Expression of matrix metalloproteinase-2 in serous borderline ovarian tumors is associated with noninvasive implant formation.

OBJECTIVE: To investigate matrix metalloproteinase (MMP) proteolytic and vascular endothelial growth factor (VEGF) and receptor (VEGFR-1, VEGFR-2) angiogenetic capacity in serous borderline ovarian tumors (S-BOTs) for women with and without noninvasive implants. METHODS: The population was made up of 99 patients with S-BOTs as the primary diagnosis between 1985 and 1995, 44 of whom had noninvasive implants and 55 without implants. MMP-2, MMP-14, the type-2 tissue inhibitor of MMPs (TIMP-2), and VEGF and receptors (VEGFR-1, VEGFR-2) were examined by immunhistochemistry. RESULTS: Strong positive (+++) MMP-2 staining was found more frequently in women with primary S-BOTs and noninvasive implants (76%) than in those without implants (53%; p < 0.05). In contrast, staining for MMP-14 and TIMP-2 was not significantly different in the two groups. Furthermore, expression of MMP-2, MMP-14, and TIMP-2 was similar in primary tumors and in their noninvasive implants. Most tumors in both groups had no VEGF expression (84% in the noninvasive implant group and 82% in the group without implants), while moderate (++) to strong (+++) expression of VEGFR-1 and VEGFR-2 was detected in 79% and 94% of the two tumor groups, with no significant difference between the groups. CONCLUSIONS: Enhanced MMP-2 was seen in primary S-BOT with noninvasive implants. The presence of noninvasive implants was prognostic for disease-free survival.

Survival and causes of death in thyroid cancer: a population-based study of 2479 cases from Norway.

Survival and prognostic factors were studied in 2479 clinically presenting thyroid cancers (TC) reported from the entire Norwegian population from 1970 to 1985. Complete follow-up was obtained (median, 48 months), with information on causes of death. At the end of the observation period, 498 patients were reported to have died of TC, representing 69.7% of all deaths. Among 216 patients dying of other main causes, TC was considered to be a contributing cause of death in 80 cases (11.2%). Multivariate regression analysis of TC deaths showed no significant difference according to sex in any of the histological types. Age had a strong impact on survival, and for papillary carcinomas this effect was apparent after the age of 55 years. Marked differences were observed between various histological types, even between papillary and follicular carcinomas when interactions were included. Furthermore, tumor stage was a strong predictor of TC deaths, and a reduced survival was also found in patients with lymph node metastases. In conclusion, the importance of age, histological type, and tumor stage as major prognostic factors has been documented in this population-based study from Norway.

Cancer in the Sami population of North Norway, 1970-1997.

The Sami population in North Norway constitutes an ethnic minority with a lifestyle that diverges from that of the rest of the population. A cohort of 19 801 people of Sami origin was followed for cancer incidence over the period 1970-1997 by the Norwegian Cancer Registry. Among the Sami 1340 cases of cancer were observed versus 1658.2 expected, based on a regional reference population. For both sexes a significantly decreased incidence of colon cancer was observed. The standardized incidence ratio (SIR) for men was 0.50 (95% confidence interval (CI) 0.34-0.71) and for women 0.62 (95% CI 0.43-0.85). Low SIRs were observed for lung cancer: 0.63 (95% CI 0.51-0.77) and 0.60 (95% CI 0.37-0.91), for men and women, respectively. Men of Sami ancestry had a decreased risk of prostate cancer: SIR 0.57 (95% CI 0.45-0.71). Among women 127 cases of breast cancer were observed versus 149.6 expected. A relatively high physical activity and a diet rich in fish may in part explain the low cancer incidence. Some Sami were exposed to radioactivity as a result of their diet based on reindeer products. Adverse effects on their cancer incidence were not observed.

The influence of mammographic screening on national trends in breast cancer incidence.

