Department of Epidemiology Research, Statens Serum Institut, Department of Occupational and Environmental Medicine, Bispebjerg Hospital and Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.Department of Epidemiology Research, Statens Serum Institut, Department of Occupational and Environmental Medicine, Bispebjerg Hospital and Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. firstname.lastname@example.org.
This study assessed the suggested association between pregnancy-associated hypertensive disorders, hyperemesis and subsequent risk of RA using a cohort with information about pre-pregnancy health.
Self-reported information on pre-pregnancy health, pregnancy course, gestational hypertension, pre-eclampsia and hyperemesis was available from 55 752 pregnant women included in the Danish National Birth Cohort. Information about pregnancy-related factors and lifestyle was obtained by interviews twice during pregnancy and at 6 months post-partum. Women were followed for RA hospitalizations identified in the Danish National Patient Register. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards models. Women with RA and non-specific musculoskeletal problems at the time of pregnancy were excluded.
On average, women were followed for 11 years after childbirth and 169 cases of RA were identified. The risk of RA was increased in women with pre-eclampsia (n = 11, HR = 1.96, 95% CI 1.06, 3.63), a poor self-rated pregnancy course (n = 32, HR = 1.63, 95% CI 1.11, 2.39) and fair or poor self-rated pre-pregnancy health (fair health: n = 86, HR = 1.52, 95% CI 1.11, 2.09; poor health: n = 14, HR = 3.24, 95% CI 1.82, 5.76). Hyperemesis was not associated with risk of RA.
We confirmed the previously suggested increased risk of RA in women with pre-eclampsia and also found an inverse association between self-rated pre-pregnancy health and risk of RA. These results suggest that the clinical onset of RA is preceded by a prolonged subclinical phase that may interfere with women's general well-being and pregnancy course or that some women carry a shared predisposition to pre-eclampsia and RA.
Department of Environmental Chemistry, NILU - Norwegian Institute for Air Research, Fram Centre, Hjalmar Johansens Gate 14, NO-9296 Tromsø, Norway; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Sykehusveien 44, NO-9037 Tromsø, Norway; Department of Laboratory Medicine, Diagnostic Clinic, University Hospital of North Norway, Sykehusveien 38, NO-9038 Tromsø, Norway. Electronic address: email@example.com.
Longitudinal biomonitoring studies can provide unique information on how human concentrations change over time, but have so far not been conducted for per- and polyfluoroalkyl substances (PFASs) in a background exposed population.
The objectives of this study were to determine: i) serum PFAS time trends on an individual level; ii) relative compositions and correlations between different PFASs; and iii) assess selected PFAS concentrations with respect to periodic (calendar year), age and birth cohort (APC) effects.
Serum was sampled from the same 53 men in 1979, 1986, 1994, 2001 and 2007 in Northern Norway and analysed for 10 PFASs. APC effects were assessed by graphical and mixed effect analyses.
The median concentrations of perfluorooctane sulphonic acid (PFOS) and perfluorooctanoic acid (PFOA) increased five-fold from 1979 to 2001 and decreased by 26% and 23%, respectively, from 2001 to 2007. The concentrations of PFOS and PFOA peaked during 1994-2001 and 2001, respectively, whereas perfluorohexane sulphonic acid (PFHxS) increased to 2001, but did not demonstrate a decrease between 2001 and 2007. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) displayed increasing trends throughout the entire study period (1979-2007). Although PFOS comprised dominating and stable proportions of PFAS burdens during these years, the contributions from PFOA and PFHxS were considerable. The evaluation of APC effects demonstrated that calendar year was the dominating influence on concentrations of PFOA, PFUnDA, and PFOS, although time-variant and weaker associations with age/birth cohort were indicated.
