Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries

Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965–2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07–1.60] and in the high (RR = 1.41; 95% CI = 1.16–1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34–3.68). The strongest association was found for stomach cancer [RRmedium = 1.17 (95% CI = 0.37–3.70), RRhigh = 3.13 (95% CI = 1.17–8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type

Longitudinal assessment of PCBs and chlorinated pesticides in pregnant women from Western Canada

BACKGROUND: Maternal exposures to organochlorines prior to pregnancy are considered a risk to neonatal welfare, specifically in relation to neurocognitive functions. There is growing interest in the evaluation of maternal blood testing as a marker for fetal exposure as well as the variable geographic distribution of these priority chemicals. METHODS: Three hundred and twenty-three women in the second trimester of pregnancy entered the study at a prenatal clinic providing genetic counselling information. Subjects who had an indication for genetic amniocentesis based on late maternal age were eligible to participate. Two hundred and thirty-eight completed an environmental questionnaire. A sample of amniotic fluid was taken for karyotype analysis in 323 women and blood samples during pregnancy (209), at birth (105) and from the umbilical cord (97) and breast milk (47) were also collected. These samples were tested for 29 PCB congeners and organochlorine pesticides. RESULTS: The concentrations of PCB 153 in these media were relatively low in relation to other studies. Σ PCBs measurements in samples taken during the second trimester of pregnancy, at birth and in the umbilical cord were strongly correlated. Specific measurements of PCB 153 and PCB 180 among those subjects with completed sampling of blood samples from mothers and cord samples were significantly correlated. The concentrations of PCBs and pesticides did not differ in relation to prior spontaneous abortion history. There were no organochlorines present in the amniotic fluid at the current level of quantification. CONCLUSION: Pregnant women from the Western Canada region of Calgary, Alberta are exposed to relatively low concentrations of organochlorines. Measurement of maternal blood during the second trimester of pregnancy can reliably estimate the fetal exposure to PCBs. This estimate is reliable for Group 2 and 3 PCBs as well as PCB 153 and PCB 180. The amniotic fluid does not contain measurable concentrations of pesticides and PCBs under the conditions of the levels of quantification

Allergic conditions and risk of hematological malignancies in adults: a cohort study

BACKGROUND: Two contradictory hypotheses have been proposed to explain the relationship between allergic conditions and malignancies, the immune surveillance hypothesis and the antigenic stimulation hypothesis. The former advocates that allergic conditions may be protective against development of cancer, whereas the latter proposes an increased risk. This relationship has been studied in several case-control studies, but only in a few cohort studies. METHODS: The association between allergic conditions and risk of developing leukemia, Hodgkin's disease, non-Hodgkin's lymphoma and myeloma was investigated in a cohort of 16,539 Swedish twins born 1886–1925. Prospectively collected, self-reported information about allergic conditions such as asthma, hay fever or eczema was obtained through questionnaires administered in 1967. The cohort was followed 1969–99 and cancer incidence was ascertained from the Swedish Cancer Registry. RESULTS: Hives and asthma tended to increase the risk of leukemia (relative risk [RR] = 2.1, 95% Confidence Interval [CI] 1.0–4.5 and RR = 1.6, 95% CI 0.8–3.5, respectively). There was also an indication of an increased risk of non-Hodgkin's lymphoma associated with eczema during childhood (RR = 2.3, 95% CI 1.0–5.3). CONCLUSION: In contrast to most previous studies, our results do not indicate a protective effect of allergic conditions on the risk of developing hematological malignancies. Rather, they suggest that allergic conditions might increase the risk of some hematological malignancies

Reproductive toxicity of seafood contaminants: Prospective comparisons of Swedish east and west coast fishermen's families

Cohorts comprising fishermen's families on the east coast of Sweden have been found to have a high consumption of contaminated fish as well as high body burdens of persistent organochlorine pollutants (POPs). Their west coast correspondents are socio-economically similar, but with considerably lower POP exposure since the fish caught on the west coast is far less contaminated. The rationale for this was that the cohorts residing on the east coast of Sweden have been found to have a high consumption of contaminated fish as well as high body burdens of POPs, whereas their west coast correspondents are socio-economically similar, but with considerably lower POP exposure since the fish caught on the west coast is far less contaminated. Among the reproductive outcomes investigated are included both male and female parameters, as well as couple fertility and effects on the fetus. A range of exposure measures, including both questionnaire assessments of fish consumption and biomarkers, have been used

Determinants of serum concentrations of organochlorine compounds in Swedish pregnant women: a cross-sectional study