Introducing an organized mammographic screening programme affects the breast cancer incidence rate in a population. The diagnosis is advanced in time, and initially, an increase will occur in the number of cases, followed by a drop in the rate when women leave the programme. The aim of this study was to quantify the potential effects that mammographic screening programmes have on breast cancer incidence. In addition, we wanted to investigate how the incidence of breast cancer varies between different birth cohorts, age groups and time periods in the five Nordic countries Finland, Denmark, Iceland, Norway and Sweden, adjusting for the effects of the screening programmes. Time trends were analysed over the period 1978-1997, using age-period-cohort models. In Sweden, the rates more than doubled (relative risk (RR)=2.20, 95% confidence interval (CI) 1.8-2.6) in women offered screening for the first time compared with women not offered screening. The risk remained elevated (RR=1.34, 95% CI 1.2-1.6) for women who were continued to be offered screening, compared with women who were not offered screening. Finally, the rates dropped (RR=0.68, 95% CI 0.6-0.8) when the women left the programme. This indicates that screening advances the time of diagnosis, which is a prerequisite to subsequent reduction in mortality. Analysis of secular trends, corrected for the influence of screening, showed that the rates in Finland increased by 13% per 5-year period, with a more modest increase in the other countries. There were strong cohort effects in all Nordic countries, and the risk seemed to be flattening for the youngest cohorts in most of the countries.

Sandostatin LAR in acromegalic patients: a dose-range study.

Sandostatin LAR is a sustained release formulation of octreotide that has been developed by microencapsulating the drug with biodegradable poly(lactide-glycolide)-glucose. We have investigated the efficacy and tolerability of Sandostatin LAR given as a single dose im to patients with active acromegaly who showed good GH suppression during a 2- to 4-week pretreatment period with octreotide given sc. Two double blind studies were performed. Initially, 14 patients were randomized and observed over 42 days after a single im injection of 3, 6, 9, or 12 mg Sandostatin LAR. In the second study, 15 patients were randomized and observed over 60 days after a single im injection of either 20 or 30 mg Sandostatin LAR. Assessments of 12-h GH and octreotide profiles and adverse events were made on day -14 (during treatment with Sandostatin, sc); day 0 (off treatment after wash-out period); days 1, 7, 14, 21, 28, 35, and 42; and, for study 2, also on days 49 and 60 after the im injection. Only injections of 20 or 30 mg were followed by a suppression of basal GH and insulin-like growth factor I to levels comparable to those seen during sc treatment. The suppression of mean GH to less than 5 micrograms/L lasted for 4 weeks in the group receiving 20 mg and for at least 6 weeks in those given 30 mg Sandostatin LAR. The pharmacokinetic profile fitted a biphasic drug release model previously described for peptides in similar drug delivery systems. Serum concentrations correlated with the im administered dose. Suppression of GH and insulin-like growth factor I was achieved at serum octreotide concentrations exceeding approximately 600 ng/L. Tolerability was good. Sandostatin LAR holds promise as a valuable drug for the treatment of acromegaly. The results of ongoing long term studies will provide further necessary knowledge of the drug.

Thyroid cancer in children in Norway 1953-1987.

All cases of thyroid cancer in children aged 15 years or younger registered in Norway (1953-1987) are presented. 30 girls and 5 boys are included, the youngest being a 6-year-old boy. Half of the patients were in the age-group 14-15 years. As for adults, papillary thyroid cancer was most common. 70% of the patients presented with tumour growth outside the thyroid gland. In spite of this, only 2 children died of the disease during the follow-time (maximum 37 years).

Incidence of thyroid cancer in Norway 1970-1985. Population review on time trend, sex, age, histological type and tumour stage in 2625 cases.

In the Norwegian population, a total of 1977 females and 648 males had a diagnosis of thyroid cancer and were reported to the Cancer Registry during 1970-85. Most of the cases (98%) were histologically or cytologically confirmed, and 141 cases were diagnosed at autopsy (5.4%). Of the patients with information available, 13% had not been subjected to radical surgery. The actual number and annual incidence rate of thyroid cancer increased during the period, especially among females, although a possible levelling off was observed at the end. The frequency of papillary carcinoma clearly increased with time, and tumours were more often localized at presentation in later years. Improved detection of smaller tumours and differences in histopathological judgement may in part explain these results, but our findings are so notable that etiological factors must also be accounted for and researched. Associations between sex, age, histology and stage were further studied in a multivariate log-linear model. The results confirm the importance of sex and age when exploring the observed incidence pattern and also show that various histological types are unique with respect to metastatic patterns, when confounding factors have been adjusted for.

