Associations between estimated acrylamide intakes, and hemoglobin AA adducts in a sample from the Malmö Diet and Cancer cohort.

OBJECTIVE: To examine the coherence of estimated intakes of acrylamide (AA) from foods, with hemoglobin (Hb) AA adduct levels, an objective marker of environmental AA exposure. DESIGN: A cross-sectional study. SETTING: The Malmö Diet and Cancer study, a large population-based prospective cohort (n=28 098) in the south of Sweden. SUBJECTS: A sample of non-smoking (n=70) and smoking (n=72) women and men selected to obtain large variation in Hb AA adducts. METHODS: Self-reported data on the usual consumption of foods were combined with published data on the AA content in Swedish foods. The Hb AA adduct levels were determined by a modified Edman degradation method. Linear regression and correlation analysis examined associations between estimated AA intakes, and Hb AA adducts. RESULTS: In randomly selected individuals (n=40), the estimated median AA intake was 28 mug per day. In linear regression models, adjusting for sex, significant associations were seen in non-smokers between Hb AA adducts and estimated AA from foods (P=0.006). In smokers both AA from foods (P=0.006) and the calculated amount of tobacco consumed (P=0.003) were significantly associated with Hb AA adducts. Positive partial correlations between dietary AA estimates and Hb AA adducts were seen in smoking men (r=0.37) and women (r=0.59), and in non-smoking men (r=0.60), but not in non-smoking women. CONCLUSIONS: This study suggests that both diet and tobacco are important sources of the environmental AA exposure, although the lack of correlations in non-smoking women cast doubt on the validity of dietary AA intake estimates used in cancer epidemiology, or suggest that unrecognized factors may influence the internal dose measure of AA exposure.

Androgen receptor gene GGN repeat length and reproductive characteristics in young Swedish men.

BACKGROUND: The human androgen receptor (AR) gene contains two polymorphisms of CAG and GGN repeats respectively. The GGN repeat function is still largely unknown and to date there are no in vivo data on this segment with respect to the general population. METHODS: We investigated the impact of CAG and GGN repeats on male reproductive function, one by one and in interaction with each other, in 220 adolescent men from the general Swedish population. Physical examination and semen analysis, including accessory sex gland markers and measurement of reproductive hormone levels, were performed. Lifestyle-associated factors, including maternal smoking during pregnancy, were recorded. GGN and CAG repeat lengths were determined by sequencing. RESULTS: GGN<23 was associated with lower semen volume when compared to GGN=23 (mean difference -0.6 ml, P=0.02) and GGN>23 (mean difference -0.9 ml, P=0.002). Men with GGN<23, exposed to maternal smoking during pregnancy, had higher body mass index compared to men with other GGN lengths, no matter whether their mother had smoked or not during pregnancy (mean difference 4.8 kg/m2, P<0.001). CONCLUSIONS: Short GGN repeats seem to be associated with decreased semen volume, possibly due to suboptimal AR activity. Body composition may be influenced by the combination of fetal exposure to maternal smoking and certain AR genotypes.

Chromosomal aberrations and SCEs as biomarkers of cancer risk.

Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.

Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH).

Chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronuclei (MN) in peripheral blood lymphocytes have for decades been used as cytogenetic biomarkers to survey genotoxic risks in the work environment. The conceptual basis for this application has been the idea that increased cytogenetic damage reflects an enhanced cancer risk. Nordic and Italian cohorts have been established to evaluate this hypothesis, and analyses presented previously have shown a positive trend between CA frequency and increased cancer risk. We now report on a pooled analysis of updated data for 3541 subjects examined for CAs, 2703 for SCEs, and 1496 for MN. To standardize for interlaboratory variation, the results for the various cytogenetic end points were trichotomized on the basis of the absolute value distribution within each laboratory as "low" (1-33 percentile), "medium" (34-66 percentile), or "high" (67-100 percentile). In the Nordic cohort, there was an elevated standardized incidence ratio (SMR) for all cancer among subjects with high CA frequency [1.53; 95% confidence interval (CI), 1.13-2.05] but not for those with medium or low CA frequency. In the Italian cohort, a SMR in cancer of 2.01 (95% CI, 1.35-2.89) was obtained for those with a high CA frequency level, whereas the SMRs for those with medium or low did not noticeably differ from unity. Cox's proportional hazards models gave no evidence that the effect of CAs on total cancer incidence/mortality was modified by gender, age at test, or time since test. No association was seen between the SCEs or the MN frequencies and subsequent cancer incidence/mortality. The present study further supports our previous observation on the cancer predictivity of the CA biomarker, which seems to be independent of age at test, gender, and time since test. The risk patterns were similar within each national cohort. This result suggests that the frequency of CAs in peripheral blood lymphocytes is a relevant biomarker for cancer risk in humans, reflecting either early biological effects of genotoxic carcinogens or individual cancer susceptibility.

Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health.

An increased risk of cancer in healthy individuals with high levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes has been described in recent epidemiological studies. This association did not appear to be modified by sex, age, country, or time since CA test, whereas the role played by exposure to carcinogens is still uncertain because of the requisite information concerning occupation and lifestyle was lacking. We evaluated in the present study whether CAs predicted cancer because they were the result of past exposure to carcinogens or because they were an intermediate end point in the pathway leading to disease. A nested case-control study was performed on 93 incident cancer cases and 62 deceased cancer cases coming from two prospective cohort studies performed in Nordic countries (Denmark, Finland, Norway, and Sweden) and Italy. For each case, four controls matched by country, sex, year of birth, and year of CA test were randomly selected. Occupational exposure and smoking habit were assessed by a collaborative group of occupational hygienists. Logistic regression models indicated a statistically significant increase in risk for subjects with a high level of CAs compared to those with a low level in the Nordic cohort (odds ratio, 2.35; 95% confidence interval, 1.31-4.23) and in the Italian cohort (odds ratio, 2.66; 95% confidence interval, 1.26-5.62). These estimates were not affected by the inclusion of occupational exposure level and smoking habit in the regression model. The risk for high versus low levels of CAs was similar in subjects heavily exposed to carcinogens and in those who had never, to their knowledge, been exposed to any major carcinogenic agent during their lifetime, supporting the idea that chromosome damage itself is involved in the pathway to cancer. The results have important ramifications for the understanding of the role played by sporadic chromosome damage for the origin of neoplasia-associated CAs.

Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage.

Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange or micronuclei in PBL. In order to standardize for the interlaboratory variation, the results were trichotomized for each laboratory into three strata: low (1-33 percentile), medium (34-66 percentile), or high (67-100 percentile). In this second follow-up, a total of 85 cancers were diagnosed during the observation period (1970-1991). There was no significant trend in the standardized incidence ratio with the frequencies of sister chromatid exchange or micronuclei, but the data for these parameters are still too limited to allow firm conclusions. There was a statistically significant linear trend (P = 0.0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk.

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.

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.

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 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.

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.

Hypopituitary females have a high incidence of cardiovascular morbidity and an increased prevalence of cardiovascular risk factors.

We recently reported that female patients with hypopituitarism receiving controlled thyroid and steroid hormone substitution, but without GH replacement, had a more than 2-fold increase in cardiovascular mortality compared to the general population. In the present study we investigated the incidence of cardiovascular disease as well as the prevalence of cardiovascular risk factors in 33 females with hypopituitarism for 6-46 yr (median, 18) compared to those in 33 control subjects recruited from the general population in the same geographical area and matched for sex, age, smoking habits, educational level, and residence location. The patients were with a very high probability GH deficient, as 29 had subnormal serum insulin-like growth factor I levels, and the other 4 were GH deficient, as assessed by an insulin tolerance test. The incidence of cardiovascular disease was significantly higher among the hypopituitary patients (incidence ratio, 3.7; 95% confidence interval, 1.2-11.3), and the consumption of cardioactive drugs was also significantly higher (P = 0.002). Hypopituitary patients had a lower degree of physical exercise during their spare time (P = 0.02), a higher waist/hip ratio (P = 0.01), lower high density lipoprotein cholesterol (P = 0.002), and higher low density/high density lipoprotein ratio (P = 0.009). Furthermore, the patients had a significantly increased left atrium size (P = 0.05), but no difference was observed for other cardiac measures. In the patients, serum insulin-like growth factor I levels significantly correlated with left ventricular mass index (r = 0.48; P = 0.006), suggesting that GH has a strong impact on cardiac size. More episodes of bradycardia (P = 0.05), but no increased occurrence of extrasystolies, were encountered in the patients during 24-h continuous electrocardiogram monitoring. Carotid artery intima-media thickness and plaque numbers did not differ between patients and controls. In conclusion, hypopituitary females exhibit an increased incidence of cardiovascular disease, higher cardioactive drug consumption, and an increased prevalence of cardiovascular risk factors. The increased cardiovascular morbidity could not be ascribed to inadequate estrogen or thyroid hormone treatment, and unsubstituted GH deficiency is probably an important contributing factor.

Postoperative prognosis in craniopharyngioma with respect to cardiovascular mortality, survival, and tumor recurrence.

