Pentti Kyyrönen

Spontaneous abortions and malformations in the offspring of nurses exposed to anaesthetic gases, cytostatic drugs, and other potential hazards in hospitals, based on registered information of outcome.

Nurses working in selected departments of general hospitals in Finland were collected from a central register on health personnel in Finland. Using the Hospital Discharge Register and the Register of Congenital Malformations, case nurses were selected who had had a spontaneous abortion (N = 217) or a malformed child (N = 46) between the years 1973 and 1979. Controls consisted of three nurses who had had a normal birth; the control nurses were matched for age and hospital of employment. Information on exposure in the first trimester of pregnancy was sought through the head nurses of the hospitals. No significant increase in risk of spontaneous abortion or of malformation was observed after exposure to anaesthetic gases (odds ratio for spontaneous abortion 1.2), sterilising gases and soaps, or x-rays. Handling of cytostatic drugs did not affect the frequency of spontaneous abortion but was associated with malformations in the offspring. The odds ratio, based on eight cases, was 4.7 (p = 0.02) when the logistic model was adopted. The results suggest that the exposures investigated, other than cytostatic drugs, do not cause a strong reproductive risk. Further studies are needed, particularly on cytostatic drugs.

Laboratory work and pregnancy outcome.

Spontaneous abortions among women working in laboratories, and congenital malformations and birth weights of the children were examined in a retrospective case-referent study. In the spontaneous abortion study there were 535 women (206 cases and 329 referents), and in the malformation study 141 women (36 cases and 105 referents). The analysis of the birth weights concerned 500 women (referents). Significant associations with spontaneous abortion were found for exposure to toluene (odds ratio [OR], 4.7, 95% confidence interval [CI], 1.4 to 15.9), xylene (OR 3.1, CI 1.3 to 7.5) and formalin (OR 3.5, CI 1.1 to 11.2) > or = 3 days a week, adjusted for the covariates. Most of the women exposed to formalin and xylene were working in pathology or histology laboratories. No association with congenital malformation was found.

Incidence of cancer among Nordic airline pilots over five decades: occupational cohort study

Abstract Objective: To assess the incidence of cancer among male airline pilots in the Nordic countries, with special reference to risk related to cosmic radiation. Design: Retrospective cohort study, with follow up of cancer incidence through the national cancer registries. Setting: Denmark, Finland, Iceland, Norway, and Sweden. Participants: 10 032 male airline pilots, with an average follow up of 17 years. Main outcome measures: Standardised incidence ratios, with expected numbers based on national cancer incidence rates; dose-response analysis using Poisson regression. Results: 466 cases of cancer were diagnosed compared with 456 expected. The only significantly increased standardised incidence ratios were for skin cancer: melanoma 2.3 (95% confidence interval 1.7 to 3.0), non-melanoma 2.1 (1.7 to 2.8), basal cell carcinoma 2.5 (1.9 to 3.2). The relative risk of skin cancers increased with the estimated radiation dose. The relative risk of prostate cancer increased with increasing number of flight hours in long distance aircraft. Conclusions: This study does not indicate a marked increase in cancer risk attributable to cosmic radiation, although some influence of cosmic radiation on skin cancer cannot be entirely excluded. The suggestion of an association between number of long distance flights (possibly related to circadian hormonal disturbances) and prostate cancer needs to be confirmed.

Night-time work predisposes to non-Hodgkin lymphoma.

Our aim was to find out whether non‐Hodgkin lymphoma (NHL) was more common than expected among night‐time shift workers. The Finnish job‐exposure matrix (FINJEM) provided estimates of the proportion of exposed persons and the mean level of exposure among the exposed in each occupation. The probability of night‐time work in each occupation was assessed, the observed and expected numbers of cancer cases in a cohort of persons born in 1906–1945 during the years of 1971–1995 were calculated, and the cumulative index of night‐time work was scored. The cohort compromised of 1,669,272 persons of whom 6,307 (3,813 men and 2,494 women) had NHL during the follow‐up. Night‐time work increased significantly (p = 0.01) the risk of NHL in men, the overall relative risk being 1.10 (95% confidence interval of 1.03–1.19). Using the lag period of 10 years, the risk ratio was 1.28 (1.03–1.59) for men who worked in night‐time shifts to a high degree as compared with those who had not been exposed to night‐time work. Night‐time workers are cancer prone and have a greater risk of NHL than population on average.