Cohort analysis of cigarette smoking and lung cancer incidence among Norwegian women.

BACKGROUND: Cancer registries have for decades surveyed the development of cancer diseases. Data on incident cases includes demographic variables. Knowledge of the temporal distribution of risk factors on the same variables makes it possible to model the relationship between disease and risk factor. The results of such analyses might be difficult to interpret since they are based on aggregated data. But the availability of these data sources should encourage further exploration of its possibilities and limitations. METHODS: The temporal pattern of smoking habits in 5-year birth cohorts from 1890-1949 was established, with data on the proportions of current smokers, former smokers and non-smokers and estimated average daily consumption of tobacco and average duration of smoking. The lung cancer incidence among the cohorts in 1953-1992 was analysed by a model which included an additive excess risk for smokers that depended on daily dose and duration of smoking. RESULTS: The lung cancer incidence in later decades was adequately described by the model, which showed a simple relationship with smoking behaviour in the cohorts. For both current smokers and former smokers, the excess risk was about proportional to the daily amount smoked and the 4.5 power of duration of smoking. The age-specific rates for non-smokers were close to a fifth-power curve of age. CONCLUSIONS: Even if lung cancer incidence is not determined separately for groups with known smoking habits, plausible estimates of the effect of smoking can be derived if appropriate information is available on temporal smoking habits in the population.

Cancer incidence among Norwegian airline cabin attendants.

BACKGROUND: Cabin crews are exposed to cosmic radiation at work and this may increase their incidence of radiation-induced cancers. Former studies indicate an increased risk of breast cancer. METHODS: A retrospective cohort study was performed. The cohort was established from the files of the Civil Aviation Administration and included people with a valid licence as a cabin attendant between 1950 and 1994. The cohort was linked to the Cancer Registry of Norway. Observed number of cases was compared with expected, based on national rates. Breast cancer incidence was analysed, adjusting for individual fertility variables. RESULTS: A group of 3693 cabin attendants were followed over 72 804 person-years. Among the women, 38 cases of breast cancer were observed (standardized incidence ratio (SIR) = 1.1, 95% CI : 0.8-1.5). Among men excess risks were found for cancers in the upper respiratory and gastric tract (SIR = 6.0, 95% CI : 2.7-11.4) and cancer of the liver (two cases, SIR = 10.8, 95% CI : 1.3-39.2). For both sexes elevated risks were found for malignant melanoma and non-melanoma skin cancer; for men these were SIR = 2.9 (95% CI : 1.1-6.4) and SIR = 9.9 (95% CI : 4.5-18.8) respectively, while for women these were SIR = 1.7 (95% CI : 1.0-2.7) and SIR = 2.9 (95% CI : 1.0-6.9) respectively. For no cancer site was a significant decreased risk found. CONCLUSIONS: An increased risk of radiation-induced cancers was not observed. The excess risks of some other cancers are more probably explained by factors related to lifestyle.

Prediagnostic serum selenium in a case-control study of thyroid cancer.

Sera from 43 persons who developed thyroid cancer on an average 4.8 years after blood sampling were compared with sera from controls. Three controls per case matched for sex, age, place of residence and year of blood sampling, with regard to serum selenium and serum copper. Cases were significantly lower in serum selenium than controls, and the estimated odds ratio of thyroid cancer increased from 1 for levels greater than or equal to 1.65 mumol/l, to 6.1 for levels 1.26-1.64 mumol/l, to 7.7 for levels less than or equal to 1.25 mumol/l. When time from blood sampling to diagnosis of the case was considered, it could be shown that the protective effect of high serum selenium concentrations was restricted to the last (less than 7) years prior to the diagnosis of thyroid cancer. The serum selenium concentration of cases tended to decrease relative to controls the shorter time was from blood sampling to the diagnosis. There was no difference between cases and controls with regard to serum copper.

Young suicide attempters: a comparison between a clinical and an epidemiological sample.

