, human papillomavirus infection in the female genital tract and infection with Helicobacter pylori. The organs most commonly affected are those of the respiratory system, the upper digestive tract and stomach, skin, the lower urinary tract and the uterine cervix. Annually, more than 18,000 cancers in men and 11,000 in women in the Nordic populations could be avoided by eliminating exposure to known carcinogens which is equivalent to 33% and 20% of all cancers arising in men and women, respectively, around the year 2000. Smoking habits account for a little more than half of these avoidable cases. Estimates of avoidable cancers are given for each Nordic country, separately.

Air Pollutants↗

Avoidable cancers in the Nordic countries. Tobacco smoking.

Active smoking is causally associated with cancers of the lung, larynx, oral cavity, pharynx, oesophagus, pancreas, renal parenchyma, renal pelvis and urinary bladder, and passive smoking appears to be causally associated with cancer of the lung. Information on smoking habits for the years 1965, 1975 and 1985 shows that more men than women in the Nordic countries were current smokers. The rates of women were stable over time and those of men were decreasing, approaching those of women. Lung cancer, in particular, is strongly associated with active smoking: by increasing the number of cigarettes smoked per day (lifelong) to 5, 10, 20 and 40 or more, the risk increases by five-, eight-, 16- and 30-fold, respectively, over that of people who have never smoked. Thus, with approximately 35% current smokers and 25% former smokers among Nordic men in 1985 and approximately 30% current smokers and 15% former smokers among Nordic women in that year, by the year 2000 10,000 cases of lung cancer (6,500 in men and 3,500 in women) will be caused by active smoking; this is equivalent to 82% of all cases of lung cancer in these populations. Another 6,000 cancers of other types (4,000 in men and 2,000 in women) are caused annually by active smoking, yielding a total of 16,000 new cases each year around the turn of the century. This implies that 14% (19% in men and 9% in women) of all incident cancers in the Nordic countries around the year 2000 will be caused by active tobacco smoking. In comparison, passive smoking is a minor cause of lung cancer, responsible for approximately 0.6% of all new cases (approximately 70 cases annually) in this area around the turn of the century.

Female↗

Avoidable cancers in the Nordic countries. Alcohol consumption.

Alcohol intake is causally associated with cancers of the larynx, oral cavity, pharynx, oesophagus and liver. In all five Nordic countries, alcohol consumption increased substantially between 1965 (6.5 litres per adult per year) and 1975 (10 litres), but remained at about 10 litres between 1975 and 1985. The daily consumption of men during the period was substantially higher than that of women, and that of both men and women was higher in Denmark than in the other Nordic countries. In about 2000, an annual total of almost 1,300 cancer cases (1,000 in men and 300 in women) would be avoided if alcohol drinking were eliminated. This corresponds to about 29% of all alcohol-related cancers, i.e. in the oesophagus (37%), oral cavity and pharynx (33%), larynx (29%) and liver (15%). About 2% of all cancers in men and 1% in women in the Nordic countries around the year 2000 will be caused by the drinking habits of the respective populations.

Alcohol Drinking↗

Avoidable cancers in the Nordic countries. Occupation.

A number of chemicals encountered predominantly in occupational settings have been causally linked with cancer in humans; furthermore, several industrial processes and occupations have been associated convincingly with increased rates of cancer, although the specific carcinogens remain to be identified. The tissues affected are mainly the epithelial lining of the respiratory organs (nasal cavity, paranasal sinuses, larynx and lung), and urinary tract (renal parenchyma, renal pelvis and urinary bladder), the mesothelial linings, the bone marrow and the liver. During the period 1970-84, almost 4 million people (3.7 million men and 0.2 million women) in the Nordic countries were potentially exposed to above-average levels of one or more verified industrial carcinogens. It is expected that these exposures will result in a total of about 1,900 new cases of cancer every year in the Nordic countries around the year 2000, with 1,890 among men and fewer than 25 among women. The proportions that could be avoided if industrial carcinogens were eliminated would be 70% of mesotheliomas, 20% of cancers of the nasal cavity and sinuses, 12% of lung cancers, 5% of laryngeal cancers, 2% of urinary bladder cancers, 1% of the leukaemias, and 1% of renal cancers. Overall, it is estimated that verified industrial carcinogens will account for approximately 3% of all cancers in men and less than 0.1% of all cancers in women in the Nordic countries around the year 2000. No attempt was made to estimate the potential effects of suspected carcinogens in the workplace.

Air Pollutants, Occupational↗

Avoidable cancers in the Nordic countries. External environment.

Air pollutants arising from traffic clustering and industrial production include a number of chemical compounds that at high doses are carcinogenic in animal models and in some instances also in humans. Direct epidemiological evidence for a carcinogenic effect of air pollution in humans is, however, weak, and most of the available studies are limited by lack of adequate control of confounding factors and other methodological drawbacks. Limited evidence exists for a link between urban air pollution and lung cancer, with reported relative risks of 1.0-1.5. About one-third of the population of the Nordic countries, corresponding to 7.3 million people, lives in urban areas. If there is an excess risk associated with air pollution, the annual number of lung cancer cases around the year 2000 in the Nordic countries would range from 0 (no excess risk) to 1,800 (relative risk, 1.5). As the existence of a causal link between air pollution and cancer is not uncorroborated, measures for avoiding cancer from this source cannot be recommended.

Air Pollutants↗

Avoidable cancers in the Nordic countries. Radiation.

Exposure to solar and ionizing radiation increases the risk for cancer in humans. Some 5% of solar radiation is within the ultraviolet spectrum and may cause both malignant melanoma and non-melanocytic skin cancer; the latter is regarded as a benign disease and is accordingly not included in our estimation of avoidable cancers. Under the assumption that the rate of occurrence of malignant melanoma of the buttocks of both men and women and of the scalp of women would apply to all parts of the body in people completely unexposed to solar radiation, it was estimated that approximately 95% of all malignant melanomas arising in the Nordic populations around the year 2000 will be due to exposure to natural ultraviolet radiation, equivalent to an annual number of about 4700 cases, with 2100 in men and 2600 in women, or some 4% of all cancers notified. Exposure to ionizing radiation in the Nordic countries occurs at an average effective dose per capita per year of about 3 mSv (Iceland, 1.1 mSv) from natural sources, and about 1 mSv from man-made sources. While the natural sources are primarily radon in indoor air, natural radionuclides in food, cosmic radiation and gamma radiation from soil and building materials, the man-made sources are dominated by the diagnostic and therapeutic use of ionizing radiation. On the basis of measured levels of radon in Nordic dwellings and associated risk estimates for lung cancer derived from well-conducted epidemiological studies, we estimated that about 180 cases of lung cancer (1% of all lung cancer cases) per year could be avoided in the Nordic countries around the year 2000 if indoor exposure to radon were eliminated, and that an additional 720 cases (6%) could be avoided annually if either radon or tobacco smoking were eliminated. Similarly, it was estimated that the exposure of the Nordic populations to natural sources of ionizing radiation other than radon and to medical sources will each give rise to an annual total of 2120 cancers at various sites. For all types of ionizing radiation, the annual total will be 4420 cancer cases, or 3.9% of all cancers arising in the Nordic populations, with 3.4% in men and 4.4% in women.

Female↗