Cancer risk among Danish male Seventh-Day Adventists and other temperance society members.

Cancer risk was studied in 781 male Seventh-Day Adventists (SDA) and 808 male members of other temperance societies. Standardized morbidity ratios for all cancers were 0.69 among SDA and 1.05 among other temperants. Significantly decreased risks of cancers were noted among SDA for cancer of the colon [observed/expected (O/E): 0.13], cancer of the respiratory system (O/E: 0.17), cancer of the lung (O/E: 0.15), and cancer of the bladder including papilloma (O/E: 0.13). No significant deviations from expectations were noted among members of other temperance societies. Thus risks of tobacco-associated cancers were markedly decreased among SDA. The risk of alcohol-associated cancers (cancers of the oral cavity, pharynx, esophagus, and larynx) taken together was also decreased (O/E: 0.7), although not significantly so. When the results were compared with those of a previous study of Danish brewery workers who had a high average daily beer intake, the present investigation provides further support that the alleged association between beer consumption and the occurrence of rectal cancer is of a noncausal nature. The explanation for the decreased risk of colon cancer should probably be sought in the dietary practices of SDA.

Trends in the incidence of leukemia in Denmark, 1943-77: an epidemiologic study of 14,000 patients.

An epidemiologic study of the total population of patients with leukemia in Denmark during 1943-77 was performed with special emphasis on time trends. The material stemmed from the national Danish Cancer Registry and was believed to be virtually complete. Of the 13,813 patients, 40% had acute leukemia; 40%, chronic lymphocytic leukemia; patients, 40% had acute leukemia; 40%, chronic lymphocytic leukemia; and 20%, chronic myeloid leukemia. Over the 35-year period, the incidence of acute leukemia increased threefold in the age groups 0-9 and 50-70+ years; whereas the increase in the age group 0-9 years climaxed in the 5-year period 1968-72, and the increase in the age group 50-70+ years was sustained. The incidence of chronic lymphocytic and chronic myeloid leukemia remained unchanged. No geographic pattern was discernible.

Cancer incidence and mortality in workers exposed to fluoride.

BACKGROUND: Although a recent bioassay showed increased frequency of bone cancer in rats with high oral intake of fluoride, the data are reported as equivocal evidence of carcinogenicity. In humans, occupational fluoride exposure may cause skeletal fluorosis, and our earlier follow-up of fluoride-exposed workers showed increased incidence of respiratory cancers. PURPOSE: To further evaluate occupational fluoride exposure as a carcinogenic risk factor, we extended by approximately one decade the follow-up of a cohort of 425 men and 97 women employed for at least 6 months in the period 1924-1961 at the Copenhagen cryolite processing plant. Cryolite ore contains about 50% fluoride. METHODS: Cancer mortality was determined for the period 1941-1989, and incidence for 1943-1987. For comparison, we used national mortality rates and cancer incidence rates for the Copenhagen area. RESULTS: Among the men, 300 deaths occurred; 223 were expected. Respiratory (lung and laryngeal) cancers and violent death were responsible for most of this excess; rates for mortality from cardiovascular disease were close to the rates expected. Of the 423 male workers, 119 developed cancers; 103.6 were expected. There was excess incidence of cancers of the lungs (35 men; standard incidence ratio [SIR] = 1.35), larynx (5 men; SIR = 2.29), and urinary bladder (17 men; SIR = 1.84). Maximum incidence occurred after 10-19 years of employment, but otherwise, no stable relationship between cancer incidence and duration of employment was observed. The incidence of respiratory and urinary cancers was particularly high in men less than 35 years old at first employment. Cancers in female workers were too few to allow detailed evaluation. CONCLUSIONS: The increased incidence of respiratory cancers suggests that cigarette smoking was frequent in this cohort, despite the unremarkable cardiovascular mortality, but the disproportionate increase in the incidence of bladder cancer is difficult to explain by smoking habits alone. Because this industrial cohort was exposed to high concentrations of fluoride dust, heavy respiratory exposure to fluoride may have contributed to the increased cancer risk. If these workers inhaled a carcinogenic substance partly excreted in the urine, an increased incidence of respiratory and bladder cancers would not be inconceivable. IMPLICATION: The potential role of fluoride as a cause of bladder cancer needs to be explored.