Specific causes of death, survival, and recurrence rates were assessed in a cohort of 60 patients who had undergone surgery for craniopharyngioma between 1951 and 1988. Compared to the general population, the standardized mortality ratio (SMR) was increased [5.55; 95% confidence interval (CI), 3.68-8.22], and it was higher among females (SMR, 11.4) than males (SMR, 4.79). The risk of cardio- and cerebrovascular mortality (SMR, 3.21; 95% CI, 1.29-6.61) was also enhanced. The cumulative survival rates 10 and 15 yr after the initial operation were 68% (95% CI 54-78) and 59% (95% CI 30-63), respectively. A multivariate survival analysis adjusting for age showed a protective effect of radiotherapy (hazard ratio, 0.3; 95% CI, 0.1-0.8) and an increased risk of death after recurrence (hazard ratio, 4.4; 95% CI, 1.4-14), but no obvious effect of radicality at surgery. However, when patients who had died within 6 months after surgery were excluded, no significant protective effect of radiotherapy remained. The cumulative frequency of recurrence after 10 yr was 33% (95% CI, 22-48%), and that after 15 yr was 40% (95% CI, 28-56%). The incidence of recurrence did not differ significantly with respect to age, radicality at surgery, or postoperative radiotherapy. The determinants for long term outcome in patients with craniopharyngioma are interrelated in a complex way, which calls for strict selection criteria in follow-up studies and the use of multivariate statistical models.

Chromosomal aberrations and risk of cancer in humans: an epidemiologic perspective.

The pioneering papers published more than one century ago by Theodor Boveri opened the way to extensive research on the mechanism linking chromosomal abnormalities to the pathogenesis of cancer. As a result of this effort, robust theoretical and empirical evidence correlating cytogenetic damage to early stages of cancer in humans was consolidated, and an increased cancer risk was postulated in healthy subjects with high levels of chromosomal aberrations (CA). The first epidemiological investigation aimed at validating CA as predictor of cancer risk was carried out in the early 1990s. In that report the Nordic Study Group described an 80% increased risk of cancer in healthy subjects with high frequencies of CA. The results of this first study were replicated a few years later in a parallel research initiative carried out in Italy, and the subsequent pooled analysis of these two cohorts published in 1998 contributed to refine the quantitative estimate of the CA/cancer association. A small case-control study nested in a cohort of subjects screened for CA in Taiwan found an increased risk in subjects with high frequency of chromosome-type CA, while in 2001 a significant increase of cancer incidence associated with high levels of CA was described in a new independent cohort of radon exposed workers from the Czech Republic. Despite some common limitations affecting study design, the studies cited above have provided results of great interest both for the understanding of mechanisms of early stages of carcinogenesis, and for their potential implication for cancer prevention. The recent evolution of molecular techniques and the refinement of high throughput techniques have the potential to improve the knowledge about the role of specific sub-types of CA and to provide further insight into the mechanisms. Finally, the most challenging perspective in the field is the passage from research to regulation, with the implementation of preventive policies based on the accumulated knowledge.

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.

Influence of the consumption of fatty Baltic Sea fish on plasma levels of halogenated environmental contaminants in Latvian and Swedish men.

We examined the influence of widely varied consumption of fatty fish from the Baltic Sea and of age on plasma concentrations of polychlorinated biphenyls (PCBs), polychlorobiphenylols (OH-PCBs), 2, 2-bis(4-chlorophenyl)-1,1,1-trichloroethane (4,4'-DDT), 2, 2-bis(4-chlorophenyl)-1,1-dichloroethane (4,4'-DDE), 2,2',4, 4'-tetrabromodiphenyl ether (BDE-47), hexachlorobenzene (HCB), and pentachlorophenol (PCP) in Latvian and Swedish men. Both age and fish consumption were significantly correlated with the concentrations of [sigman]PCB, [sigman]OH-PCB, 4,4'-DDE, 4,4'-DDT, and HCB. In the case of BDE-47, no significant relationship with age was observed, and fish consumption had the largest relative effect on plasma concentrations of this contaminant. This relationship may be a result of exposure to BDE-47 having been more recent than that of PCBs and DDE, or because the half-life of BDE-47 may be shorter than that of PCB and DDE. Latvian men demonstrated higher plasma levels of DDE and DDT but lower levels of [sigman]PCB and PCP than did Swedish men. The corresponding levels of HCB and BDE-47 were similar in both countries. The Spearman's rank correlation coefficient obtained by comparing the level of the metabolite 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to the combined levels of its parent compounds, 2,3,3',4, 4'-pentachlorobiphenyl (CB-105) and 2,3',4,4',5-pentachlorobiphenyl (CB-118), was higher than the median correlation coefficient obtained upon comparing the level of this metabolite to all other possible combinations of two PCB levels. No other increased correlation between metabolite and parent PCB concentration was observed.

Flame retardant exposure: polybrominated diphenyl ethers in blood from Swedish workers.

