A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function.

The lung surfactant (LS) lining is a thin liquid film covering the air-liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses--neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols--as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose--and albumin known to impair lung functionality by inhibiting LS function.

A multisite randomized controlled trial on time to self-support among sickness absence beneficiaries. The Danish national return-to-work programme.

BACKGROUND: In 2010, the Danish Government launched the Danish national return-to-work (RTW) programme to reduce sickness absence and promote labour market attainment. Multidisciplinary teams delivered the RTW programme, which comprised a coordinated, tailored and multidisciplinary effort (CTM) for sickness absence beneficiaries at high risk for exclusion from the labour market. The aim of this article was to evaluate the effectiveness of the RTW programme on self-support. METHODS: Beneficiaries from three municipalities (denoted M1, M2 and M3) participated in a randomized controlled trial. We randomly assigned beneficiaries to CTM (M1: n = 598; M2: n = 459; M3: n = 331) or to ordinary sickness absence management (OSM) (M1: n = 393; M2: n = 324; M3: n = 95). We used the Cox proportional hazards model to estimate hazard ratios (HR) comparing rates of becoming self-supporting between beneficiaries receiving CTM and OSM. RESULTS: In M2, beneficiaries from employment receiving CTM became self-supporting faster compared with beneficiaries receiving OSM (HR = 1.32, 95% CI: 1.08-1.61). In M3, beneficiaries receiving CTM became self-supporting slower than beneficiaries receiving OSM (HR = 0.72, 95% CI: 0.54-0.95). In M1, we found no difference between the two groups (HR = 0.99, 95% CI: 0.84-1.17). CONCLUSION: The effect of the CTM programme on return to self-support differed substantially across the three participating municipalities. Thus, generalizing the study results to other Danish municipalities is not warranted. TRIAL REGISTRATION: ISRCTN43004323.

Influence of lifestyle factors on long-term sickness absence among female healthcare workers: a prospective cohort study.

BACKGROUND: While previous research has indicated that unhealthy lifestyle is associated with sickness absence, this association may be confounded by occupational class. To avoid this potential confounding, we examined the association between lifestyle factors (smoking, leisure-time physical activity and body mass index) and the occurrence of long-term sickness absence (LTSA; more than three consecutive weeks of registered sickness absence) within a cohort of female health care workers. METHODS: A total of 7401 employees filled out a questionnaire about their health behaviour and work environment. Subsequently, they were followed for 12 months in a national register on social transfer payments (DREAM register). Cox's regression analyses, applied to grouped survival data, were used to estimate the prospective association between these lifestyle factors and LTSA. RESULTS: We found significant associations between all three lifestyle factors and risk of LTSA. The strongest lifestyle factor was current smoking, which increased the risk of LTSA by 35% (95% CI: 1.17-1.54) compared to non- smokers. For body mass index, the risk of LTSA increased with the distance away from 18.5 kg/m2 in either direction (below 18.5 kg/m2: HR: 1.32 per kg/m2; 95% CI. 1.06-1.66; above 18.5 kg/m2: HR: 1.04 per kg/m2; 95% CI: 1.03-1.05). In other words, the more underweight or overweight the women were, the higher the risk of LTSA. A dose-response relationship was found between LTSA and leisure-time physical activity (trend test p-value = 0.01), so that increasing physical activity results in decreasing risk of LTSA. CONCLUSION: In female healthcare workers, an unhealthy lifestyle (too high/ too low body mass index, smoking, and low physical activity) is associated with higher risk of LTSA.

Physical activity and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

The evidence concerning the possible association between physical activity and the risk of prostate cancer is inconsistent and additional data are needed. We examined the association between risk of prostate cancer and physical activity at work and in leisure time in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In our study, including 127,923 men aged 20-97 years from 8 European countries, 2,458 cases of prostate cancer were identified during 8.5 years of followup. Using the Cox proportional hazards model, we investigated the associations between prostate cancer incidence rate and occupational activity and leisure time activity in terms of participation in sports, cycling, walking and gardening; a metabolic equivalent (MET) score based on weekly time spent on the 4 activities; and a physical activity index. MET hours per week of leisure time activity, higher score in the physical activity index, participation in any of the 4 leisure time activities, and the number of leisure time activities in which the participants were active were not associated with prostate cancer incidence. However, higher level of occupational physical activity was associated with lower risk of advanced stage prostate cancer (p(trend) = 0.024). In conclusion, our data support the hypothesis of an inverse association between advanced prostate cancer risk and occupational physical activity, but we found no support for an association between prostate cancer risk and leisure time physical activity.