Endogenous nitrosation in relation to nitrate exposure from drinking water and diet in a Danish rural population.

Increasing levels of nitrate in drinking water is of concern due to the possibility of an associated increase in long-term exposure to endogenously formed carcinogenic N-nitroso compounds. Excretion of N-nitrosoproline in 12-h overnight urine after intake of 500-mg L-proline was used to quantify the rate of endogenous nitrosation in 285 individuals in an area in northern Denmark with large variation in nitrate concentration of the drinking water. Nitrate intake was measured in a 24-h duplicate diet sample. The crude association between nitrate concentration in drinking water and rate of endogenous nitrosation in individuals is only weakly positive and not quite statistically significant (P = 0.08). The risk of having detectable nitrosation increases significantly with total nitrate intake and tobacco smoking. In nonsmokers, nitrosation is determined by nitrate intake. Smokers have increased nitrosation which does not depend on nitrate intake. Effect modification through dietary factors was evaluated and indicated a protective effect of tea consumption, while the effect of eating vegetables was not clear-cut. The experimental design (12-h urine sample; proline dose taken in the evening) is likely to underestimate the effect of nitrate in drinking water relatively to nitrate in the diet.

Immunoelectron microscopy studies on the modulation of common acute lymphoblastic leukemia antigen (CALLA) on NALM-6 cells: delineation of intracellular transport.

Even though much is known about the presence of the common acute lymphoblastic leukemia antigen (CALLA) with respect to its distribution in hematopoietic and non-hematopoietic tissues, its functional role in lymphoid cells is as yet unknown. Given the fact that CALLA is completely modulated on the surface of lymphoid cells, we have employed pre-embedding immunogold techniques at electron-microscopical level and demonstrated that J5 monoclonal antibody (MoAb)-mediated modulation of CALLA expression on the lymphoblastic cell line NALM-6 is a specific, rapid process, closely resembling receptor-mediated endocytosis. Furthermore, it was found that CALLA was internalized through plasmalemmal pits and cytoplasmic vesicles and processed intracellularly in multivesicular bodies and secondary lysosomes. In contrast, HLA-DR antigen remained at the cell surface upon contact with specific MoAb. These data suggest that CALLA might be a receptor for a hitherto unknown signal molecule.

Diet, transit time, stool weight, and colon cancer in two Scandinavian populations.

In samples of adult men from two Scandinavian populations with 4-fold differences in colon cancer incidence, a comparison was made of estimated food records over 4 days, defecation habits, mouth-to-anus transit time, and stool weight. The "high incidence" group consumed more white wheat breads and total meat and beer, but less potatoes and milk than the "low incidence" group. Defecation habits were similar. Transit time and stool weight had few significant correlations with diet and defecation habits, but stool weights were higher in the low incidence group. The results are consistent with a possible protective role of dietary fiber, unrelated to transit time.

Cancer in the European Community and its member states.

The European Community (EC) mounted the "Europe Against Cancer" programme in 1987 to control cancer. Information on mortality rates is available for all member countries and the incident number of cancers was estimated for each site, for each country and for the EC as a whole. In 1980 there were 730,000 deaths from cancer and an estimated 1,222,120 [corrected] new cases (excluding non-melanoma skin cancers). Among men, cancer of the lung is the leading cancer site with some 135,000 cases per year followed by prostate, colon and bladder cancer. Breast cancer is the leading site in women, with 135,000 cases per year, followed by colon, stomach and genital cancer. Among men, melanoma of the skin, and lung, pancreas and rectum cancer are more frequent in the north in contrast to larynx, oesophagus, buccal cavity and liver cancer, which are more frequent in the south. There are additional contrasts between Southern European countries. The contrasts are less striking for women. This study provides an estimate of the true number of cases only. The establishment of a network of European cancer registries should eventually lead to more comprehensive incidence information form the EC.