The concentration changes of 10 PFASs in the repeated measurements from 1979 to 2007 demonstrated divergent time trends between the different PFASs. The temporal trends of PFASs in human serum during these 30years reflect the overall trends in historic production and use, although global transport mechanisms and bioaccumulation potential of the different PFASs together with a varying extent of consumer exposure influenced the observed trends. Sampling year was the strongest descriptor of PFOA, PFUnDA and PFOS concentrations, and the calendar-year trends were apparent for all birth year quartiles. Discrepancies between the trends in this current longitudinal study and previous cross-sectional studies were observed and presumably reflect the different study designs and population characteristics.
Affiliations of authors: Cancer Prevention Program (ARK) and SWOG Statistical Center (AKD, CMT, PJG), Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Epidemiology (ARK, GEG) and Department of Environmental Health (GEG), University of Washington, Seattle, WA; University of Missouri, Research Reactor Center, Columbia, MO (JSM); Harry S. Truman Memorial Veterans Hospital, Columbia, MO (JSM); Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX (IMT); Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA (FLM); Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (LMM, HLP); Moores Cancer Center, University of California San Diego, San Diego, CA (SML); Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH (EAK).
The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This case-cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status.
There were 1739 total and 489 high-grade (Gleason 7-10) PCa cases and 3117 men in the randomly selected cohort. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of supplementation within quintiles of baseline toenail selenium. Cox proportional hazards models were used to estimate hazard ratios, and all statistical tests are two-sided.
Toenail selenium, in the absence of supplementation, was not associated with PCa risk. Selenium supplementation (combined selenium only and selenium + vitamin E arms) had no effect among men with low selenium status (
Comment In: J Natl Cancer Inst. 2014 Mar;106(3):dju00524563520
Perfluoroalkyl substances (PFAS) are persistent and ubiquitous environmental contaminants, and human exposure to these substances may be related to preeclampsia, a common pregnancy complication. Previous studies have found serum concentrations of PFAS to be positively associated with pregnancy-induced hypertension and preeclampsia in a population with high levels of exposure to perfluorooctanoate. Whether this association exists among pregnant women with background levels of PFAS exposure is unknown. Using data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health, we carried out a study of nulliparous pregnant women enrolled in 2003-2007 (466 cases, 510 noncases) to estimate associations between PFAS concentrations and an independently validated diagnosis of preeclampsia. We measured levels of 9 PFAS in maternal plasma extracted midpregnancy; statistical analyses were restricted to 7 PFAS that were quantifiable in more than 50% of samples. In proportional hazards models adjusted for maternal age, prepregnancy body mass index (weight (kg)/height (m)(2)), educational level, and smoking status, we observed no strongly positive associations between PFAS levels and preeclampsia. We found an inverse association between preeclampsia and the highest quartile of perfluoroundecanoic acid concentration relative to the lowest quartile (hazard ratio = 0.55, 95% confidence interval: 0.38, 0.81). Overall, our findings do not support an increased risk of preeclampsia among nulliparous Norwegian women with background levels of PFAS exposure.
This study attempts to construct valid indices for mechanical exposure of the shoulder-neck region with relation to the development of shoulder-neck pain in a 1-year perspective study of a general population.
A comprehensive questionnaire was presented to 14 556 subjects aged 45 or 65 years and repeated after 12 months. Twenty-four questions concerning positions, movements, and manual materials handling were registered on a 3-point impact scale. Musculoskeletal problems were reported on a slightly modified version of the Standardized Nordic Questionnaire for the Analysis of Musculoskeletal Symptoms. Test-retest stability after 2 weeks was calculated for 232 consecutive participants. Based on mechanistic theories, 4 exposure indices were formed. Another 5 constructs were obtained by factor analysis.
All the indices showed good test-retest stability, and 5 of them had very good internal consistency. Due to overlaps between the indices, 2 indices stood out as having unique properties. One of them concerned mainly postures and the other dealt primarily with measured lifting. However, the latter was not related to the shoulder-neck pain outcome when adjusted for the posture index. The posture index showed an exposure-effect relationship with the outcome. The job titles implied a large degree of exposure misclassification.
The posture index is recommended as a mechanical exposure index for analyses of interaction with other possible determinants of shoulder-neck pain (ie, psychosocial factors). The use of such an index instead of job titles in large population studies will reduce the risk of misclassification.
