Adenocarcinoma of the prostate in Iceland: a population-based study of stage, Gleason grade, treatment and long-term survival in males diagnosed between 1983 and 1987.

OBJECTIVE: To investigate adenocarcinoma of the prostate in a single population with an extended follow-up period. MATERIAL AND METHODS: Using the Icelandic Cancer Registry, we identified all Icelandic men diagnosed with prostate cancer between 1983 and 1987. Disease stage, initial treatment and follow-up information were obtained from hospital records and death certificates. A critical evaluation was made of the accuracy of the death certificates regarding prostate cancer. All available histology information was reviewed and graded according to the Gleason grading system. RESULTS: A total of 414 men were diagnosed with adenocarcinoma of the prostate. Of these, 370 were alive at the time of diagnosis and stage could be determined. Four stage groups were defined: focal incidental (n=50); localized (n=164); local advanced (n=32); and metastatic disease (n=124). The mean age at diagnosis was 74.4 years (range 53-94 years). The combined Gleason score was 2-5 in 89, 6-7 in 117, 8-10 in 117 and unknown in 47 cases. The median follow-up period for the group was 6.15 years (range 0.3-19.8 years). Thirty men received treatment with curative intent: radiation therapy, n=20; and radical prostatectomy, n=10. A total of 334 patients died during the follow-up period, of whom 168 (50%) died of prostate cancer. Prostate cancer-specific survival at 10 and 15 years was 100% and 90.6%, respectively for focal incidental cancer; 73.1% and 60.8% for men with localized disease; 23.4% and 11.7% for local advanced disease; and 6.81% and 5.45% for metastatic disease. A Cox multivariate analysis showed age, stage and Gleason score to be independent predictors of prostate cancer death. A total of 104 patients with localized disease and a Gleason score of

Cosmic radiation and cancer mortality among airline pilots: results from a European cohort study (ESCAPE).

Cosmic radiation is an occupational risk factor for commercial aircrews. In this large European cohort study (ESCAPE) its association with cancer mortality was investigated on the basis of individual effective dose estimates for 19,184 male pilots. Mean annual doses were in the range of 2-5 mSv and cumulative lifetime doses did not exceed 80 mSv. All-cause and all-cancer mortality was low for all exposure categories. A significant negative risk trend for all-cause mortality was seen with increasing dose. Neither external and internal comparisons nor nested case-control analyses showed any substantially increased risks for cancer mortality due to ionizing radiation. However, the number of deaths for specific types of cancer was low and the confidence intervals of the risk estimates were rather wide. Difficulties in interpreting mortality risk estimates for time-dependent exposures are discussed.

Breast cancer risk in airline cabin attendants: a nested case-control study in Iceland.

AIMS: To investigate whether length of employment as a cabin attendant was related to breast cancer risk, when adjusted for reproductive factors. METHODS: Age matched case-control study nested in a cohort of cabin attendants. The cases were found from a nationwide cancer registry (followed up to end of year 2000) and the reproductive factors (age at first childbirth and number of children) from a registry of childbirth, in both instances by record linkage with the cabin attendants' identification numbers. The employment time of the cabin attendants at the airline companies and the reproductive factors had been systematically recorded prior to the diagnosis of breast cancer in the cohort. A total of 35 breast cancer cases and 140 age matched controls selected from a cohort of 1532 female cabin attendants were included in the study. RESULTS: The matched odds ratio from conditional logistic regression of breast cancer risk among cases and controls of cabin attendants was 5.24 (95% CI 1.58 to 17.38) for those who had five or more years of employment before 1971 compared with those with less than five years of employment before 1971, adjusted for age at first childbirth and length of employment from 1971 or later. CONCLUSIONS: The association between length of employment and risk of breast cancer, adjusted for reproductive factors, indicates that occupational factors may be an important cause of breast cancer among cabin attendants; the association is compatible with a long induction period.

Risk factors for cutaneous malignant melanoma among aircrews and a random sample of the population.