Parental employment at time of conception and risk of cancer in offspring.

Studies on the possible association between exposures of parents at the time off conception and cancer in their offspring have provided no clear answer. In this large, population-based, record-linkage study, 1747 childhood cancer cases were identified in the Danish Cancer Registry and matched with 8630 population controls. Specific information on the employment held by each parent at the time of conception and during early pregnancy was obtained through record linkages. The most recent job titles of the parents were also supplied. Significantly increased risks for renal cancer (mainly Wilms' tumour) and for osteogenic and soft tissue sarcomas were observed in children in association with mothers' employment in medical and dental care, based on 15 observations and odds ratios (OR) of 2.5-4.0. The risk for cancers at all sites was significantly elevated in children of female nurses (OR = 1.4; n = 75) and of male and female physicians, dentists, dental assistants, veterinarians and pharmacists combined (OR = 1.4; n = 53). Handling of drugs, exposure to anaesthetics and infections during pregnancy are suggested to be potential risk factors. Significantly increased risks were also observed for children of fathers employed in the manufacture of iron and metal structures (OR = 2.2; n = 16), in machine repair workshops (OR = 2.8; n = 6), as machinists (OR = 1.6; n = 47) and as smiths (OR = 1.5; n = 28). The suggestion in earlier studies that exposures to hydrocarbons and lead are risk factors for childhood cancer could not be supported by our analysis. Overall, few associations were observed; it was therefore concluded that parental occupation is not likely to be a major risk factor for childhood cancer.

Prognostic factors in soft tissue sarcomas: the Aarhus experience.

In the present study, the outcome, patterns of local recurrence and survival, as well as prognostic factors, were evaluated in patients surgically treated for soft tissue sarcomas. Between January 1979 and July 1993, 316 consecutive patients were referred to the Sarcoma Centre in Aarhus with localised malignant soft tissue sarcoma of the extremities or trunk. If possible, the patients were treated with a limb-sparing resection, primarily by use of a wide excision. 50 patients received adjuvant radiotherapy. There were 161 men (51%) and 155 women (49%) median age 56 years (range 1-94 years). 94 patients (30%) had tumours in the trunk, including shoulder and buttock lesions, 163 (52%) in the lower extremity and 59 (19%) in the upper extremity. 52 patients (16%) had grade 1 tumour, 60 (19%) grade 2 and 204 (65%) grades 3A-3B. The 5-year local recurrence rate was 18% and the 5-year survival rate was 75%. Multivariate analysis indicated the following variables as independent unfavourable factors for local recurrence: extracompartmental location, histological high grade, local excision, no adjuvant radiotherapy and intralesional/marginal excision. Independent unfavourable factors for survival were advanced age, extracompartmental location, histological high grade, lower extremity location and large tumour size. If the variable local recurrence was included in the analysis, it was found to have a very strong influence on survival. Based on these variables, a prognostic model was developed.

Conjugation to preactivated proteins using divinylsulfone and iodoacetic acid.

Two methods for the preactivation of proteins and conjugation of peptides to proteins under mild conditions are presented. Preactivation of proteins with divinylsulfone (DVS) permits peptide conjugation through either amino, hydroxyl or sulphydryl groups depending on the coupling pH used, while preactivation with iodoacetic acid (IAA) N-hydroxy-succinimide ester permits selective conjugation through sulphydryl groups. In addition, the latter method allows quantitation of the conjugation ratio through determination of carboxymethyl cysteine after acid hydrolysis. The divinylsulfone activated proteins can be stored for extended periods of time at -20 degrees C until required for conjugation, while the iodoacetic acid activated protein can be stored for a few days at -20 degrees C. These conjugation methods were investigated with respect to obtaining peptide/protein conjugates for immunization purposes and for use as reagents in immunoassays. The DVS activated proteins permitted direct conjugation of luteinizing releasing hormone (LHRH) through its tyrosine side chain and allowed synthesis of well defined conjugates. The DVS derivatives of bovine serum albumin (BSA), reduced and carboxymethylated BSA and purified protein derivative (PPD) were compared with respect to their potential value as carriers for obtaining antibodies to LHRH (M(r) 1000) and epidermal growth factor (EGF, M(r) 5000). IAA-PPD was evaluated as a carrier for the conjugation of glutathione specifically through its cysteine side chain and for obtaining antibodies to glutathione. The antisera obtained were specific and of high titer, and the methods described here will thus allow the convenient synthesis of carrier conjugates with well defined characteristics.