OBJECTIVE: To compare risk factors for self-harm in 2 groups: hospitalized adolescents who had attempted suicide and adolescents reporting suicide attempts in a community survey. METHOD: All suicide attempters aged 13 to 19 years admitted to medical wards (n = 91) in a region of Norway were assessed and interviewed. Risk factors were identified by comparisons with a general population sample participating in a questionnaire study in the same community (n = 1,736). In this population sample, a separate analysis of risk factors for reporting deliberate self-harm (n = 141) was performed, applying bivariate and multivariate logistic regression models. RESULTS: Adjusted risk factors for suicide attempts in hospitalized adolescents were depression (odds ratio [OR] = 4.7), disruptive disorders (OR = 9.4), low self-worth (OR = 1.3), infrequent support from parents (OR = 3.3) or peers (OR = 3.3), parents' excessive drinking (OR = 4.3), and low socioeconomic status (OR = 2.4). For adolescents who self-reported self-harm, depression (OR = 3.1) and loneliness (OR = 1.13) were significant adjusted risk factors (p < .001). Low self-worth, low socioeconomic status, and little support from parents or peers characterized hospitalized suicidal adolescents compared with those who were not hospitalized. CONCLUSIONS: The risk factors were more powerful for hospitalized than for nonhospitalized adolescents. Prevention efforts should target the same factors for both groups, at a population level for nonhospitalized adolescents and at an individual level for hospitalized adolescents, with a focus on depression, low self-esteem, and family communication.

Suicide among children and younger and older adolescents in Norway: a comparative study.

OBJECTIVE: To compare characteristics and risk factors of suicide in early adolescence (younger than age 15 years) and in late adolescence. The authors examined whether differences in risk factors or resilience might explain the different suicide rates in the two age groups. METHOD: Information about all registered suicides of young people in Norway from 1990 through 1992 was gathered from several professional informants. Children younger than 15 years old who committed suicide (n = 14) were compared with late-adolescent suicides (15 through 19 years) (n = 115) and with controls (n = 889). RESULTS: Younger compared with older adolescent suicides more often hanged themselves (93% versus 35%). Suicidal ideation (7% versus 39%) and precipitating events were described less frequently (29% versus 49%). Older adolescents more often had psychiatric disorders (77% versus 43%). Compared with controls, the risk factors for suicide were affective disorders (young adolescents: odds ratio [OR] = 23.8, 95% confidence interval [CI] = 2.3 to 1,183; older adolescents: OR = 19.6, CI = 10.6 to 38.8); disruptive disorders (young adolescents: OR = 3.4, CI = 0.0 to 340; older adolescents: OR = 6.1, CI = 3.0 to 12.7); and not living with two biological parents (young adolescents: OR = 3.1, CI = 0.6 to 14.7; older adolescents: OR = 2.5, CI = 1.6 to 3.8). CONCLUSION: Children and young adolescents completing suicide were less exposed to known risk factors than older adolescents. The increased suicide risk was similar for both groups when they were compared with community controls. The low suicide incidence in childhood may be related to fewer risk factors, rather than to resilience to risk factors.

Heavy drinking in the restaurant business: the role of social modelling and structural factors of the work-place.

The role of social modelling and structural factors of the work-place in predicting the probability of heavy drinking was investigated in a sample of 3267 Norwegian male and female waiters and cooks. In the logistic regression analysis, the probability of heavy drinking was increased by two social modelling factors and one structural factor. Having co-workers who, at least weekly, took an end-of-work drink at the work-place gave an odds ratio for heavy drinking of 2.8 (95% CI 1.9-4.1), and having co-workers who went out after work at least every week gave an odds ratio of 1.8 (95% CI 1.2-2.8). Working at a place with a liberal alcohol policy gave an odds ratio 1.5 (95% CI 1.1-2.2). Among the background factors, only household type significantly predicted heavy drinking. As compared with living with children, the odds for heavy drinking when living alone was 4.3 (95% CI 2.9-6.4). The results indicate that preventive measures in the restaurant business should not only concentrate on the individual, but also deal with factors related to the occupational activity that promote and sustain heavy drinking.

A cohort analysis of breast cancer, uterine corpus cancer, and childbearing pattern in Norwegian women.