AIMS: To evaluate whether a difference in the prevalence of risk factors for malignant melanoma in a random sample of the population and among pilots and cabin attendants could explain the increased incidence of malignant melanoma which had been found in previous studies of aircrews. METHODS: A questionnaire was used to collect information on hair colour, eye colour, freckles, number of naevi, family history of skin cancer and naevi, skin type, history of sunburn, sunbed, all sunscreen use, and number of sunny vacations. RESULTS: The 239 pilots were all males and there were 856 female cabin attendants, which were compared with 454 males and 1464 females of the same age drawn randomly from the general population. The difference in constitutional and behavioural risk factors for malignant melanoma between the aircrews and the population sample was not substantial. The aircrews had more often used sunscreen and had taken more sunny vacations than the other men and women. The predictive values for use of sunscreen were 0.88 for pilots and 0.85 for cabin attendants and the predictive values for sunny vacation were 1.36 and 1.34 respectively. CONCLUSION: There was no substantial difference between the aircrew and the random sample of the population with respect to prevalence of risk factors for malignant melanoma. Thus it is unlikely that the increased incidence of malignant melanoma found in previous studies of pilots and cabin attendants can be solely explained by excessive sun exposure.

Acute Q fever: a cause of fatal hepatitis in an Icelandic traveller.

Domestic Q fever is rare in the Nordic countries; the infection is acquired abroad in the majority of cases. This is the first Nordic report of a fatal case of Q fever, which occurred in an Icelandic cancer patient who had travelled to the Canary Islands.

Risk of breast cancer in female flight attendants: a population-based study (Iceland).

OBJECTIVES: To study whether increased cancer risk, particularly of cancer types previously related to radiation, was found among cabin attendants, using employment time as a surrogate of exposure to cosmic radiation. METHODS: A cohort of 1690 cabin attendants, 158 men and 1532 women from the Icelandic Cabin Crew Association and two airline companies in Iceland, was established. Cancer sites were ascertained between 1955 and 1997 by follow-up in a cancer registry. The personal identification number of each subject was used in record linkage to population-based registers containing vital and emigration status, reproductive factors and histologically verified cancer diagnosis. Standardized incidence rates (SIR) of different cancer sites in relation to employment time and year of hiring were calculated, as well as predictive values of breast cancer risk for evaluating possible confounding due to reproductive factors. RESULTS: The total number of person-years was 27,148. Among the women, 64 cancers were observed whereas 51.63 were expected (SIR 1.2, 95% CI 1.0-1.6), and significantly increased risk for malignant melanoma (SIR 3.0, 95% CI 1.2-6.2) was found. Significantly increased risks of overall cancers (SIR 1.3, 95% CI 1.0-1.8) and breast cancer (SIR 1.6, 95% CI 1.0-2.4) were observed among the female cabin attendants when 15 years lag time was applied. Those hired in 1971 or later had the heaviest exposure to cosmic radiation at a young age and had significantly increased risk of overall cancer (SIR 2.8, 95% CI 1.4-4.9) and breast cancer (SIR 4.1, 95% CI 1.7-8.5). Predictive values calculated on the basis of reproductive factors among the cabin attendants and the population, and risk of breast cancer were 1.0 for parous vs. nulliparous, 1.0 for number of children, and 1.1 for age at birth of first child. CONCLUSION: The increased risk of breast cancer and malignant melanoma among cabin attendants seems to be occupationally related. The part played by occupational exposures, i.e. cosmic radiation, disturbance of the circadian rhythm, and electromagnetic fields or combination of these factors in the etiology of breast cancer among the cabin crew, is still a puzzle as confounding due to parity appears to be ruled out. The relationship between the sunbathing habits of the cabin crew and the increased risk of malignant melanoma needs to be clarified. There is also an urgent need to elucidate the importance of these findings for today's aviation.

Incidence of cancer among commercial airline pilots.

OBJECTIVES: To describe the cancer pattern in a cohort of commercial pilots by follow up through the Icelandic Cancer Registry. METHODS: This is a retrospective cohort study of 458 pilots with emphasis on subcohort working for an airline operating on international routes. A computerised file of the cohort was record linked to the Cancer Registry by making use of personal identification numbers. Expected numbers of cancer cases were calculated on the basis of number of person-years and incidences of cancer at specific sites for men provided by the Cancer Registry. Numbers of separate analyses were made according to different exposure variables. RESULTS: The standardised incidence ratio (SIR) for all cancers was 0.97 (95% confidence interval (95% CI) 0.62 to 1.46) in the total cohort and 1.16 (95% CI 0.70 to 1.81) among those operating on international routes. The SIR for malignant melanoma of the skin was 10.20, 95% CI 3.29 to 23.81 in the total cohort and 15.63, 95% CI 5.04 to 36.46 in the restricted cohort. Analyses according to number of block-hours and radiation dose showed that malignant melanomas were found in the subgroups with highest exposure estimates, the SIRs were 13.04 and 28.57 respectively. The SIR was 25.00 for malignant melanoma among those who had been flying over five time zones. CONCLUSIONS: The study shows a high occurrence of malignant melanoma among pilots. It is open to discussion what role exposure of cosmic radiation, numbers of block-hours flown, or lifestyle factors--such as possible excessive sunbathing--play in the aetiology of cancer among pilots. This calls for further and more powerful studies. The excess of malignant melanoma among those flying over five time zones suggests that the importance of disturbance of the circadian rhythm should be taken into consideration in future studies.

