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.

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.

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.

Factors affecting time to pregnancy.

BACKGROUND: Both lifestyle factors and occupational and environmental factors have been suggested to affect the female reproductive system. In the present study, the separate and joint effects of several such factors are investigated. METHODS: Information on time to pregnancy (TTP) was available for 1578 women randomly selected from the general Swedish population. The information was collected retrospectively by using self-administered questionnaires. By means of logistic regression of survival data, fecundability odds ratios were determined for many factors. Multivariate models were used to determine which factors had the most impact on TTP. RESULTS: Several lifestyle factors were found to associate with TTP. However, only use of oral contraceptives prior to attempting to conceive, menstrual cycle length, age at conception and parity remained in the multivariate models. Together, these factors explained 14% of the variance in TTP. Excluding first and second month conceptions, only age at conception and menstrual cycle length remained in the multivariate models, together explaining only 8% of the variance in TTP. CONCLUSIONS: Although information on several factors was available, the multivariate model explained only a small fraction of the variation in the observed time to pregnancies. Furthermore, female biological factors seemed more important predictors of TTP than lifestyle factors.

Time to pregnancy as a function of male and female serum concentrations of 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE).

BACKGROUND: Persistent organochlorine pollutants (POP) may affect both the female and male reproductive system in animals as well as in humans. METHODS: Blood samples were collected from pregnant women and their partners from Greenland, Warsaw and Kharkiv, and from a cohort of Swedish fishermen's wives. Blood samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE). Information on the participants' fertility, measured as time to pregnancy (TTP), was collected. In total, 778 men and 1505 women were included in the analyses. RESULTS: The data from Warsaw, Kharkiv and the Swedish fishermen's wives indicated no effect of either male or female exposure to POP on TTP. However, among men and women from Greenland, there seemed to be an association between serum concentrations of CB-153 and p,p'-DDE and prolonged TTP. Due to the strong intra-individual correlation between CB-153 and p,p'-DDE in the Greenlandic population, it was not possible to determine whether the risk was associated with CB-153 or p, p'-DDE or was an interaction between the two compounds. CONCLUSIONS: The overall results of the present study create a somewhat ambiguous pattern, but give some support to the idea that dietary POP exposure might be harmful for couple fertility.

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.

Exposure to PCB and p, p'-DDE in European and Inuit populations: impact on human sperm chromatin integrity.

BACKGROUND: Persistent organochlorine pollutants (POP), such as polychlorinated biphenyls (PCB) and dichlorodiphenyldichloroethylene (p, p'-DDE), are widely found in the environment and considered potential endocrine-disrupting compounds (EDC). Their impact on male fertility is still unknown. METHODS: To explore the hypothesis that POP is associated with altered sperm chromatin integrity, a cross-sectional study involving 707 adult males (193 Inuits from Greenland, 178 Swedish fishermen, 141 men from Warsaw, Poland, and 195 men from Kharkiv, Ukraine) was carried out. Serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), as a proxy of the total PCB burden, and of p,p'-DDE were determined. Sperm chromatin structure assay (SCSA) was used to assess sperm DNA/chromatin integrity. RESULTS: We found a strong and monotonically increasing DNA fragmentation index with increasing serum levels of CB-153 among European but not Inuit men, reaching a 60% higher average level in the highest exposure group. No significant associations were found between SCSA-derived parameters and p, p'-DDE serum concentrations. CONCLUSION: These results suggest that human dietary PCB exposure might have a negative impact on the sperm chromatin integrity of adult males but additional issues, including differences in the genetic background and lifestyle habits, still need to be elucidated.

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.

Exposure to persistent organochlorine pollutants and seminal levels of markers of epididymal and accessory sex gland functions in Swedish men.