STUDY OBJECTIVE: The aim was to study the influence of childbearing pattern on the incidence of breast cancer and uterine corpus cancer. DESIGN: This was an ecological study of birth cohorts of women. SETTING: The study was population based, involving the whole of Norway. PARTICIPANTS: The participants were Norwegian women born between 1890 and 1944. MEASUREMENTS AND MAIN RESULTS: Age specific fertility rates and age specific incidence rates for different birth cohorts were analysed by an age-cohort-period model where quantitative indices of the childbearing pattern substituted the cohort component. The 1890-94 birth cohort had the most favourable childbearing pattern with regard to the risk of breast cancer as well as uterine corpus cancer. The least favourable pattern was in the 1910-14 cohort for breast cancer and the 1940-44 cohort for uterine corpus cancer. In the analysis it is estimated that about 15% of the increase in incidence of breast cancer from 1955 to 1984 may be attributed to changes in the childbearing pattern of the cohorts under study. For cancer of the uterine corpus the corresponding fraction is about 27%. CONCLUSIONS: The study reveals that changes in childbearing pattern may explain a certain fraction of the observed increase in breast and uterine corpus cancer in Norway in the last 30 years, but the largest fraction must be accounted for by other factors.

No correlation in post-neonatal deaths for twins. A study of the early mortality of twins based on the Norwegian Medical Birth Registry.

The records of 10,204 pairs of twins born in Norway 1967-84 in the Norwegian Birth Registry were examined. The probabilities of stillbirth, neonatal death and post-neonatal death, conditional on the fate of the cotwin, were calculated. The neonatal death rate was four times increased when the cotwin was stillborn. When the cotwin died neonatally, the probability of postneonatal death was increased ninefold. The concordance rate for stillbirth and for neonatal death was above 0.4. In striking contrast, there was no correlation in postneonatal death for members of a twin pair. This finding suggests that genetic or common environmental factors play a minor role in the aetiology of post-neonatal death.

Cancer incidence among workers in six Norwegian aluminum plants.

OBJECTIVES: This study investigated associations between exposure to polycyclic aromatic hydrocarbons (PAH) and the incidence of lung, bladder, kidney, and pancreatic cancer among Norwegian aluminum plant workers. METHODS: Cancer incidence was investigated from 1953 to 1996 among 11,103 men employed for more than 3 years in the industry, giving 272,554 person-years during follow-up. A job exposure matrix was constructed to estimate exposure to particulate PAH and fluorides. The observed cases of cancer were compared with expected figures calculated from national rates. Dose-response relations were investigated by internal comparisons using Poisson regression and stratified analyses for standardized incidence ratio. Potential confounding by smoking was investigated in subanalyses restricted to 3 of the plants. RESULTS: The study showed an overall excess for bladder cancer, standardized incidence ratio 1.3 (95% confidence interval 1.1-1.5), which increased with increasing cumulative exposure to PAH and reached a relative risk of about 2 for the upper exposure category in the analysis with 30 years of lag time. There was no association between cumulative PAH exposure and lung cancer, but there were indications of an elevated risk of kidney cancer among the most heavily PAH-exposed persons in the analyses with a lag time of 30 years. For pancreatic cancer we found a higher incidence among the PAH-exposed persons than among the unexposed ones, but no clear dose-response association was found. CONCLUSIONS: The study showed an association between bladder cancer and exposure to PAH, but gave no support to an association between PAH exposure and lung cancer in the primary aluminum industry.

Nonmalignant mortality among workers in six Norwegian aluminum plants.

OBJECTIVES: This study investigated the associations between exposure to fluorides and polycyclic aromatic hydrocarbons (PAH) and mortality from nonmalignant diseases among workers in the Norwegian primary aluminum industry. METHODS: Mortality among 10,857 men, employed for more than 3 years in 1 of 6 aluminum plants, was investigated from 1962 to 1996, giving 239,246 person-years during follow-up. Ajob-exposure matrix covering all 6 plants was used to estimate the individual exposure to total fluorides and particulate PAH. The observed cause-specific deaths were compared with expected figures calculated from national rates. Dose-response relations were investigated by internal comparisons using Poisson regression and by stratified analyses for standardized mortality ratio. Potential confounding by smoking was investigated in subanalyses restricted to 3 of the plants for which information on smoking habits was accessible. RESULTS: Mortality from circulatory disease was slightly lower than expected [SMR 0.95, 95% confidence interval (95%CI) 0.9-1.0], while there was an increased mortality from asthma, emphysema, and chronic bronchitis combined, SMR 1.2 (95% CI 1.0-1.5). Mortality from these diseases was associated with cumulative exposure to fluorides. The rate ratio in the internal analysis rose steadily to 2.5 (95% CI 1.5-4.3) for the upper exposure category. No association was observed between cumulative fluoride exposure or PAH exposure and circulatory mortality. CONCLUSIONS: The study showed an association between exposure to potroom emissions measured by fluorides and mortality from asthma, emphysema, and chronic bronchitis combined.