Serum thyroglobulin as a risk factor for thyroid carcinoma.

Samples from a biological serum bank taken up to 23 years prior to diagnosis of thyroid carcinoma were analysed for human thyroglobulin, thyroid-stimulating hormone and thyroxin. After exclusions, the final study material consisted of 59 cases of papillary and follicular carcinomas. These cases were compared with 164 controls, matched for sex, age and time of sample taking. The most interesting finding was that concentrations of thyroglobulin in serum were abnormally elevated in cases compared with controls, equal to or above 30 microg/L, with odds ratio 7.0 (CI 3.1-15.7). This elevation of serum thyroglobulin occurred in 44% of the carcinoma cases. Sensitivity was around 50 for measurements taken up to 15 years prior to diagnosis, but 21 when the interval was over 15 years. Specificity was 89. No differences were found between cases and controls in values for thyroid-stimulating hormone and thyroxin.

Nuclear DNA analysis and prognosis in carcinoma of the thyroid gland. A nationwide study in Iceland on carcinomas diagnosed 1955-1990.

The purpose of this study was to ascertain whether DNA ploidy status and S-phase fraction affected the prognosis of patients with carcinoma of the thyroid gland. We reviewed all malignant thyroid tumours diagnosed in Iceland from 1955 to 1990. In all, 494 thyroid carcinomas were diagnosed during that period. By analysing tumour material from paraffin blocks by flow cytometry we were able to evaluate the ploidy status in 424 tumours and the S-phase value in 417 tumours. We detected aneuploid cell populations in 9.7% of papillary carcinomas, 24.3% of follicular carcinomas, 42.9% of medullary carcinomas and 78.6% of anaplastic carcinomas. Some 57% of tumours, mainly papillary carcinomas, had an S-phase value of less then 3%, whereas most of the other histological types of carcinoma, including all the anaplastic tumours, had an S-phase value of > or = 3%. Univariate analysis indicated that both ploidy status and S-phase fraction were significant variables. When taking into account known prognostic variables of thyroid carcinoma in a multivariate analysis, however, neither ploidy status nor S-phase value proved significant. We conclude that DNA ploidy status and S-phase values are not independent prognostic factors in thyroid carcinoma.

[Thyroid cancer in Iceland. Epidemiology and prognostic factors with special emphasis on the results of nuclear DNA-analysis].

All malignant primary tumours of the thyroid gland in Iceland during the 36 years 1955 to 1990 were studied. In all 494 thyroid carcinomas were diagnosed during that period. A considerable increase in the reported incidence of thyroid cancer was noted around 1965 and a decline around 1980. These changes are mainly due to variability in incidence of papillary carcinomas in females. The survival rate corrected for intercurrent death was similar for both papillary and follicular carcinomas. During the observation period there was a decline in mortality rate for this disease. In this study we also analysed if DNA-ploidy status and S-phase fraction had an effect on the prognosis of patients with carcinoma of the thyroid gland. By analysing tumour material from paraffin blocks we were able to evaluate the ploidy status in 424 tumours and S-phase value in 417 tumours. Univariate analysis showed that both the ploidy status and the S-phase fraction gave significant values. When taking into account known prognostic variables of thyroid carcinoma in a multivariate analysis neither the ploidy status nor the S-phase value proved significant.

Tumours in Iceland. 17. Malignant tumours of the oesophagus. Histological classification and epidemiological considerations.

We studied all primary malignancies of the oesophagus diagnosed in Iceland between 1955 and 1984 and reclassified tumours where histological material was available using the WHO classification system. Of a total of 329 tumours diagnosed in the time period, seven were excluded for various reasons. Of the remaining 322 tumours, 178 were in males and 144 in females. The age standardized incidence was 5.3/10(5) for males and 3.1/10(5) for females. The incidence of oesophageal tumours decreased for both sexes during the time period under investigation. Of 250 reclassified tumours (142 in males and 108 in females), squamous cell carcinomas comprised 81.6%. If the undifferentiated tumours are excluded, the squamous group accounted for 89.1% of the remaining tumours. Small cell carcinomas comprised 3.2% of all cases, which was higher than expected. Most of the tumours appear to be located in the middle part of the oesophagus. The vast majority of resected tumours extended through the wall of the oesophagus. A relatively higher proportion of tumours was confined to the submucosal or muscular layers in the latter half of the period. In conclusion, the epidemiological data in our study appear to resemble what is observed in the other Nordic countries for oesophageal tumours, except for slightly higher overall incidence in Iceland, especially for women.