Prediction of 222Rn in Danish dwellings using geology and house construction information from central databases.

A linear regression model has been developed for the prediction of indoor (222)Rn in Danish houses. The model provides proxy radon concentrations for about 21,000 houses in a Danish case-control study on the possible association between residential radon and childhood cancer (primarily leukaemia). The model was calibrated against radon measurements in 3116 houses. An independent dataset with 788 house measurements was used for model performance assessment. The model includes nine explanatory variables, of which the most important ones are house type and geology. All explanatory variables are available from central databases. The model was fitted to log-transformed radon concentrations and it has an R(2) of 40%. The uncertainty associated with individual predictions of (untransformed) radon concentrations is about a factor of 2.0 (one standard deviation). The comparison with the independent test data shows that the model makes sound predictions and that errors of radon predictions are only weakly correlated with the estimates themselves (R(2) = 10%).

Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide.

We investigated toxicity of 2-3 layered >1 µm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 µg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.

Psychoeducational intervention for patients with cutaneous malignant melanoma: a replication study.

PURPOSE: In 1993, a randomized intervention study among patients with malignant melanoma showed a significant decrease in psychological distress and increased coping capacity 6 months after the intervention and enhanced survival 6 years later. We applied a similar intervention with a few modifications in a randomized controlled trial among Danish patients with malignant melanoma and evaluated results on immediate and long-term effects on psychological distress and coping capacity. PATIENTS AND METHODS: A total of 262 patients with primary cutaneous malignant melanoma were randomly assigned to the control or intervention group. Patients in the intervention group were offered six weekly sessions of 2 hours of psychoeducation, consisting of health education, enhancement of problem-solving skills, stress management, and psychological support. The participants were assessed at baseline before random assignment and 6 and 12 months after surgery. The analyses of the main effects of the intervention were based on analyses of covariance. RESULTS: The patients in the intervention group showed significantly less fatigue, greater vigor, and lower total mood disturbance compared with the controls, and they used significantly more active-behavioral and active-cognitive coping than the patients in the control group. The improvements were only significant at first follow-up. CONCLUSION: The findings of this study support the results of an earlier intervention study among patients with malignant melanoma and indicate that a psychoeducational group intervention for such patients can decrease psychological distress and enhance effective coping. However, this effect is short term and the clinical relevance is not obvious.

Intake of macronutrients as predictors of 5-y changes in waist circumference.

BACKGROUND: The diet may influence the development of abdominal obesity, but the few studies that have prospectively examined the relations between diet and changes in waist circumference (WC) have given inconsistent results. OBJECTIVE: Associations between total energy intake, energy intake from macronutrients, and energy intake from macronutrient subgroups based on different food sources and 5-y differences in WC (DWC) were investigated. DESIGN: A Danish cohort of 22 570 women and 20 126 men aged 50-64 y with baseline data on WC, diet, BMI, and potential confounders reported their WC 5 y later. Associations of baseline diet with DWC were assessed by multiple linear regression analysis. RESULTS: Neither total energy intake nor energy intake from each of the macronutrients was associated with DWC, except for an inverse association with protein, especially animal protein. In women, positive associations with DWC were seen for carbohydrate from refined grains and potatoes and from foods with simple sugars, whereas carbohydrate from fruit and vegetables was inversely associated and significantly different from any other carbohydrate subgroup. The results for men resembled those for women, although none were significant. Vegetable fat was positively associated with DWC for both men and women in a combined analysis. A U-shaped association between alcohol from wine and DWC was present for both sexes, and alcohol from spirits was positively associated with DWC in women. CONCLUSIONS: Although no significant associations with total energy or energy from fat, carbohydrate, or alcohol were observed, protein intake was inversely related to DWC, and some macronutrient subgroups were significantly associated with DWC.