Leptin is involved in the regulation of body weight, but the relative role of genetic and environmental influences on inter-individual variation in leptin levels is unknown.
To investigate the genetic and environmental contributions to the association of body mass index (BMI) with serum leptin levels, 58 monozygotic (MZ, 27M, 31F), and 74 like-sexed dizygotic (DZ, 32M, 42F) Finnish twin pairs aged 50--76 y were studied.
Serum leptin levels, weight, height, hip and waist measurements.
Women had higher mean leptin levels (16.8+/-9.5 ng/ml), and more overall variability in leptin levels than men (6.4+/-3.5 ng/ml; P
It has been suggested that main risk factors for development of allergic diseases operate already during pregnancy and in early childhood.
To study the association between gestational age, birth weight, parity and parental farming with the risk of atopy and asthma in young adults.
In a prospective birth cohort study, 5192 subjects born in Northern Finland in 1966 were followed up at the age of 31. Skin prick tests were done to three of the most common allergens in Finland and to house dust mite. Data on doctor-diagnosed asthma was obtained from questionnaires. Perinatal data had already been collected during pregnancy.
The risk of atopy increased linearly with increasing length of pregnancy among babies born in the 35th weak of gestation or later. Gestational age equal to, or over 40 weeks compared with less than 36 weeks was associated with an increased risk of atopy (multivariate odds ratio 1.65, 95% CI 1.16, 2.34). The association was stronger among farmers' children (P for interaction 0.01). High parity and being a farmer's child (multivariate odds ratio 0.50, 95% CI 0.42-0.60) was associated with decreased risk of atopy. In contrast, no associations were observed for doctor-diagnosed asthma.
The results underline the importance of pregnancy and very early childhood in the development of atopy, and suggest that timing of the environmental exposure is of importance for the immune system. No association was observed for asthma, which may be due to the multifactorial origins of asthma.
This study examined the change in heritability of adult body height across birth cohorts in Finland.
In 1981, cross-sectional questionnaires were completed by 10,968 twin pairs born before 1958. The effect of genetic factors was estimated via genetic modeling.
Heritability increased from the cohort born before 1929 (0.76, 95% confidence interval [CI] = 0.65, 0.88 in men; 0.66, 95% CI = 0.55, 0.77 in women) to that born in 1947 through 1957 (0.81, 95% CI = 0.73, 0.87 in men; 0.82, 95% CI = 0.75, 0.89 in women).
Heritability of height increased across Finnish birth cohorts born in the first half of this century and leveled off after World War II. Environmental factors, compared with genetic factors, appear to be more important among women than men.
OBJECTIVE: To investigate the association between metabolic syndrome and some of its components with the incidence of cataract extraction. DESIGN: Population-based prospective cohort study. PARTICIPANTS: A total of 35,369 women, participating in the Swedish Mammography Cohort, aged 49 to 83 years, who completed a self-administered questionnaire about anthropometric measurements and lifestyle factors in 1997. METHODS: The women were followed from September of 1997 to October of 2005. The cohort was matched with registers of cataract extraction in the study area. MAIN OUTCOME MEASURES: Incident surgical extraction of age-related cataract. RESULTS: We identified 4508 incident cases of cataract extractions during 98 months of follow-up. In multivariate analysis, women with a waist circumference >or=80 cm had an 8% increased risk of cataract extraction (rate ratio [RR], 1.08; 95% confidence interval [CI], 0.99-1.17). Women with diabetes had a 43% increased risk of cataract extraction (RR, 1.43; 95% CI, 1.10-1.86), and hypertension was associated with a 12% increased risk (RR, 1.12; 95% CI, 0.99-1.26). Women with all 3 components of the metabolic syndrome (waist >or=80 cm, diabetes, and hypertension) had a 68% increased risk of cataract extraction (RR, 1.68; 95% CI, 1.40-2.02) compared with women without any of these components. Among women aged less than 65 years at baseline with all 3 components of metabolic syndrome, the risk of cataract extraction was approximately 3-fold more (RR, 2.80; CI, 1.94-4.03). CONCLUSIONS: Metabolic syndrome and its components, abdominal adiposity, diabetes, and hypertension, seem to be associated with an increased risk for cataract extraction, especially among women aged less than 65 years.