The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas.

PURPOSE: In malignant tumors the oxygenation status and tumor cell proliferation are known to influence local tumor control after radiotherapy. However, the relationship between oxygenation status and tumor cell kinetics in human tumors has not yet been described. Newly developed clinically applicable techniques such as oxygen electrode measurements and assessment of tumor cell proliferation rates have been suggested as promising predictive assays. The purpose of the present study was to characterize tumor oxygenation status in soft tissue sarcomas and to compare this with tumor cell kinetics and clinical parameters. METHODS AND MATERIALS: Pretreatment tumor oxygenation status was measured by polarographic oxygen needle electrodes and evaluated as the median pO2 and the percentage of pO2 values < or = 5 mmHg and < or = 2.5 mmHg in 22 patients with primary soft tissue sarcomas. All tumors were characterized by histology, grade of malignancy, the level of microscopic necrosis, the level of effective hemoglobin, and magnetic resonance imaging estimation of tumor volume. The tumor cell potential doubling time and labeling index were measured by flow cytometric and immunohistochemical analysis of tumor biopsy specimens after in vivo incorporation of iododeoxyuridine. RESULTS: There was a significant correlation between the median pO2 and the tumor cell potential doubling time (p = 0.041), whereas no correlation was found between the level of hypoxia expressed by the percentage of pO2 values < or = 2.5 and < or = 5 mmHg, respectively, and tumor cell potential doubling time. Furthermore, no correlation was found between either of the three tumor oxygenation parameters and labeling index. The material represented large intertumor heterogeneity in oxygenation status, cell kinetics, and tumor volume, and no correlation was found between oxygenation status and either volume, histopathology, grade of malignancy, or effective hemoglobin. CONCLUSION: This report is the first to suggest a correlation between tumor oxygenation and tumor cell doubling time, as the fastest proliferating tumor cells were found in the poorest oxygenated soft tissue sarcomas. More data are needed to clarify if this relation is really a true biological phenomenon. Furthermore, tumor oxygenation status of soft tissue sarcomas was heterogeneous and independent of clinical and histopathological parameters.

Modulation and intracellular transport of CD20 and CD21 antigens induced by B1 and B2 monoclonal antibodies in RAJI and JOK-1 cells--an immunofluorescence and immunoelectron microscopy study.

By fluorescence microscopy (FM), flow cytometry (FCM) and immunoelectron microscopy (IEM) we have shown that B1 and B2 monoclonal antibodies (MoAbs) were able to induce modulation of CD20 and CD21 in RAJI and JOK-1 cell lines. Redistribution and internalization of both antigens (Ags) after binding with MoAbs was readily demonstrated by FM, and by IEM CD20 and CD21 were found to be processed by the pathway of receptor-mediated endocytosis. The rate of intracellular transport varied: CD21 > CD20 and RAJI > JOK-1. Approximately 65 and 55% of CD20 and 60 and 45% of CD21 were cleared from the surface of RAJI and JOK-1 cells, respectively (FCM and IEM). These values, however, clearly exceeded those corresponding to internalization (11, 9, 24 and 16%) indicating shedding of Ag-MoAb complexes. No evidence of recycling was found. The present data support the hypothesis that the kinetics of modulation vary from one Ag to another and probably also reflect the stage of differentiation of the malignant B-cells. The results are discussed in the context of the possible usefulness of B1 and B2 MoAbs in the therapy of B-cell malignancies.

In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: a cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients.