Nordic biological specimen banks as basis for studies of cancer causes and control - More than 2 million sample donors, 25 million person years and 100 000 prospective cancers

The Nordic countries have a long tradition of large-scale biobanking and comprehensive, population-based health data registries linkable on unique personal identifiers, enabling follow-up studies spanning many decades. Joint Nordic biobank-based studies provide unique opportunities for longitudinal molecular epidemiological research. The purpose of the present paper is to describe the possibilities for such joint studies, by describing some of the major Nordic biobank cohorts with a standardised calculation of the cancer incidence in these cohorts. Altogether two million donors have since 1966 donated more than four million biological samples, stored at −20°C to −135°C, to 17 biobank cohorts in Finland, Iceland, Norway and Sweden. As a result of joint database handling principles, the accuracy of personal identifiers and completeness of follow-up for vital status in all participating biobanks was improved. Thereafter, the cancer incidence was determined using follow-up through the national cancer registries. Biobanks based on random samples of population typically showed slightly lower cancer incidence rates than the general population, presumably due to better participation rates among health-conscious subjects. On the other hand, biobanks including samples for viral screening or clinical testing showed 1.5 to 2.1 fold increased incidence of cancer. This excess was very high immediately after sampling, but for some cancer sites remained elevated for years after clinical sampling. So far, more than 100 000 malignant neoplasms have occurred after sample donation, and the annual increase of the cancer cases in these cohorts is about 10 000. The estimates on the population-representativity of the biobanks will assist in interpretation of generalizability of results of future studies based on these samples, and the systematic tabulations of numbers of cancer cases will serve in study power estimations. The present paper summarizes optimal study designs of biobank-based studies of cancer.

Breast cancer in Belarus and Ukraine after the Chernobyl accident

An increase in breast cancer incidence has been reported in areas of Belarus and Ukraine contaminated by the Chernobyl accident and has become an issue of public concern. The authors carried out an ecological epidemiological study to describe the spatial and temporal trends in breast cancer incidence in the most contaminated regions of Belarus and Ukraine, and to evaluate whether increases seen since 1986 correlate to radiation exposure from the Chernobyl accident. The authors investigated the trends through age‐cohort‐period‐region analyses of district‐specific incidence rates of breast cancer for Gomel and Mogilev regions of Belarus and Chernigiv, Kyiv and Zhytomir regions of Ukraine. Dose‐response analyses were based on Poisson regression, using average district‐specific whole body doses accumulated since the accident from external exposure and ingestion of long‐lived radionuclides. The study demonstrated increases in breast cancer incidence in all areas following the Chernobyl accident, reflecting improvements in cancer diagnosis and registration. In addition, a significant 2‐fold increase in risk was observed, during the period 1997–2001, in the most contaminated districts (average cumulative dose of 40.0 mSv or more) compared with the least contaminated districts (relative risk [RR] in Belarus 2.24, 95% confidence interval [CI] 1.51–3.32 and in Ukraine 1.78, 95% CI = 1.08–2.93). The increase, though based on a relatively small number of cases, appeared approximately 10 years after the accident, was highest among women who were younger at the time of exposure and was observed for both localised and metastatic diseases. It is unlikely that this excess could be entirely due to the increased diagnostic activity in these areas.

Scholastic Achievements of Childhood Leukemia Patients: A Nationwide, Register-Based Study

PURPOSEnStudies concerning the scholastic achievement of survivors of childhood leukemia have yielded controversial results. We studied the school marks of childhood leukemia survivors in a register-based study.nnnPATIENTS AND METHODSnThree hundred seventy-one patients with a diagnosis of leukemia before the age of 16 years who were born between 1974 and 1986 and alive on their 16th birthday were identified from the Finnish Cancer Registry. Five matched controls were sought for each patient from the Population Register Center of Finland. Information on the ninth-grade school report was obtained from Statistics Finland. The overall mark average and the marks (scale 4 to 10) for mother tongue, foreign language, mathematics, and physical education were compared between the patients and controls.nnnRESULTSnThe ninth-grade school report was obtained by 97.6% of the patients and 98.5% of the controls. The patients whose treatment included cranial irradiation had a lower overall mark average (mean difference, -0.24; 95% CI, -0.33 to -0.15) and lower marks for all assessed school subjects compared with their controls. Of the patients treated with chemotherapy alone, only the females with leukemia diagnosed before 7 years of age had lower school marks than their controls. The biggest difference was observed in the marks for foreign language among the irradiated females diagnosed at a young age (mean difference, -1.0; 95% CI, -1.25 to -0.74).nnnCONCLUSIONnLeukemia treatment that includes cranial irradiation impairs scholastic achievement. It is noteworthy that treatment of leukemia with chemotherapy alone impairs school performance only in females diagnosed before school age.

