Cancer incidence in 13811 patients skin tested for allergy.

AIM: Several studies have shown a negative correlation between cancer and atopy-related diseases. There are also a few reports of a positive relationship. We wanted to further evaluate these relationships in a prospective study. SUBJECTS AND METHODS: The incidence of malignant diseases among adult patients with atopy-related diseases (asthma, rhinitis, urticaria, eczema etc; n = 13811), who had been skin prick tested in 1976-1999 was compared with the incidence in the general population. Expected cancer incidence from the date of skin prick testing up to 1999 was obtained from cause-, sex-, calendar-year-, and 5-year-age-group specific incidence rates for the county. These rates were calculated from cancer incidence and population counts obtained from the Swedish Cancer Register. The 95% confidence intervals (CIs) for cause-specific standardized incidence ratios (SIRs) were calculated. Skin prick tests were performed with Dermatophagoides pteronyssinus, horse, dog, cat, timothy, mugwort, birch, and Cladosporium. Patients having one or several positive skin prick test reactions (> or = 2+) were regarded as atopics. RESULTS: 119 cases of cancer occurred among 6224 atopic individuals (SIR 1.0) compared with 216 cases (SIR 0.94, CI 0.82-1.08) among 6358 non-atopics. There was a slight excess of Hodgkin's lymphoma cases among atopic men (SIR 4.03, 95% CI 1-10.3), and of non Hodgkin lymphoma cases among atopic women (SIR 4.52, 95% CI 1.23-11.6). However, a large number of comparisons were made which can have caused random findings. CONCLUSIONS: The results showed no associations between atopy or allergic symptoms, and subsequent cancer risk, but supported the theory that type-I allergy is not related to cancer risk.

Cancer incidence in the Swedish leather tanning industry: updated findings 1958-99.

AIMS: To assess how a 10 year extension of the follow up period affected cancer incidence in the Swedish leather tanning cohort. METHODS: A cohort of 2027 tannery workers (of which 482 were women) who had been employed for at least one year between 1900 and 1989 at one of three Swedish leather tanneries, was established. The start of observation varied between 1958 and 1966 for the three plants. Through linkage with the Swedish Cancer Registry, incident cancer cases were recorded up to 1999. Cause specific expected cancer incidence was calculated for 1958-99 based on calendar year, sex, and five year age group specific incidence rates for the counties where the plants had been located. Altogether 56,022 person-years at risk were generated. RESULTS: A total of 351 incident cancer cases were observed compared to 302 expected, which resulted in an increased standardised incidence ratio (SIR) of 1.16 (95% CI 1.04 to 1.29). An enhanced risk for prostate cancer was observed (SIR 1.44, 95% CI 1.10 to 1.86), mainly attributable to the later part of the observation period (1990-99). In this updated analysis the previously observed risk excess for soft tissue sarcomas was no longer significant (SIR 2.62, 95% CI 0.96 to 5.70). For multiple myelomas and sinonasal cancer the slight non-significant excesses remained, still based on very few cases. CONCLUSIONS: The increased risk for prostate cancer in the present study might be a chance finding, but is noteworthy, since it is in acccordance with the finding of increased SIR for prostate cancer among leather workers in another recent Swedish study. Moreover, excess risks for prostate cancer among farmers have been reported, indicating pesticides as possible causative agents. Leather tanners have also been exposed to pesticides.

Cancer incidence and mortality of isocyanate exposed workers from the Swedish polyurethane foam industry: updated findings 1959-98.

AIMS: To assess whether cancer incidence and mortality in chronic obstructive lung diseases were increased in the Swedish polyurethane foam industry cohort, updated with 11 more years of follow up. METHODS: The mortality and cancer incidence (1959-98) experienced by a cohort of 4175 male and female employees employed for at least one year in the period 1959-87 at one of nine Swedish polyurethane foaming plants were investigated. Comparisons were based on calendar year, sex, and five-year age group specific mortality and incidence rates for Sweden. Workplaces and job tasks were categorically assessed for exposure to toluene diisocyanate (TDI) and methylene diphenyldiisocyanate (MDI) by occupational hygienists. RESULTS: Fewer cancer cases than expected were observed, but the lung cancer incidence was enhanced in women. Women with "apparent exposure" to TDI or MDI did not, however, have a higher lung cancer incidence than those with "no or low exposure". Moreover, a nested case referent study did not find that polyurethane dust exposure had been more prevalent among the female lung cancer cases than among referents. No increased mortality in chronic obstructive lung diseases was observed in the cohort. CONCLUSIONS: Results support the findings from two other cohort studies of an increased lung cancer risk among female workers in the polyurethane foam manufacturing industry. Chance or confounding from smoking are not obvious explanations for the coherent findings. However, the study was not able to link isocyanate exposed employment with lung cancer risk.

Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001.

To ascertain the frequency of treatment-related acute myeloid leukemias and myelodysplastic syndromes (t-AML/t-MDS) in an unselected series, we have identified all adult cases analyzed in our department from 1976 to 1993. Further aims were to compare karyotypic features of t-AML/t-MDS with de novo AML/MDS, in our material as well as in 5098 unselected, cyto- genetically abnormal, published cases, and to analyze associations between type of prior therapy and karyotype. Among our 372 AML and 389 MDS, 47 (13%) were t-AML and 62 (16%) were t-MDS. Clonal abnormalities were significantly more common in t-AML and t-MDS than in de novo disease (68% vs 50%, P < 0.05 and 84% vs 45%, P < 0.001, respectively). Among the available 4230 AML and 1629 MDS (the present series and published cases), 14% were t-AML and 15% were t-MDS. In t-AML/t-MDS, the number of anomalies and the ploidy levels differed significantly from de novo cases, with complex and hypodiploid karyotypes being more common in t-AML/t-MDS. In t-AML, unbalanced changes in general, t(1;3), der(1;7), 3p-, -5, 5q-, -7, 7q-, t(9;11), t(11;19), t(11q23), der(12p), -17, der(17p), -18, and -21 were significantly more frequent than in de novo AML. In t-MDS, -5, -7, 7q-, 13q-, der(17p), and -18 were significantly more common. Type of prior treatment correlated significantly with number of anomalies in t-AML and with ploidy levels in t-AML/t-MDS. The frequencies of several aberrations varied with type of therapy, eg, 5q- was more frequent in radiotherapy-associated t-MDS, monosomy 7 was more common in t-AML and t-MDS after treatment with alkylators, and t(11q23) in t-AML was associated with topoisomerase II inhibitors. Abnormalities significantly more common in de novo disease were +8 as a sole anomaly, balanced changes in general, t(8;21), t(9;22), t(15;17), inv(16), and t(21q22) in AML, and -Y, 5q-, and 20q- as sole anomalies and +8 in MDS. The results emphasize the strong association between previous genotoxic exposure and karyotypic features.

Incidence of asthma in female Swedish hairdressers.

OBJECTIVE: To investigate the risk of asthma in hairdressers. METHODS: The incidence of asthma was retrospectively estimated in a Swedish nationwide study including all female hairdressers certified from vocational schools from 1970 to 1995, and a stratified sample of women from the general population were referents. A postal questionnaire included questions on respiratory tract symptoms, atopy, smoking, working periods as a hairdresser, and number of specific hair treatments performed/week. Reported exposures were validated by occupational hygienists. Rate ratios of incidence (IRRs) of asthma were estimated by Poisson regression, adjusted for calendar year of observation, hay fever, smoking, and region of domicile. RESULTS: The crude incidences of asthma/1000 person-years were: 3.9 during active years as a hairdresser, 2.8 among the hairdressers when not working in the profession, and 3.1 among the referents. The corresponding IRR for being an active hairdresser compared with the referents was 1.3 (95% confidence interval (95% CI) 1.0 to 1.6). Moderate effects on risk of asthma were found both from hairdressing work (IRR=1.6 (1.1 to 2.2) among never-smokers) and from smoking (IRR=1.6 (1.2 to 2.2) among referents). However, the combined effect from hairdressing work and smoking (IRR=1.5 (1.0 to 2.1)) was less than expected (p=0.02). No effect modification by respiratory atopy was found. The hairdressers most often performing hair bleaching treatments (IRR=1.5 (0.7 to 3.0)) or using hair spray (IRR=1.4 (0.8 to 2.4)) had, compared with the most infrequent users, a slightly, but not significantly higher incidence of asthma. Exposure to persulphates in hair bleach was estimated to be 0.04-0.15 mg/m(3) during mixing of the powder. Reported average number of bleaching treatments agreed well with those performed according to a diary. CONCLUSIONS: Active hairdressing work was associated with a moderately increased incidence of asthma among lifelong non-smokers. The results are moderately supportive, but not conclusive, of associations between asthma and exposure to hair bleach or hair spray.