Polybrominated diphenyl ethers (PBDEs) are used as additives in polymers and textiles to prohibit the development of fires. Because of the production and use of PBDEs, their lipophilic characteristics, and persistence, these compounds have become ubiquitous environmental contaminants. The aim of the present study was to determine potential exposures of PBDEs to clerks working full-time at computer screens and personnel at an electronics-dismantling plant, with hospital cleaners as a control group. Five PBDE congeners--2,2',4,4'-tetraBDE; 2,2',4,4',5,5'-hexaBDE; 2,2',4,4',5, 6'-hexaBDE; 2,2',3,4,4',5',6-heptaBDE; and decaBDE--were quantified in blood serum from all three categories of workers. Subjects working at the dismantling plant showed significantly higher levels of all PBDE congeners in their serum as compared to the control group. Decabromodiphenyl ether is present in concentrations of 5 pmol/g lipid weight (lw) in the personnel dismantling electronics; these concentrations are comparable to the concentrations of 2,2',4, 4'-tetraBDE. The latter compound was the dominating PBDE congener in the clerks and cleaners. The major compound in personnel at the dismantling plant was 2,2',3,4,4',5',6-heptaBDE. Concentrations of this PBDE congener are almost twice as high as for 2,2',4, 4'-tetraBDE in these workers and seventy times the level of this heptaBDE in cleaners. The total median PBDE concentrations in the serum from workers at the electronics-dismantling plant, clerks, and cleaners were 37, 7.3, and 5.4 pmol/g lw, respectively. The results show that decabromodiphenyl ether is bioavailable and that occupational exposure to PBDEs occurs at the electronics-dismantling plant.

Smoking and acute myeloid leukemia: associations with morphology and karyotypic patterns and evaluation of dose-response relations.

This case-control study of tobacco smoking and acute myeloid leukemia (AML), emphasizing specific associations with morphologic and cytogenetic subtypes, comprised smoking histories for 333 cases and 351 controls. Smoking status (ever smokers versus life-long non-smokers) showed no evident effect on AML risk. However, an effect of smoking was indicated at high cumulative smoking doses (pack-years), e.g. 40 pack-years was associated with an odds ratio (OR) of 1.5 [95% confidence interval (CI) 1.0-2.3]. Among morphologic subtypes, the smoking associated OR for acute erythroleukemia was 8.9 (95% CI 1.0-76). No clear associations between smoking and cytogenetic subtypes of AML were observed.

Decreased serum testosterone and free triiodothyronine levels in healthy middle-aged men indicate an age effect at the pituitary level.

In an attempt to study further the age-specific influence on the hypothalamo-pituitary-gonadal axis as well as the hypothalamo-pituitary-thyroid axis, we have now investigated young and middle-aged men, considering possible confounding factors. Both serum total testosterone, free testosterone and the total ratio of testosterone to sex-hormone binding globulin were significantly lower among middle-aged men as compared with young men (p = 0.02, p = 0.002 and p = 0.0003, respectively). In accordance with these findings there was also a decrease in the luteinizing hormone response to gonadotrophin-releasing hormone in the middle-aged men (p = 0.02). Free testosterone was correlated significantly with the luteinizing hormone response (r = 0.32, p = 0.02). Serum free triiodothyronine was significantly higher among young men as compared with middle-aged men (p = 0.002) and the thyrotrophin-releasing hormone-stimulated thyrotrophin response was also higher in the young group compared with the middle-aged group. The present results may indicate that the age effect on serum levels of testosterone and free triiodothyronine is mediated at the pituitary level.

An inter-Nordic prospective study on cytogenetic endpoints and cancer risk. Nordic Study Group on the Health Risk of Chromosome Damage.

To investigate whether high rates of chromosomal aberrations (CAs), sister chromatid exchange (SCE), or micronuclei(MN) in peripheral lymphocytes indicate an increased risk for subsequent cancer, a prospective cohort study of 2,969 subjects cytogenetically examined between 1970 and 1988 in four Swedish, two Finnish, and two Norwegian laboratories was initiated. To standardize for the interlaboratory variation, the results of the three cytogenetic endpoints were trichotomized for each laboratory into "low" (1st to 33rd percentile), "medium" (34th to 66th percentile), and "high" (67th to 100th percentile]. Thirty-four cancers had been diagnosed in the cohort during the observation period (1970 to 1985). The point-estimates of the standardized morbidity ratio (SMR) in the three CA strata were 90, 92, and 180, respectively. This trend for a positive association was not statistically significant (p = 0.06). There was no significant trend between SMR and the trichotomized rates of SCE. In the subcohort examined for MN only two cases of cancer had been diagnosed until now. If subjects with "high" frequencies of CA or SCE have a two-fold (or greater) risk of developing cancer as compared with individuals who have "medium" or "low" frequencies, we estimate that there is a likelihood of 80% and 70%, respectively, that this will be detectable as significant (p less than or equal to 0.05) differences after a further follow-up period of 5 years. Weaker associations between cancer risk and the cytogenetic endpoints would not be possible to evaluate until even later follow-ups.