BACKGROUND: A major exposure route for persistent organochlorine pollutants (POPs) in Sweden is through consumption of fatty fish from the Baltic Sea. Endocrine disruptors, such as POPs, may have a negative impact on sperm quality. The present study aimed to investigate whether exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) affects epididymal and accessory sex gland function. METHODS: 157 fishermen from the coastal stretches of Sweden, aged 27-67 years, provided semen samples which were analyzed for prostate-specific antigen (PSA), neutral alpha-glucosidase (NAG), fructose and zinc levels. Serum levels of CB-153 and p'p-DDE were determined. RESULTS: The median CB-153 serum level was 189 ng/g lipid (range 40-1460) and a median p,p'-DDE serum level 231 ng/g lipid (range 40-2252). There was a significant linear association between CB-153 and total amount of PSA (slope [beta] = -2.5, 95% confidence interval [CI] -4.0, -0.9; P = 0.02). With age, abstinence time and smoking included in the model the association became non-significant (beta = -1.4, 95% CI-3.0, 0.1; P = 0.07). There were no significant associations between CB-153 and zinc, fructose and NAG. As for the exposure variable p,p'-DDE and the outcome variables, no significant associations were found. CONCLUSIONS: The study gives only very limited support of an association between CB-153 in serum and total PSA, and a random finding cannot be excluded.

Exposure to CB-153 and p,p'-DDE and male reproductive function.

BACKGROUND: During the last decades, there has been concern that exposure to endocrine disruptors, such as persistent organochlorine pollutants (POPs), may contribute to an impairment of male reproductive function. To investigate whether exposure to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) affects semen quantity and quality and reproductive hormones, 195 Swedish fishermen, aged 24-65 years, were investigated. METHODS: The men provided semen samples which were analysed in a mobile laboratory unit. Blood samples and information relating to lifestyle, medical and reproductive history were obtained. RESULTS: The subjects had a median CB-153 serum level of 193 ng/g lipid (range 39-1460) and a median p,p'-DDE serum level of 240 ng/g lipid (range 334-2251). When CB-153 was categorized into quintiles, the subjects in the quintile with the highest concentration (> 328 ng/g lipid), tended to have decreased sperm motility compared with the subjects in the lowest quintile (< 113 ng/g lipid). The age-adjusted mean difference was 9.9% (95% confidence interval -1.0 to 21% P = 0.08). We found no significant associations between p,p'-DDE and semen characteristics or reproductive hormones. CONCLUSION: The association between CB-153 and sperm motility, although not formally significant, is of interest considering the possible endocrine-disrupting effects of polychlorinated biphenyls (PCBs).

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.

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.

Retrospective exposure assessment and quality control in an international multi-centre case-control study.

The paper presents the exposure assessment method and quality control procedure used in an international, multi-centre case-control study within a joint Nordic and Italian cohort. This study was conducted to evaluate whether occupational exposure to carcinogens influenced the predictivity of high frequency of chromosomal aberrations (CA) in peripheral lymphocytes for increased cancer risk. Occupational hygienists assessed exposures in each participating country: Denmark, Finland, Italy, Norway and Sweden. The exposure status to a carcinogen or a clastogen was coded in the cohort according to the original CA studies at the time of CA testing, but not for the whole work life. An independent occupational hygienist coordinated harmonization of the assessment criteria and the quality control procedure. The reliability of the exposure assessments was calculated as deviation from the majority of the assessors, as Cohen's kappa and as overall proportion of the agreements. The reassessment of the exposures changed the exposure statuses significantly, when compared with the original cohort. Harmonization of the exposure criteria increased the conformity of the assessments. The prevalence of exposure was higher among the original assessors (the assessor from the same country as the subject) than the average prevalence assessed by the other four in the quality control round. The original assessors classified more job situations as exposed than the others. Several reasons for this are plausible: real country-specific differences, differences in information available to the home assessor and the others and misunderstandings or difficulties in translation of information. To ensure the consistency of exposure assessments in international retrospective case-control studies it is important to have a well-planned study protocol. Due to country-specific environments a hygienist from each participating country is necessary. A quality control study is recommended, to be performed as described, combined with round-table meetings to minimize information bias between the assessors.

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.

Higher sperm counts in Southern Sweden compared with Denmark.