The usefulness of cytogenetic biomarkers as intermediate endpoints in carcinogenesis.

During the last decades, cytogenetic biomarkers in peripheral lymphocytes have been used to assess exposure to carcinogenic or mutagenic agents in occupational settings. The first method in use assessed chromosomal aberrations (CA). It is generally accepted that chromosomal mutations are causal events in the development of neoplasia, and it has earlier been postulated, but not proven, that increased chromosomal damage may reflect an enhanced cancer risk. Two less laborious techniques, sister chromatoid exchanges (SCE) and micronuclei (MN), were introduced later-on in occupational health surveillances. SCE represent symmetrical exchanges between sister chromatids; generally they do not result in alteration of the chromosome morphology. MN represent small, additional nuclei formed by the exclusion of chromosome fragments or whole chromosomes lagging at mitosis. MN rates therefore indirectly reflect chromosome breakage or impairment of the mitotic apparatus. The health significance of increased levels of SCE and MN is poorly understood. The usefulness of these cytogenetic techniques for implementing preventive measures in the workplaces depend on how well they serve as biomarkers of exposure but also on whether they can predict cancer risk or not. Recently performed epidemiological studies show that the CA frequency predicts the overall cancer risk in healthy subjects. Such associations could not been seen for SCE or MN. Age, sex, or time since test did not affect the predictive value of CA. This predictivity was seen irrespective of whether the subjects had been smokers or occupationally exposed to carcinogenic agents. Risk factors such as age, smoking and occupational exposures usually explain only some of the interindividual variation in CA frequency. It seems reasonable that not yet identified individual susceptibility factors explain a large fraction of the interindividual CA variation and also the cancer predictivity of the CA biomarker.

Are occupational, hobby, or lifestyle exposures associated with Philadelphia chromosome positive chronic myeloid leukaemia?

OBJECTIVES: To investigate a broad range of occupational, hobby, and lifestyle exposures, suggested as risk factors for Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML). METHODS: A case-control study, comprising 255 Ph+CML patients from southern Sweden and matched controls, was conducted. Individual data on work tasks, hobbies, and lifestyle exposures were obtained by telephone interviews. Occupational hygienists assessed occupational and hobby exposures for each subject individually. Also, occupational titles were obtained from national registries, and group level exposure-that is, the exposure proportion for each occupational title-was assessed with a job exposure matrix. The effects of 11 exposures using individual data and two exposures using group data (organic solvents and animal dust) were estimated. RESULTS: For the individual data on organic solvents, an effect was found for moderate or high intensity of exposure (odds ratio (OR) 3.4, 95% confidence interval (95% CI) 1.1 to 11) and for long duration (15-20 years) of exposure (OR 2.1, 95% CI 1.1 to 4.0). By contrast, the group data showed no association (OR 0.69, 95% CI 0.27 to 1.8; moderate or high intensity versus no exposure). For extremely low frequency electromagnetic fields (EMFs), only individual data were available. An association with long occupational exposure to EMFs was found (OR 2.3, 95% CI 1.2 to 4.5). However, no effect of EMF intensity was indicated. No significant effects of benzene, gasoline or diesel, or tobacco smoking were found. OR estimates below unity were suggested for personal use of hair dye and for agricultural exposures. CONCLUSIONS: Associations between exposure to organic solvents and EMFs, and Ph+CML were indicated but were not entirely consistent.

The prognostic impact of karyotypic subgroups in myelodysplastic syndromes is strongly modified by sex.