PURPOSE: To investigate whether blue-collar employment in the Swedish rubber industry from 1973 onwards had a negative impact on reproductive health. METHODS: Pairs of mother and child, and triads of father-mother-child were obtained through linkage of a cohort of 18,518 rubber factory employees with the Swedish Population Registry. Birth outcomes were obtained from the Medical Birth Register for 17,918 children. For each child, parental employment as blue-collar rubber worker during the pregnancy and sperm maturation period was obtained from work-place records. Children to female food industry workers, in all 33,256, constituted an external reference group. RESULTS: The sex ratio was reversed, with odds ratio (OR) for having a girl was 1.15 (95% CI 1.02, 1.31) when the mother was exposed. When both parents were exposed, the OR was even higher, 1.28 (95% CI 1.02, 1.62). An increased risk of multiple births was observed when both parents were exposed, with OR 2.42 (95% CI 1.17, 5.01). Children with both maternal and paternal exposure had a reduced birth weight compared to the external reference cohort. After adjustment for smoking (available for births from 1983 onwards), ethnicity and sex, the difference between children (singletons, live births) with maternal and paternal exposure and external referents was -142 g (95% CI -229, -54). The adjusted OR for having a small-for-gestational-age child was 2.15 (95% CI 1.45, 3.18) when the mother was a rubber worker during the pregnancy. CONCLUSION: There were clear indications that reproductive outcome was adversely affected in rubber workers. The findings warrant further investigation with refinement of exposure indices and inclusion of other endpoints of reproductive health.
BACKGROUND: In many countries, a general shortage of nurses is a public health problem, and retention of nurses in active work is a challenge. The aim of this study was to ascertain whether the same individual factors, working conditions and health problems had led to increased probability of both leaving jobs and prolonged sickness absence in a cohort of Swedish nurses over a period of 3 years. METHODS: A baseline questionnaire was answered by 2293 nurses, representing a response rate of 86%. Exposed and unexposed nurses were compared with regard to two outcomes. During the 3-year follow-up, exposed and unexposed nurses were compared with regard to two outcomes: resigning and having at least one sick leave spell that lasted 28 days or longer. RESULTS: We found that 18% of the nurses left their employment, and 16% had sick leave spells > or =28 days. Work in geriatric care, being socially excluded by superiors and/or workmates, negative effects of organizational changes and poor self-rated general health were factors that increased the likelihood of both leaving jobs and long-term sick leave. CONCLUSIONS: The present results underline the importance of improving working conditions and supporting sustainable health in order to prevent high turnover and prolonged sick leave among nurses. Resigning and moving to another institution can be interpreted as a way to actively cope with an unhealthy work environment.
In 2002 authors initiated a US-Ukraine collaborative study on bronchial asthma among 2177 6-8 year old children who resided in Kyiv, Dniprodzerzhinsk and Mariupol, Ukraine in 2002 and who were participants in the Family and Children of Ukraine Longitudinal Cohort Study. The overall goal of the study is to investigate the epidemiology and risk factors for asthma and asthma--related symptoms among these children. The study design comprises of three phases. During the first phase Questionnaires including the International Study of Asthma and Allergies in Childhood (ISAAC) core module on wheeze, as well as questions about other respiratory symptoms (including night cough and phlegm) were given to parents of 2177 children aged 6-8 years. The authors examined the prevalence of wheezing and dry cough at night not associated with colds during the past year among the surveyed children. The parent-reported prevalence of wheezing was significantly different among these three Ukrainian cities: 14.4% in Kyiv, 19% in Mariupol and 5.7% in Dniprodzerzhinsk. The prevalence of dry cough at night not associated with colds was also different in Kyiv, Mariupol and Dniprodzerzhinsk and was 11.4%, 6.9% and 6.9% respectively). The authors conclude that the prevalence of wheezing illness and dry cough at night not associated with colds during the past year varies among Ukrainian cities with the highest prevalence in kyiv, the most "westernized" of these cities.