Cancer incidence among Norwegian airline pilots.

OBJECTIVES: In this retrospective cohort study, the cancer incidence of commercial pilots was studied to determine whether exposure at work has any influence on the incidence of cancer. METHODS: The cohort was established from the files of the Civil Aviation Administration and included people who had valid licenses as commercial pilots between 1946 and 1994. Basic data about their flight careers were recorded, and exposure to cosmic radiation was estimated. The cohort was linked to the Cancer Register of Norway. The observed number of cases was compared with that expected based on national rates. RESULTS: A group of 3701 male pilots was followed over 70 560 person-years. There were 200 cases of cancer versus 188.8 expected, with a standardized incidence ratio (SIR) of 1.06 and a 95% confidence interval (95% CI) of 0.92-1.22. No significant decreased risk was found for any cancer site. Excess risks were found for malignant melanoma (22 cases SIR 1.8, 95% CI 1.1-2.7) and nonmelanoma skin cancer (14 cases, SIR 2.4, 95% CI 1.3-4.0). For malignant melanoma, there was a significant trend for the SIR by cumulative dose. CONCLUSIONS: For most cancer sites, the incidence among pilots did not deviate from that of the general population and could not be related to block hours of flight time or dose. It seems more likely that the excess risks of malignant melanoma and skin cancer are explained by factors related to life-style rather than by conditions at work.

Occupational exposure and cancer incidence among workers from an aluminum smelter in western Norway.

OBJECTIVES: This study investigated the associations between specific cancers and occupational exposure to polycyclic aromatic hydrocarbons (PAH), asbestos, electromagnetic fields, and heat in a cohort of workers from a Norwegian aluminum smelter. METHODS: Cancer incidence between 1953 and 1993 was observed for 2647 male short-term workers and 2 cohorts of men with at least 4 years' employment (2888 production workers and 373 maintenance workers). Standardized incidence ratios (SIR) were calculated from the national male cancer incidence, and associations with cumulative exposure were investigated by stratified analysis. Cumulative exposure in 15-year time windows was used as an alternative dose indicator. RESULTS: Investigation of the a priori hypotheses in the production cohort revealed a positive association between bladder cancer and PAH exposure 30 years or more before observation. The results also suggested an association between PAH and pancreatic cancer, although not statistically significant. No association was seen between exposure to PAH and cancers of the lungs or between magnetic field exposure and lymphatic and hematopoietic cancer. In the maintenance cohort there was a positive association between employment as an electrician and lymphatic and hematopoietic cancer and a statistically nonsignificant association between PAH and lung cancer. The short-term workers showed a statistically significant excess of lung cancer. CONCLUSIONS: The results support previous findings of an association between exposure to PAH and bladder cancer.

Youth suicide in Norway, 1990-1992: a comparison between children and adolescents completing suicide and age- and gender-matched controls.

In Norway 1990-1992, the suicide rate was 18.6 per 100,000 individuals per year for boys 15-19 years old and 6.3 for girls, and for 10-14 year olds the rate was 2.7 for boys and 0.5 for girls. Comparison of all completed suicides (N = 129) with gender- and age-matched control subjects identified depression (OR = 19.9; CI = 11.2, 35.5), disruptive disorders (OR = 6.0; CI = 3.1, 11.4), and previous suicidal behavior (OR = 3.4, CI = 2.0, 5.6) as main risk factors. Of the suicide completers, 74% had mental disorders. Suicidal intent was previously expressed by 48%, but few (24%) had received treatment, despite well-developed health services. A history of disruptive disorders (17%) and substance abuse (10%) were less frequently found than in previous studies, but binge drinking may contribute to the adolescent suicide rate.