The prognostic impact of karyotypic patterns in a consecutive series of 389 adult myelodysplastic syndromes (MDS) was investigated. Time period did not significantly influence the survival times. In the analyses, the MDS cases were subdivided into the cytogenetic subgroups used in the International Prognostic Scoring System, i.e. favourable [-Y, del(5q) or del(20q) as single aberrations or normal karyotype, n = 241], poor [-7, del(7q), der(1;7) or complex karyotypes, i.e. > or = three abnormalities, n = 89] and intermediate (other aberrations, n = 59). The survival times correlated well with the prognostic subgroups, confirming that the cytogenetic classification was valid. Expressed as hazard ratios (HRs), with the favourable subgroup as the reference, the intermediate and poor subgroup HRs increased to 1.5 (95% confidence interval, 1.1-2.1) and 3.2 (2.4-4.1) respectively. Sex, age, morphological subtype and smoking habits significantly modified this prognostic impact. Shorter survival was detected for men in the favourable and the intermediate subgroups, but not in the poor prognosis subgroup. Using women in the favourable subgroup as the reference and adjusting for age, the HR for men was 1.6 (1.2-2.1) in the favourable subgroup. Adjusting for smoking habits as well decreased the HR to 1.4 (1.1-2.0) and, when also excluding cases with del(5q) as the sole anomaly, no significant difference could be discerned [HR 1.2 (0.9-1.6], suggesting that the better outcome for women in the favourable subgroup was mainly as a result of the '5q-syndrome' and to smoking habits. In the intermediate subgroup, the corresponding HRs were 3.0 (1.5-6.0) when adjusted for age and 2.7 (1.3-5.5) when also adjusted for smoking habits. Different survival times between men and women have never previously been reported for this MDS group. Although it remains to be elucidated whether environmental and/or constitutional factors cause the observed sex-related difference, these observations have obvious clinical ramifications, not least in designing and evaluating therapy protocols.

Incidence of a second tumor in hypopituitary patients operated for pituitary tumors.

Recently, an association between increased blood levels of insulin-like growth factor I (IGF-I) and increased risks of prostate, breast, lung, and colorectal cancers has been suggested. As today adults with GH deficiency are subjected to GH substitution, there is a pressing need for baseline tumor incidence data. The aim of the study was to assess the risk for a second tumor in a cohort of 328 patients with hypopituitarism treated for a pituitary tumor from 1958--1992. The patients were receiving conventional hormone treatment, but without GH substitution. The overall tumor incidence [standardized incidence ratio (SIR)] was lower than expected (0.85), but the 95% confidence interval (CI) did not exclude unity (0.59--1.21). Only two prostate cancers occurred (SIR, 0.34; 95% CI, 0.04--1.24). Two brain tumors (SIR, 1.96; 95% CI, 0.24--7.08) and two endocrine tumors (part of multiple endocrine neoplasm syndromes; SIR, 4.00; 95% CI, 0.48--14.5) had occurred. When excluding brain and endocrine tumors, the overall SIR decreased to 0.77, but did still not differ significantly from unity (0.52--1.13). Thus, a tendency for a decreased overall tumor risk, although not statistically significant, was noted, especially when excluding brain and endocrine tumors. This tendency was more emphasized for prostate cancer, but low numbers hamper a firm conclusion. These results may serve as a baseline for tumor risk among adult patients with pituitary insufficiency supplemented with GH.

Is there an increase in second brain tumours after surgery and irradiation for a pituitary tumour?

OBJECTIVE: To assess the incidence of second brain tumours in patients operated and irradiated for pituitary tumours. DESIGN AND PATIENTS: The study base consisted of a consecutive series of 325 patients operated and irradiated for pituitary tumours, excluding patients with acromegaly and Cushing's disease. Comparison was made with the general population from the same catchment area as the patients. The follow-up period started in 1958 and on an individual basis patients were followed from the onset of postoperative irradiation until December 1995, or until date of death, emigration or a second brain tumour diagnosis, whichever occurred first. RESULTS: Three brain tumours (two astrocytomas and one meningioma) were observed, compared with 1-13 expected (standardized incidence ratios (SIR) 2.7; 95% confidence interval (CI) 0.6-7.8). CONCLUSION: The present study gives no firm support for an increased incidence of a second brain tumour in patients operated and irradiated for pituitary tumours. A crude meta-analysis of the present and previously published cohort studies of patients with irradiated pituitary tumours gives an SIR of 6.1 (95% CI 3.16-10.69). Thus, the results of the meta-analysis are in favour of an increased risk for second brain tumours. A genetic trait that predisposes to both pituitary tumours and brain tumours is an alternative causal factor. There is no definite proof that cranial irradiation per se is the causal factor. This question cannot be fully answered until sufficient cohort studies of nonirradiated pituitary tumour patients have been carried out.

Survival time in a population-based consecutive series of adult acute myeloid leukemia--the prognostic impact of karyotype during the time period 1976-1993.