Spontaneous abortions and congenital malformations among women exposed to tetrachloroethylene in dry cleaning.

STUDY OBJECTIVE: The aim of the study was to determine whether exposure to tetrachloroethylene during the first trimester of pregnancy has harmful effects on pregnancy outcome. DESIGN: The study used record linkage identification of cases and case-control comparison. SETTING: The study involved dry cleaner and laundry workers throughout Finland who had become pregnant during the study period. Controls were age matched but otherwise unselected women giving birth to normal babies in the study period. SUBJECTS: Cases were defined as women who had been treated for spontaneous abortion or had delivered a malformed child. Out of 5700 workers nearly half had been pregnant during the study period. One pregnancy only was randomly selected for study per worker, and the final study population was 247 women with spontaneous abortions and 33 with malformed infants. Three age matched controls were selected for each abortion case and five for each malformation case. MEASUREMENTS AND MAIN RESULTS: Three women out of four had worked in early pregnancy. Exposure information was collected from 1108 women by mailed questionnaires, with a 77% response, and was partly confirmed by biological monitoring data. Exposure to tetrachloroethylene was found to be significantly associated with spontaneous abortions (odds ratio 3.6, p less than 0.05). CONCLUSION: The findings, together with other available data, indicate that exposure of pregnant women to tetrachloroethylene needs to be minimised.

Survival of breast cancer patients in BRCA1, BRCA2, and non‐BRCA1/2 breast cancer families: A relative survival analysis from Finland

Reports on the prognosis of familial breast cancer patients have been contradictory. True differences in survival, if they exist, would have important implications for genetic counselling and in treatment of hereditary breast cancer. We assessed the survival rates of 359 familial breast cancer patients (32 patients from BRCA1‐positive families, 43 patients from BRCA2‐positive families and 284 patients from BRCA1/2‐negative breast cancer families) and compared them with those of all other breast cancer patients diagnosed in Finland from 1953 to 1995 (n = 59,517). Cumulative relative survival rates (RSR) were calculated by dividing the observed survival rates by the expected ones. The expected survival rates were derived from the sex, age and calendar year specific life‐tables of the general population in Finland. Regression model was used to calculate relative excess risk of death (RR) and to adjust for confounding factors. The overall 5‐year RSR of the patients in the BRCA1 families, BRCA2 families, non‐BRCA1/2 families and among sporadic cases was 67%, 77%, 86% and 78%, respectively. However, we found no significant differences in the RR adjusted for age, stage and year of diagnosis between the different familial patient groups or the general breast cancer population. In the BRCA1 families the RR tended to be higher [RR 1.30, 95% confidence interval (CI) 0.63–2.70] and in the BRCA2 families lower (RR 0.78, 95% CI 0.39–1.57) than among the general breast cancer patient population. The RR among patients in the non‐BRCA1/2 families did not differ from that of the general patient population.

Reduced Fertility Among Female Wood Workers Exposed to Formaldehyde

BACKGROUNDnThe aim of the study was to investigate whether exposure to formaldehyde, organic solvents or other chemicals in the wood-processing industry affects the fertility of women.nnnMETHODSnFor this purpose, a retrospective study on time to pregnancy was conducted among female wood workers who had given birth during 1985-1995. Data on pregnancy history, time to pregnancy, occupational exposures, and potential confounders were collected by a questionnaire; 64% (699/1,094) participated. The exposure assessment was conducted by an occupational hygienist. The data on time to pregnancy were analyzed with the discrete proportional hazards regression.nnnRESULTSnExposure to formaldehyde was significantly associated with delayed conception: adjusted fecundability density ratio, FDR, was 0.64 (95% CI 0.43-0.92). At high exposure if no gloves were used, the FDR was 0.51 (% CI 0.28-0.92). Exposure to phenols, dusts, wood dusts, or organic solvents was not related to the time to pregnancy. Additionally, an association was observed between exposure to formaldehyde and an increased risk of spontaneous abortion (concerning previous spontaneous abortions, reported by the women). Associations between exposure to formaldehyde or to organic solvents and endometriosis, and between exposure to organic solvents or to dusts and salpingo-oophoritis were also suggested.nnnCONCLUSIONSnThe study suggests that a womans occupational exposure to formaldehyde has an adverse effect on fertility.