BACKGROUND: A common aetiology behind time-related deterioration of male reproductive function, including decline of sperm concentration and rising incidence of testicular cancer and cryptorchidism, has been suggested. Accordingly, a high incidence of testicular cancer and low sperm counts have been observed in Denmark, while in Finland opposite figures were found. This may be due to genetic factors. The incidence of testicular cancer is 50% lower in Sweden than in Denmark. Data on sperm counts in a population of Danish military conscripts have been published and we wished therefore to compare them with semen parameters in a corresponding cohort from Southern Sweden, geographically and genetically very closely related to Denmark. METHODS: A total of 305 military conscripts was recruited and investigated in an identical way as those in the Danish study including a questionnaire, physical examination and semen analysis. RESULTS: Men born and raised in Sweden had a 23% higher mean sperm concentration, a 31% higher mean total sperm count and a 14% higher seminal volume compared with their Danish counterparts. CONCLUSIONS: The differences in reproductive parameters between the two genetically very similar populations could not be explained by possible confounders and may be due to unknown environmental or lifestyle-related factors.

Risk factors for developing systemic lupus erythematosus: a case-control study in southern Sweden.

OBJECTIVE: To explore the risk factors that have been suggested to be associated with the development of SLE. METHODS: A case-control study was performed and a questionnaire was developed to obtain the data. Consecutive female incident cases diagnosed between 1981 and 1999 in a defined geographical area in southern Sweden were included. Controls, matched for calendar year of birth, were selected randomly from the same area. In total, 85 cases and 205 controls agreed to participate. The questionnaire included questions about formal education, body weight and height, medical history, family history of autoimmune diseases, exposure to ultraviolet radiation, animals, hair-colouring dyes, alfalfa (lucerne) sprouts, smoking and alcohol habits, history of physical traumata, blood transfusion, silicone breast implants, exogenous oestrogens, other medication, and significant negative life events. RESULTS: Using a multivariate model, a history of hypertension [odds ratio (OR)=3.7, 95% confidence interval (CI) 1.4-9.8], drug allergy (OR=3.6, 95% CI 1.4-9.5), a type I/II sun-reactive skin type (OR=2.3, 95% CI 1.1-4.8) and a family history of SLE (OR=6.8, 95% CI 1.4-32) were all significantly associated with an increased risk of developing SLE, whereas consumption of alcohol was inversely associated with the risk of SLE (use of alcohol very seldom, OR=1.0; 1-150 g/month, OR=0.4, 95% CI 0.2-1.0; >150 g/month, OR=0.2, 95% CI 0.1-0.5). A suggested association with increased SLE risk was seen for smoking (OR=1.8, 95% CI 0.9-3.6) and blood transfusions (OR=2.3, 95% CI 0.9-5.8). Neither exposure to exogenous oestrogen nor exposure to hair-colouring dyes was associated with SLE. CONCLUSIONS: Risk factors of both exogenous and endogenous origin were identified in this population-based series of SLE patients.

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.

Polychlorinated biphenyls in blood plasma among Swedish female fish consumers in relation to time to pregnancy.

The purpose of this study was to assess the association between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma, a biomarker of exposure to polychlorinated biphenyls (PCB), and time to pregnancy (TTP) in a group of women with a varying dietary exposure to PCB. For 121 Swedish east coast fishermen's wives (median year of birth 1956, range 1945-1968), information on selt-reported TTP for the first planned pregnancy (median 2 mo, range 0-48) and CB-153 concentrations from blood samples drawn in 1995 (median 144 ng/g lipid, range 16-566) were available. Each woman's CB-153 concentration in plasma at the time immediately preceding her pregnancy was estimated, taking into account reduction of body burden of CB-153 due to lactation, the yearly reduction of PCB in Baltic Sea fish, as well as the biological half-life of CB-153. Based on the estimated CB-153 concentrations, subjects were categorized into tertiles as low (37-206 ng/g lipid), medium (207-330 ng/g lipid), and high (331-,1036 ng/g lipid) exposure groups. TTP in the medium- and high-exposure groups were then compared to TTP in the low-exposure group by estimating the corresponding success rate (i.e., the number of pregnancies per person month) ratios (SuRR) using discrete Cox regression, taking into account essential confounders. No obvious association between estimated CB-153 concentration and TTP was observed (medium vs. low: SuRR 0.77 [95% CI 0.47-1.28] and high vs. low: SuRR 0.95 10.74-1.23]). The present data give no support for a negative association between the plasma CB-153 concentrations observed in the present study and TTP. It should, however, be borne in mind that the study group was rather small and mainly included relatively young women, likely to have been only moderately exposed.