A consecutive population-based series of 372 adult acute myeloid leukemias, successfully cytogenetically investigated at a single center between 1976 and 1993, is reported. All medical records were reviewed in order to ascertain the prognostic impact of karyotype, divided into three groups; favorable (t(8;21), t(15;17), and inv(16) irrespective of karyotypic complexity; n = 40), poor (der(1;7), inv(3), -5, del(5q), -7, t(9;22), and complex karyotypes including whole or partial losses of chromosomes 5 and/or 7; n = 56), and intermediate (other abnormalities or normal karyotype; n = 276). The possible modification by age, gender, time period, morphologic subtype, and bone marrow transplantation (BMT) on this prognostic impact was also determined. The chemotherapy regimens used were heterogeneous over time but principally the same at any given point in time. The majority of the patients were treated with combinations including an anthracycline and cytarabine with curative intent. Gender, morphology, and BMT did not significantly modify the effect of cytogenetic patterns on survival time, whereas age and time period did. The hazard ratios for the subgroups favorable, intermediate, and poor were 1.0, 1.2 and 1.9 at age 20-49; 1.0, 2.5 and 4.5 at age 50-64; 1.0, 4.1 and 11.4 at age 65-74; 1.0, 1.4 and 2.2 for the time period 1976-1987 and 1.0, 2.0 and 6.7 for 1988-1993. The salient feature of the Kaplan-Meier curves was the improved survival during the later time period for patients with favorable and intermediate cytogenetic abnormalities. The present findings thus suggest that it is mainly these patient groups that have benefited from advances in therapy, including supportive care.

Acute myeloid leukemia and clonal chromosome aberrations in relation to past exposure to organic solvents.

OBJECTIVES: The effects of occupational and leisure-time exposures on the risk of acute myeloid leukemia (AML) were investigated with emphasis on clonal chromosome aberrations (CCA) and morphological subtypes. METHODS: Consecutively diagnosed cases of AML (N=333) and 1 population referent per case were retrospectively included in the study. Information on worktasks, companies, and leisure-time activities was obtained with telephone interviews. Exposure probability and intensity were assessed by occupational hygienists. Associations were evaluated with logistic regression. RESULTS: Exposure to organic solvents was associated with an increased risk of AML [low exposure: OR 1.5 (95% confidence interval (95% CI) 1.0-2.3, moderate-high exposure: OR 2.3 (95% CI 1.0-5.0)]. For exposure to solvents, but not to benzene, the OR was 1.2 (95% CI 0.69-2.0) for "low" and 2.7 (95% CI 1.0-7.3) for "moderate-high" exposure. The observed effects increased with intensity and duration of exposure. The estimated effects were higher for patients >60 years of age at the time of diagnosis. The effect of exposure to organic solvents was not differential with regard to morphology [except possibly erythroleukemia: OR 4.2, 95% CI 1.0-17 or the presence of CCA in general]. No increased risk for AML with complex CCA or with total or partial losses of chromosomes 5 or 7 were observed, but a higher risk was found for AML with trisomy 8 (OR 11, 95% CI 2.7-42) as the sole aberration. CONCLUSIONS: Exposure to organic solvents was associated with an increased risk of AML. This association was not due to benzene exposure alone and may be modified by age. Furthermore, specific associations with trisomy 8, and possibly also erythroleukemia, were suggested.

A single-center population-based consecutive series of 1500 cytogenetically investigated adult hematological malignancies: karyotypic features in relation to morphology, age and gender.

During the 18-yr period 1976-93, a population-based series of 1586 adults with suspected or confirmed hematological malignancies were successfully cytogenetically investigated at a single center. Eighty-six cases were excluded due to unretrievable medical records or if analyzed only in remission or at relapse. The remaining 1500 medical records were reviewed regarding morphology and clinical parameters in order to investigate possible associations between karyotypic pattern (normal, 1, 2 or complex anomalies; specific abnormalities) and gender, age and morphological subgroups. The impact of time-period, i.e. 1976-87 vs. 1988-93, and referring center on cytogenetic findings was also studied. A total of 372 acute myeloid leukemias (AML), 389 myelodysplastic syndromes (MDS), 64 acute lymphoblastic leukemias (ALL) and 262 chronic myeloid leukemias (CML) were identified, altogether 1087 cases. Patients with other (n=261) or no hematological malignancies (n = 152) were excluded from the present analysis. Cytogenetic abnormalities were detected in 52% AML, 51 % MDS, 68% ALL and 97% CML, frequencies that did not differ significantly between the 2 time periods or referring centers. No significant age- or gender-related differences in karyotypic patterns were discerned in AML, MDS, ALL or CML, whereas the karyotypic patterns varied among the FAB groups in both AML (p= 0.001) and MDS (p < 0.001). The specific abnormalities t(8;21), t(15;17) and inv(16) were more common (p < 0.001) in younger AML patients and 5q- was more frequent in females with MDS (p<0.001). These findings indicate, in contrast to previous series, that neoplasia-associated karyotypic aberrations are not more common among older patients or in males.