BACKGROUND: We performed a cross-sectional study of associations between personal characteristics and lipid-adjusted serum concentrations of certain PCB congeners and chlorinated pesticides/metabolites among 323 pregnant primiparous women from Uppsala County (age 18–41 years) sampled 1996–1999. METHODS: Extensive personal interviews and questionnaires about personal characteristics were performed both during and after pregnancy. Concentrations of organochlorine compounds in serum lipids in late pregnancy were analysed by gas chromatography. Associations between personal characteristics and serum levels of organochlorine compounds were analysed by multiple linear regression. RESULTS: Participation rate was 82% (325 of 395 women). Serum concentrations of PCB congeners IUPAC no. 28, 52, 101, 105 and 167, and o, p'-DDT and -DDE, p, p'-DDT and -DDD, oxychlordane, and γ- and α-HCH were in many cases below the limit of quantification (LOQ). No statistical analysis of associations with personal characteristics could be performed for these substances. Concentrations of PCB congeners IUPAC no. 118, 138, 153, 156 and 180, HCB, β-HCH, trans-nonachlor and p, p'-DDE increased with increased age and were highest in women sampled early during the 4 year study period. This shows that older women and women sampled early in the study had experienced the highest life-time exposure levels, probably mainly during childhood and adolescence. The importance of early exposures was supported by lower PCB concentrations and higher β-HCH and p, p'-DDE concentrations among women born in non-Nordic countries. Moreover, serum concentrations of certain PCBs and pesticide/metabolites were positively associated with consumption of fatty fish during adolescence, and concentrations of CB 156, CB 180 and p, p'-DDE increased significantly with number of months women had been breast-fed during infancy. Short-term changes in bodily constitution may, however, also influence serum concentrations, as suggested by negative associations between concentrations of organochlorine compounds and BMI before pregnancy and weight change during pregnancy. CONCLUSION: Although some of the associations could be caused by unknown personal characteristics confounding the results, our findings suggest that exposures to organochlorine compounds during childhood and adolescence influence the body burdens of the compounds during pregnancy

Spontaneous and radiation-induced chromosomal instability and persistence of chromosome aberrations after radiotherapy in lymphocytes from prostate cancer patients

The aim of the study was to compare the spontaneous and ex vivo radiation-induced chromosomal damage in lymphocytes of untreated prostate cancer patients and age-matched healthy donors, and to evaluate the chromosomal damage, induced by radiotherapy, and its persistence. Blood samples from 102 prostate cancer patients were obtained before radiotherapy to investigate the excess acentric fragments and dicentric chromosomes. In addition, in a subgroup of ten patients, simple exchanges in chromosomes 2 and 4 were evaluated by fluorescent in situ hybridization (FISH), before the onset of therapy, in the middle and at the end of therapy, and 1 year later. Data were compared to blood samples from ten age-matched healthy donors. We found that spontaneous yields of acentric chromosome fragments and simple exchanges were significantly increased in lymphocytes of patients before onset of therapy, indicating chromosomal instability in these patients. Ex vivo radiation-induced aberrations were not significantly increased, indicating proficient repair of radiation-induced DNA double-strand breaks in lymphocytes of these patients. As expected, the yields of dicentric and acentric chromosomes, and the partial yields of simple exchanges, were increased after the onset of therapy. Surprisingly, yields after 1 year were comparable to those directly after radiotherapy, indicating persistence of chromosomal instability over this time. Our results indicate that prostate cancer patients are characterized by increased spontaneous chromosomal instability. This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks. Radiotherapy-induced chromosomal damage persists 1 year after treatment

DNA repair capacity as a possible biomarker of breast cancer risk in female BRCA1 mutation carriers

The BRCA1 gene product helps to maintain genomic integrity through its participation in the cellular response to DNA damage: specifically, the repair of double-stranded DNA breaks. An impaired cellular response to DNA damage is a plausible mechanism whereby BRCA1 mutation carriers are at increased risk of breast cancer. Hence, an individual's capacity to repair DNA may serve as a useful biomarker of breast cancer risk. The overall aim of the current study was to identify a biomarker of DNA repair capacity that could distinguish between BRCA1 mutation carriers and non-carriers. DNA repair capacity was assessed using three validated assays: the single-cell alkaline gel electrophoresis (comet) assay, the micronucleus test, and the enumeration of γ-H2AX nuclear foci. DNA repair capacity of peripheral blood lymphocytes from 25 cancer-free female heterozygous BRCA1 mutation carriers and 25 non-carrier controls was assessed at baseline and following cell exposure to γ – irradiation (2 Gy). We found no significant differences in the mean tail moment, in the number of micronuclei or in the number of γ-H2AX nuclear foci between the carriers and non-carriers at baseline, and following γ-irradiation. These data suggest that these assays are not likely to be useful in the identification of women at a high risk for breast cancer

Menstrual irregularity and bone mass in premenopausal women: Cross-sectional associations with testosterone and SHBG

Background. There have been few studies examining the associations between menstrual irregularity, androgens and bone mass in population-based samples of premenopausal women. This study aimed to describe the associations between menstrual pattern, testosterone, sex hormone binding globulin (SHBG) and bone mass in a population-based sample of premenopausal women. Methods. Cross-sectional study (N = 382, mean age 31.5 years). Menstrual pattern was assessed by questionnaire, bone mass measured by quantitative ultrasound (QUS) and androgen status was assessed by levels of serum testosterone, SHBG and the free androgen index (FAI). Results. Women with irregular cycles (n = 41, 11%) had higher free androgen index (FAI, P = 0.01) and higher QUS measurements including speed of sound (SOS, 1%, P < 0.05), quantitative ultrasound index (QUI, 7%, p < 0.05), and broadband ultrasound attenuation (BUA, 7%, p = 0.10). These associations persisted after adjustment for age and body mass index (BMI). After further adjustment for hormonal factors (either testosterone, SHBG or FAI), the strength of the associations was moderately attenuated, however, women with irregular cycles still had a 6% increase in mean QUS. Total testosterone, FAI and SHBG were also associated with QUS measures (testosterone and FAI, r +0.11 to +0.21, all p < 0.05; SHBG r -0.14 to -0.16, all p < 0.05) and the associations remained significant after adjustment. Conclusion. Irregular menstrual cycles were associated with higher bone mass in this population-based sample of premenopausal women suggesting menstrual disturbance should continue to be evaluated but may be less harmful for bone mass. The association between menstrual irregularity and bone mass was partially mediated by markers of androgen status especially free testosterone