Acrylamide, a probable human carcinogen, is formed in several foods during high-temperature processing. So far, epidemiological studies have not shown any association between human cancer risk and dietary exposure to acrylamide. The purpose of this study was to conduct a nested case control study within a prospective cohort study on the association between breast cancer and exposure to acrylamide using biomarkers. N-terminal hemoglobin adduct levels of acrylamide and its genotoxic metabolite, glycidamide in red blood cells were analyzed (by LC/MS/MS) as biomarkers of exposure on 374 breast cancer cases and 374 controls from a cohort of postmenopausal women. The adduct levels of acrylamide and glycidamide were similar in cases and controls, with smokers having much higher levels (approximately 3 times) than nonsmokers. No association was seen between acrylamide-hemoglobin levels and breast cancer risk neither unadjusted nor adjusted for the potential confounders HRT duration, parity, BMI, alcohol intake and education. After adjustment for smoking behavior, however, a positive association was seen between acrylamide-hemoglobin levels and estrogen receptor positive breast cancer with an estimated incidence rate ratio (95% CI) of 2.7 (1.1-6.6) per 10-fold increase in acrylamide-hemoglobin level. A weak association between glycidamide hemoglobin levels and incidence of estrogen receptor positive breast cancer was also found, this association, however, entirely disappeared when acrylamide and glycidamide hemoglobin levels were mutually adjusted.
BACKGROUND/OBJECTIVES: Milk and dairy products are the main sources of iodine in the Norwegian diet. This is due to a high consumption of milk and dairy products combined with a relatively high concentration of iodine in milk because of mandatory iodine fortification of cow fodder. The aim of the present study was to investigate the relation between 24-h urinary iodine excretion and estimated dietary intake, and to explore the use of 24-h urinary iodine excretion as a possible biomarker for the intake of milk and dairy products when assessing the validity of a new food frequency questionnaire for pregnant women participating the Norwegian Mother and Child Cohort Study (MoBa). SUBJECT/METHODS: 119 women participated in a validation study. Iodine was analyzed in 24-h urine. Dietary intakes were estimated by a food frequency questionnaire (FFQ) and a 4-day weighed food diary (FD). Using linear regression, predictors of urinary iodine excretion were identified. The triangular method was applied to calculate validity coefficients. RESULTS: Significant predictors of 24-h urinary iodine excretion were: intake of dairy products, iodine-containing supplements and intake of fruit/vegetables. Fish/seafood intake and time of the year influenced 24-h urinary iodine excretion, although not significantly. The validity coefficients observed for total intake of dairy products were 0.65, 0.94 and 0.52 for the FFQ, the FD and the 24-h urinary iodine excretion, respectively. CONCLUSIONS: The present study showed that 24-h urinary iodine excretion may be a useful biomarker for validating the intake of milk and dairy products in pregnant Norwegian women.
BACKGROUND: Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are man-made, persistent organic pollutants widely spread throughout the environment and human populations. They have been found to interfere with fetal growth in some animal models, but whether a similar effect is seen in humans is uncertain. OBJECTIVES: We investigated the association between plasma levels of PFOS and PFOA in pregnant women and their infants' birth weight and length of gestation. METHODS: We randomly selected 1,400 women and their infants from the Danish National Birth Cohort among those who completed all four computer-assisted telephone interviews, provided the first blood samples between gestational weeks 4 and 14, and who gave birth to a single live-born child without congenital malformation. PFOS and PFOA were measured by high performance liquid chromatography-tandem mass spectrometer. RESULTS: PFOS and PFOA levels in maternal plasma were on average 35.3 and 5.6 ng/mL, respectively. Only PFOA levels were inversely associated with birth weight (adjusted beta = -10.63 g; 95% confidence interval, -20.79 to -0.47 g). Neither maternal PFOS nor PFOA levels were consistently associated with the risk for preterm birth or low birth weight. We observed no adverse effects for maternal PFOS or PFOA levels on small for gestational age. CONCLUSION: Our nationwide cohort data suggest an inverse association between maternal plasma PFOA levels and birth weight. Because of widespread exposure to these chemicals, our findings may be of potential public health concern.