Cancer incidence in a cohort of Swedish sewage workers: extended follow up.

OBJECTIVES: To study the cancer incidence in a cohort of Swedish sewage workers. An increased incidence of cancer of the stomach, the kidney and the nervous system in this cohort was previously reported. This new analysis reports on 9 more years of follow up. METHODS: The study is an analysis of a cohort of all 711 employees at 17 Swedish sewage plants employed for at least for 1 year during the years 1965-86. Assessment of exposures was performed by classification of work tasks. Standardised incidence ratios (SIRs), and 95% confidence intervals (95% CIs) were calculated. RESULTS: The total cancer incidence was not significantly increased (SIR = 1.2, 95% CI 0.92 to 1.5) but the incidence of prostate cancer was (SIR = 1.6, 95% CI 1.0 to 2.5), and based on two cases only, there seemed to be a significant increase of cancer of the nose and the nasal sinuses (SIR = 12, 95% CI 1.5 to 44). The incidence of stomach cancer was also increased (SIR = 2.3, 95% CI 0.99 to 4.5). There was no relation between cancer incidence and level of sewage exposure. CONCLUSIONS: Sewage workers did not have an increased risk of cancer, and the increased risk estimates for some specific cancer sites were not conclusive.

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health.

The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

K-ras mutations in sinonasal adenocarcinomas in patients occupationally exposed to wood or leather dust.

Of 39 males diagnosed with sinonasal adenocarcinomas over 30 years in the Lund University Hospital catchment area (1.5 million inhabitants), archival tumor tissue was available from 29. Of these, 16 had been exposed to wood dust and three had been exposed to leather dust. The intestinal-type and papillary adenocarcinomas were more common in the exposed patients (P = 0.0002, Fisher's exact test). The tumors from all but one of the 29 sinonasal adenocarcinomas could be analyzed for point mutations at codons 12, 13 and 61 of the K-ras gene. Four mutations were detected in the 28 tumors. The three mutations in the patients exposed to wood and leather dust were all G:C --> A:T transitions, with two at position 2 of codon 12 and one at position 2 of codon 13. The high proportion of G:C --> A:T mutations in this rare tumor may reflect a genotoxic agent in wood and leather dust.

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs.

It has not previously been clear whether cytogenetic biomarkers in healthy subjects will predict cancer. Earlier analyses of a Nordic and an Italian cohort indicated predictivity for chromosomal aberrations (CAS) but not for sister chromatid exchanges (SCES). A pooled analysis of the updated cohorts, forming a joint study base of 5271 subjects, will now be performed, allowing a more solid evaluation. The importance of potential effect modifiers, such as gender, age at testing, and time since testing, will be evaluated using Poisson regression models. Two other potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

Increased cerebrovascular mortality in patients with hypopituitarism.

OBJECTIVE: An increased prevalence of atherosclerosis has been shown among patients with hypopituitarism. The aim of the present study was to assess whether patients with hypopituitarism experience increased cardiovascular, in particular cerebrovascular, mortality. DESIGN AND PATIENTS: Retrospective cohort study of mortality, 1952-1992, in 344 patients, of whom 130 were female, receiving conventional hormone replacement for hypopituitarism following neurosurgery for pituitary tumours. The general population in the catchment area of southern Sweden from which the patients were recruited constituted the reference population. Expected mortality was obtained from cause, sex, calendar year, and 5-year age-specific death raise for the area. RESULTS: Increased mortality from cerebrovascular disease (standardized mortality ratio (SMR) 3.39; 95% CI 2.27-4.99) was the main contributor to the increased overall cardiovascular mortality (SMR 1.75; 95% CI 1.40-2.19). The increase in mortality from cardiac diseases was much smaller (SMR 1.41; 95% CI 1.04-1.88). The risk for cerebrovascular death was higher in women (SMR 4.91) than in men (SMR 2.64). The relative risk for cerebrovascular death was independent of the time interval since diagnosis of pituitary insufficiency, but was greater in subjects diagnosed at an earlier age (< 55 years). No increased mortality in malignant tumours was observed (SMR 0.95; 95% CI 0.60-1.48). CONCLUSION: The increased cerebrovascular mortality may be due to GH deficiency, or to long-term lack or inadequacy of substitution for other pituitary hormones. The observations that an early onset of pituitary insufficiency and female sex are predictors for a high risk for cerebrovascular mortality merit particular attention when treating this group of patients.