Screening as a prognostic factor in cervical cancer: analysis of survival and prognostic factors based on Icelandic population data, 1964-1988.

Survival rates were computed for 376 women diagnosed with carcinoma of the uterine cervix between 1964 and 1988. The 5-year survival rate for the entire group was 63%. The effect of age at diagnosis, clinical stage, histopathology, year of diagnosis, and screening program attendance was studied by univariate analysis and simultaneously with a multivariate analysis, the Cox proportional hazards model. All these parameters had a significant effect on survival, with clinical stage as the strongest parameter followed by histology, year of diagnosis, age at diagnosis, and attendance at screening. Women who had attended the cervical screening program fared significantly better than those who had never attended. Patients treated in the late years of the study period had a significantly better survival rate, possibly indicating improved treatment. Young women had a significantly better prognosis than older women. Women with adenocarcinoma and anaplastic tumors had a significantly worse prognosis than women with squamous and adenosquamous carcinoma. The prognostic effect of screening was mainly attributed to the more favorable distribution of early stages and younger age at diagnosis among the screened women. After all the analyzed parameters had been adjusted for the nonattenders still had poorer prognosis.

Tumours in Iceland. 14. Malignant tumours of soft tissues. Histological classification and epidemiological considerations.

All malignant tumours of soft tissues diagnosed in Iceland between 1955 and 1988 were reviewed histologically. Of a total of 155 tumours, 129 were, on review, soft tissue sarcomas, while 26 had been erroneously diagnosed and were excluded from the study. In 25% of the tumours the original sarcoma diagnosis was changed to another sarcoma type. Malignant fibrous histiocytoma, liposarcoma and leiomyosarcoma together comprise more than half of all tumours diagnosed. Contrary to previous estimations, according to this study, the age-standardized incidence of soft tissue sarcoma in Iceland is 1.8 per 1000,000 for males and 1.6 per 100,000 per females, which is similar to incidence rates in the other Nordic countries. The majority of sarcomas were of relatively high grade. The tumours were graded using both three and four grades of malignancy. Both systems yielded prognostic information although it was not possible to detect significant differences in survival for grade I and grade II tumours when the four grade system was used. The results of this study show that the epidemiology of soft tissue sarcoma in Iceland is similar to that found in other Western countries.

Soft tissue sarcomas in Iceland 1955-1988. Analysis of survival and prognostic factors.

From 1955 to 1988 a total of 129 cases (69 males and 60 females) of soft tissue sarcomas were diagnosed in Iceland, four at autopsy. The median age was 55 years (0-91). All the cases have been reviewed clinically and histopathologically and graded on both a three- and a four-point scale. The average age-standardized incidence was 1.8/100,000 for males and 1.6 for females. The tumour was most often localized in the thigh and retroperitoneal space. The most common histologic subtypes were malignant fibrous histiocytoma (22.5%), liposarcoma (18.6%) and leiomyosarcoma (16.3%). The 5- and 10-year survival rates (n = 125) were 38% and 29% respectively. Cox's multivariate analysis was performed on the following prognostic factors: age, sex, tumour localization, histopathologic subtype, tumour size, malignancy grade and year of diagnosis. The strongest prognostic factor was malignancy grade (IV vs I; p less than 0.001 and RR = 5.35 and III vs I; p = 0.017 and RR = 2.01) followed by tumour size (pT2 vs pT1; p less than 0.001 and RR = 3.09 and pT3 vs pT1; p = 0.002 and RR = 3.40) and year of diagnosis (p = 0.003 and RR = 0.96; corresponding to a 54% reduction in mortality risk during a 20-year period).

Reproductive factors and breast cancer risk in Iceland. A second cohort study.

In a previous prospective study we showed elevated risks for breast cancer in nulliparous women compared to parous women, in those having their first pregnancy at a higher age, and those with few children. This was based on 216 women diagnosed with breast cancer during 1965 to 1975 among 34,525 women having attended the cervix cancer detection clinic in Iceland by the end of 1974, and born between 1906 and 1945. The present investigation on 848 cases, diagnosed among 61,040 women attending the cervix cancer detection clinic during 1964 to 1984 and born between 1901 and 1960, shows the same risk factors to be significant. The relative risks are, however, smaller. The reasons for the difference in relative risks are discussed. We find that the effect of age at first birth is significant for women up to the age of 65 and not for older women. In both cohorts, women older than 55 are underrepresented and more so in the earlier report. In addition, the small number of cases in the reference group with age at first birth below 20 appears to have made the figures of our earlier report unreliable.