Comment In: Environ Health Perspect. 2007 Nov;115(11):A528-918007963
Comment In: Environ Health Perspect. 2008 Jul;116(7):A284; author reply A284-A28518629333
BACKGROUND. In addition to their value in assessing pulmonary health and disease, spirometric variables have been shown to be powerful predictors of time until death in aging populations. The sources of variability in these spirometric values are consequently of relevance to basic gerontological research, and also of potential value in clinical application. The objective of this study was to estimate genetic and environmental sources of variance in pulmonary function. METHODS. The study involved 230 Swedish twin pairs (mean age = 64.9 years), of which number 37 monozygotic (MZ) pairs and 72 dizygotic (DZ) pairs had been separated and reared apart. Comparing these groups to the 57 MZ and 64 DZ pairs reared together permits stronger interpretation than that of conventional twin studies. Measures of vital capacity (VC) and forced expiratory volume in one second (FEV1) were residualized for height, age, sex, and tobacco consumption in pack-years. RESULTS. Maximum likelihood analyses of VC and FEV1 gave heritability estimates of .48 and .67, respectively. Age effects were explored both by dividing the sample into two cohorts, respectively above and below 65 years, and by moving interval analysis. In the two-cohort analysis, heritabilities were somewhat higher for the older cohort than the younger cohort for FEV1. The opposite was true for VC: heritability was lower in the older cohort, and there was evidence for a shared rearing environmental effect for this group. Moving interval analysis suggests these differences are gradual rather than saltatory. There were no gender differences in parameter estimates. CONCLUSION. Genetic factors account for between one-half and two-thirds of the variability in pulmonary function. There is a suggestion of age differences in the relative importance of genetic and environmental influences.
OBJECTIVE: To follow up cancer incidence and mortality in a group of Swedish battery workers exposed to nickel hydroxide and cadmium oxide. METHODS: 869 workers, employed at least one year between the years 1940 and 1980 were followed up until 1992. Vital status and causes of death were obtained from the Swedish cause of death registry. Cancer morbidity was retrieved from the Swedish cancer registry. Regional reference rates were used to compute the expected numbers of deaths and cancers. RESULTS: Up to 31 December, 1992, a total of 315 deaths (292 in men and 23 in women) had occurred in the cohort. For men, the overall standardised mortality ratio (SMR) was 106 (95% confidence interval (95% CI) 93.7 to 118) and for women 83.8 (95% CI 53.1 to 126). The SMRs for total cancer mortality were 125 (95% CI 98.2 to 157) for men and 69.5 (95% CI 25.5 to 151) for women. The SMR for lung cancer in men was 176 (95% CI 101 to 287). No lung cancers were found among female workers. Up to 31 December, 1991, a total of 118 cancers had occurred in the cohort. A significantly increased standardised incidence ratio (SIR) was found for cancer of the nose and nasal sinuses in men, three cases v 0.36 expected, yielding an SIR of 832 (95% CI 172 to 2430). Applying a 10 year latency period in cohort members exposed to > or = 1000 micrograms cadmium/m3, the SIR was 1107 (95% CI 134 to 4000). Similarly, for cohort members exposed to 2000 micrograms nickel/m3, the SIR was 1080 (95% CI 131 to 3900). CONCLUSION: There was an increased overall risk for lung cancer, but no exposure-response relation between cumulative exposure to cadmium or nickel and risk of lung cancer. There was a highly significant increased risk of cancer of the nose and nasal sinuses, which may be caused by exposure to nickel or cadmium or a combination of both exposures.
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.
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.