Of 560 consecutive, newly diagnosed untreated patients with B CLL submitted for chromosome study, G-banded karyotypes could be obtained in 480 cases (86%). Of these, 345 (72%) had normal karyotypes and 135 (28%) had clonal chromosome abnormalities: trisomy 12 (+12) was found in 40 cases, 20 as +12 alone (+12single), 20 as +12 with additional abnormalities (+12complex). Other frequent findings included abnormalities of 14q, chromosome 17, 13q and 6q. The immunophenotype was typical for CLL in 358 patients (CD5+, Slg(weak), mainly FMC7-) and atypical for CLL in 122 patients (25%) (CD5-, or Slg(strong) or FMC7+). Chromosome abnormalities were found significantly more often in patients with atypical (48%) than in patients with typical CLL phenotype (22%) (P < 0.00005). Also +12complex, 14q+, del6q, and abnormalities of chromosome 17 were significantly more frequent in patients with atypical CLL phenotype, whereas +12single was found equally often in patients with typical and atypical CLL phenotype. The cytomorphology of most of the +12 patients was that of classical CLL irrespective of phenotype. In univariate survival analysis the following cytogenetic findings were significantly correlated to a poor prognosis: chromosome 17 abnormalities, 14q+, an abnormal karyotype, +12complex, more than one cytogenetic event, and the relative number of abnormal mitoses. In multivariate survival analysis chromosome 17 abnormalities were the only cytogenetic findings with independent prognostic value irrespective of immunophenotype. We conclude that in patients with typical CLL immunophenotype, chromosome abnormalities are somewhat less frequent at the time of diagnosis than hitherto believed. +12single is compatible with classical CLL, and has no prognostic influence whereas chromosome 17 abnormalities signify a poor prognosis. In patients with an atypical CLL immunophenotype, chromosome abnormalities including +12complex, 14q+, del 6q and chromosome 17 are found in about 50% of the patients, and in particular chromosome 17 abnormalities suggest a poor prognosis.

Risk of kidney cancer in analgesics users.

The risk of kidney cancer was examined in a cohort of people discharged from Danish hospitals from 1977-1987 with a diagnosis of rheumatoid arthritis, osteoarthrosis or backpain. These individuals are presumably more or less regular users of mild analgesics. A total of 155,554 people were identified. The risk of cancer of the urinary tract was slightly increased [relative risk (RR) = 1.31], almost exclusively because of an increased risk of renal cell carcinoma (RR = 1.40). The relative risk was higher in individuals with rheumatoid arthritis than among individuals with osteoarthrosis or backpain, and higher among women than men. Although this study lacks information on the actual analgesics consumption of the individual, and various biases may be present, these findings offer little support to the concern that increased analgesics use raises the risk of kidney cancer.

Gross examination of musculoskeletal sarcomas. Estimation of tumour volume and sampling for unbiased morphometry.

A method for handling and gross examination of specimens from musculoskeletal sarcomas is described. The method, which can be modified to relate to modern, preoperative tumour imaging, allows an accurate estimation of tumour volume and a systematic random sampling for morphometry, which for instance permits the unbiased estimation of tumour necrosis, cellularity and mitotic index. Furthermore, sampling can be performed in such a way that stereological parameters (for the estimation of nuclear size and pleomorphism) based on 'vertical sections' can be measured. The method in no way prohibits routine sampling, for instance from specimen margins and specific areas of interest within the tumour, and with a little practice does not take much extra time.

Inhibition of plasmid-encoded adhesion of Yersinia enterocolitica by non-immunoglobulin fraction of human milk.

The inhibitory effect of human milk on plasmid-encoded adhesion of Yersinia enterocolitica to rabbit ileal brush border membrane vesicles immobilized on polystyrene was evaluated. Adhesion was reduced to about 50% after incubation of equal volumes of bacteria and undiluted human milk, but a significant reduction was also detectable after incubation with milk samples at a final 1:10 dilution. Removal of immunoglobulins from human milk by means of immunoadsorption did not change the inhibitory effect on adhesion. Both milk fat, proteins, and factors resistant to proteolytic and heat treatment contributed to the reduction in adhesion.