Tumours in Iceland. 11. Malignant tumours of the thyroid gland. A histological classification and epidemiological considerations.

All malignant primary tumours of the thyroid gland submitted for histological diagnosis in Iceland during the 30 years 1955-1984, and available for review, were typed histologically according to the World Health Organization classification but also taking into account the more recent well recognized follicular variant of papillary carcinoma. A total of 480 thyroid tumours were classified with a female--to male ratio of 2.8 (367 females, 129 males). The age distribution is much what would be expected, the anaplastic type of carcinomas occurring in the elderly while papillary and follicular tumours occur over a much wider age range. The incidence of thyroid carcinomas in Iceland is about 2-3 times higher than in the other Nordic countries. This is largely due to an unusually high incidence of the papillary type of carcinoma. Overall, the papillary carcinoma accounted for 80% of thyroid malignancies. The tumours diagnosed incidentally at autopsy were about 20% of the entire material, and these tumours were only of the differentiated types of thyroid carcinoma. Even if the incidentally diagnosed tumours are excluded, the percentage of papillary tumours is 77% which is unusually high. The papillary type of carcinomas occasionally occurred in familial clusters in Iceland but not sufficiently to account for the unusually high incidence. Some of the possible etiological factors are discussed.

Papillary thyroid carcinoma in Iceland. A study of the occurrence in families and the coexistence of other primary tumours.

This paper presents evidence from Iceland which indicates that papillary thyroid carcinoma occurs in certain families more often than expected. Thyroid carcinoma was also seen to coexist with some other cancer types more often than expected. We studied all families (n = 373) with papillary thyroid carcinoma diagnosed between 1955 and 1984 in Iceland. Familial papillary carcinoma occurred in 3.8% of these families. This frequency was higher than expected but not significantly increased. Second primaries in women, and especially the incidence of kidney and breast cancer, were significantly increased. Cancer of the kidney and CNS tumours were significantly increased in propositi when both sexes were taken together. No increase in the incidence of other malignancies was observed in first degree relatives of patients with papillary thyroid carcinoma.

Thyroid cancer in Iceland 1955-1984.

A retrospective study was carried out on the incidence of thyroid cancer in Iceland from 1955 to 1984. During this 30-year period 406 cases of thyroid cancer were registered. The incidence of 9.5 for females and 3.4 for males per 100,000 per year is at least twice as high as in the other Nordic countries and among the highest incidence figures reported anywhere. A considerable increase in the reported incidence of thyroid cancer was noted around 1965. The mean size of the cancer nodules at diagnosis decreased at the same time and survival rates of patients improved. The incidence decreased again during the last 5 years of the study period. Mortality rates remained similar during this 30-year period. The survival rate corrected for intercurrent death was similar for both papillary and follicular carcinomas. All patients with anaplastic carcinomas died within one year of diagnosis. Cox's regression analysis with multiple covariates revealed that age at diagnosis, anaplastic and medullary history type as compared with papillary type, pathological evaluation of tumour extent, and calendar period of diagnosis had significant prognostic power. Sex and follicular vs papillary histology type were not significant prognostic factors.

A comparative study of DNA cytometry methods for benign and malignant thyroid tissue.

DNA measurements of 46 thyroid specimens were performed by use of fresh tissue for flow cytometry and formalin-fixed paraffin-embedded tissue for flow and static cytometry. The tissue included four histopathologic subgroups, i.e., 19 colloid goiters, 7 papillary carcinomas, 10 follicular adenomas, and 10 follicular carcinomas. The methods measured DNA index and the percentage of cells in S-phase for each subgroup. There was a strong correlation between the methods for DNA-index measurements. In three cases, tissue interpreted as diploid by one method was aneuploid by another method. The S-phase measurements were not reproducible between the methods because of the low percentage of cells in S-phase (mean: 2.6%; range: 0.0-7.5% overall). Aneuploid cells were rare in nodular goiter (2 of 19 cases, 10.5%) but were increasingly present in subsequent subgroups, i.e., 2 of 7 papillary carcinomas (28%), 3 of 10 follicular adenomas (30%), and 6 of 10 follicular carcinomas (60%).