Deaths and tumours among workers grinding stainless steel: a follow up.

OBJECTIVE: To study cause specific mortality and cancer morbidity in workers exposed to the dust of grinding materials, grinding agents, and stainless steel, especially with regard to a possibly increased risk of respiratory, stomach, and colorectal cancer. METHODS: Retrospective cohort study, using reference cohorts of blue collar workers and population rates for comparison. The exposed cohort comprises workers with at least 12 months employment time at two plants, producing stainless steel sinks and saucepans (n = 727). Also, reference cohorts of other industrial workers (n = 3965) and fishermen (n = 8092) were analysed. The observation period began 15 years after the start of employment. Standardised mortality or incidence ratios (SMRs, SIRs; county reference rates) were calculated for cause-specific mortality between 1952 and 1993, and for cancer morbidity between 1958 and 1992. RESULTS: In the exposed cohort, overall mortality, cardiovascular mortality, and all malignant mortality and morbidity were slightly lower than expected. Also, the risk estimates for cancer in the upper and lower respiratory tracts and for stomach cancer were lower than expected. There was an increase in morbidity from colon cancer, which was explained by an excess of tumours in the sigmoid part only. Here, the risk estimates were higher in workers with long employment time (1-14 years: four observed cases, SIR 1.7, 95% confidence interval (95% CI) 0.4 to 4.5; > or = 15 years: three observed cases, SIR 4.3, 95% CI 0.9 to 13) and the increased risk was especially pronounced among those first employed before 1942. A slight nominal excess of rectal cancers (nine observed cases, SIR 1.4, 95% CI 0.6 to 2.6), and a significant excess of prostate cancer morbidity (36 observed cases, SIR 1.7, 95% CI 1.2 to 2.4) were found. These risk estimates did not, however, increase with employment time. CONCLUSIONS: The finding of an increased risk of cancer in the sigmoid part of the colon, which was not found in the reference cohorts, and with indication of a relation between duration of employment and response, is consistent with a causal relation. The limited size of the exposed cohort makes a detailed exposure-response analysis unstable, and the confidence limits are wide. Albeit slightly raised, the risk estimate for rectal cancer in the exposed cohort was not different from the estimate among the other industrial workers.

Cancer incidence and specific occupational exposures in the Swedish leather tanning industry: a cohort based case-control study.

OBJECTIVE: To study the effect on the incidence of cancer of exposure to chemicals handled in the leather tanning industry. MATERIALS AND METHODS: A case-control study was performed within a cohort of 2487 workers employed for at least six months during the period 1900-89 in three Swedish leather tanneries. 68 cancer cases (lung, stomach, bladder, kidney, nasal, and pancreatic cancers and soft tissue sarcomas) and 178 matched controls were studied. Effects of chemical exposures on cancer incidence, adjusted for age at risk, sex, and plant were estimated with a conditional logistic regression model. RESULTS: A significant association was found between exposure to leather dust and pancreatic cancer (odds ratio (OR) 7.19, 95% confidence interval (95% CI) 1.44 to 35-89). An association was indicated between leather dust from vegetable tanning and lung cancer. After adjustment for smoking habits a tentative association between organic solvents and lung cancer lost its significance. No association was found between exposure to chlorophenols and soft tissue sarcomas. CONCLUSIONS: The significant association between leather tanning and soft tissue sarcomas that was found in our previous cohort analysis could not be explained by exposure to chlorophenols. On the other hand a significant association was found between exposure to leather dust and pancreatic cancer, and exposure to leather dust from vegetable tanning was often present in cases with lung cancer. Due to the small numbers of cases, the results can, however, only lead to tentative conclusions.