Trends in cutaneous malignant melanoma in Denmark 1943-1982 by anatomic site.

Time trends in the incidence of cutaneous malignant melanoma were examined by analysing data from the Danish Cancer Registry, 1943-1982, by sex and subsite for 3509 male and 5305 female cases. The age-standardized incidence rate for cutaneous malignant melanoma for men and women in Denmark increased by five- to six-fold between 1943 and 1982. The increase varied by site; a particularly pronounced elevation was seen for tumours of the trunk in both men and women and of the leg in women. A statistical analysis of the effects of age, time and cohort showed steep increases in risk for progressively younger birth cohorts. This association was particular pronounced for sites other than the face, scalp and neck; for the latter sites, there was a much smaller increase for younger cohorts.

Development of a semiquantitative food frequency questionnaire to assess food, energy and nutrient intake in Denmark.

Foods to be included in a Danish self-administered semiquantitative food frequency questionnaire were identified from food tables developed, together with data collected, for the survey 'Dietary habits in Denmark, 1985'. The questionnaire was to be used in a prospective study on diet, cancer and health, and the aim was to rank individuals with regard to intake of 19 different nutrients considered of prime importance in human carcinogenesis. The questionnaire for the dietary survey included 247 foods and recipes. From stepwise multiple regression analyses with the intake of each of the 19 nutrients as the dependent variable and the intake of the 247 foods and recipes as independent variables, the foods in the models explaining 90% of the between-person variability were considered for the final questionnaire. All relevant analyses were performed for the study group as a whole, for men and women separately, and in each gender for subgroups of energy intake. Taken together, the models explaining 90% of the between-person variability identified a total of 74 foods or recipes, which were important predictors of the intake of one or more of the nutrients considered. A few foods were excluded and a few foods were added to the final questionnaire based on common biological background information, and on information on foods providing important amounts of given nutrients, but which failed to contribute to regression analyses. The 92 foods and recipes, which were included in the final questionnaire provided altogether 81% of the average total supply of the nutrients.(ABSTRACT TRUNCATED AT 250 WORDS)

The pattern of cancer in a large cohort of stroke patients.

A cohort of 113,732 stroke patients from Danish Hospital Discharge Registry were, by linkage to the Danish Cancer Registry, found to have developed a total of 5151 cases of cancer in a mean follow-up time of 2.4 years after the diagnosis of stroke. There was no excess of gastric cancer. The present findings fail to support the existence of a common, strong risk factor for stroke and gastric cancer in individuals. In the cohort, more cancer than expected was observed. In particular, a more than ten-fold increase in risk of brain tumours within the first year after stroke diagnosis was observed, suggesting some diagnostic misinterpretation of a brain tumour as a stroke. Minor excesses of cancer of other sites were also found in the first year of follow-up. They are probably due to increased medical surveillance and diagnostic misinterpretation of an underlying malignancy as an incident of cerebrovascular disease, eg through metastatic spread to the brain.

Validation of a semiquantitative food frequency questionnaire developed in Denmark.

In 1989, a self-administered food frequency questionnaire, including 92 food items and 40 portion-size photographs, was validated against two times seven days of weighed diet records. A total of 144 subjects, aged 40-64 years, from the general population in Copenhagen were included. Correlations between mean calorie-adjusted intakes from the two-week diet records and the food-frequency questionnaire ranged from 0.27 for vitamin A to 0.71 for calcium. In general, higher correlation coefficients were observed for men than for women. On average, about 70% of subjects were classified in the same (+/- 1) quintile in the food frequency questionnaire and the diet records. Of those subjects belonging to the lowest quintile, estimated from the diet records, 42% fell in the same quintile and 68% into the lowest two quintiles in the food frequency questionnaire. Findings were similar for the upper tail of the distribution. Gross misclassification, observed in the highest and lowest quintile, was found for 4% and 7% of the subjects, respectively. It is concluded that this food frequency questionnaire is a useful instrument for categorizing individuals according to their intake of nutrients and energy.