Emotion work within eldercare and depressive symptoms: A cross-sectional multi-level study assessing the association between externally observed emotion work and self-reported depressive symptoms among Danish eldercare workers.

BACKGROUND: Danish professional caregivers have high rates of depressive symptoms. One proposed cause is exposure to emotion work. However, emotion work is usually measured by self-report which may bias results. OBJECTIVES: The objective of this study was to examine the association of emotion work, externally observed at the workplace, with self-reported depressive symptoms of professional caregivers. DESIGN AND DATA SOURCES: The study was a cross-sectional observational study. Data was collected by 9 observers who assessed emotion work stressors and emotion work resources in 124 individual professional caregivers working in 56 work units across 10 eldercare homes. Emotion work stressors were defined as i) barriers for empathetic care, ii) taxing aggressive events, and iii) taxing non-aggressive events. Emotion work resources were defined as i) meaningful events, and ii) social interactions between professional caregivers and residents. Depressive symptoms were measured by a questionnaire sent to all professional caregivers at the 10 eldercare homes. We constructed two samples for analysis: a) a sample of 95 directly observed professional caregivers with full information on covariates, and b) a sample of 205 observed and non-observed professional caregivers with full information on covariates working in one of the 56 observed work units. METHODS: Using multilevel regression models we analysed associations of individual and work unit averaged levels of emotion work with depressive symptoms among professional caregivers. RESULTS: None of the three emotion work stressors were associated with depressive symptoms. Of the two emotion work resources, a high amount of social interactions between professional caregivers and residents were, contrary to expectations, related to higher levels of depressive symptoms at both the individual level and the work unit averaged level. CONCLUSIONS: The unexpected association between social interactions and depressive symptoms need to be replicated in future studies. These future studies should also investigate whether the association of social interactions and level of depressive symptoms depends on the content of the interactions between professional caregivers and residents.

Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity.

Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54 µg/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (-OH and -COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects.

Urinary hydroxyestrogens and breast cancer risk among postmenopausal women: a prospective study.

BACKGROUND: It has been suggested that a low level of the 2-hydroxyestrogen metabolites (2-OHE) and a high level of 16alpha-hydroxyestrone (16alpha-OHE1) are associated with an enhanced risk of breast cancer. We examined the association between the metabolite levels and breast cancer in a nested case-control study, which also addressed hormone replacement therapy (HRT) and estrogen receptor status of the tumors. METHODS: 24,697 postmenopausal Danish women were enrolled in the "Diet, Cancer and Health" cohort. During follow-up, 426 breast cancer cases were identified and controls were matched by age at diagnosis, baseline age, and HRT use. The concentrations of 2-OHE and 16alpha-OHE1 in spot urine were measured by an enzyme immunoassay. Incidence rate ratios (IRR) and 95% confidence intervals (95% CI) were estimated for total and estrogen receptor-specific breast cancer and were stratified according to HRT use. RESULTS: A higher incidence of estrogen receptor-positive breast cancer with an enhanced 2-OHE level was observed among current HRT users, IRR per doubling = 1.30 (95% CI, 1.02-1.66), whereas no association was seen among nonusers of HRT, IRR per doubling = 1.00 (95% CI, 0.69-1.45). The association between estrogen receptor-positive breast cancer and the 16alpha-OHE1 metabolite level was in the opposite direction but slightly weaker and statistically insignificant. For estrogen receptor-negative breast cancer, no significant associations were seen. CONCLUSIONS: The risk of breast cancer, in particular the estrogen receptor-positive type, was enhanced among postmenopausal women using estradiol-based HRT and among those who had a high 2-OHE concentration.

Hormone therapy and the impact of estrogen intake on the risk of ovarian cancer.

BACKGROUND: The association between menopausal hormone therapy (HT) and risk of ovarian cancer is as yet equivocal, and the effect of estrogen and estrogen-progestogen therapy, specifically the effect of the cumulative hormone intake, is unclear. METHODS: We conducted a nationwide population-based case-control study in Denmark. Cases were women aged 35 to 79 years with incident ovarian cancer diagnosed between January 1, 1995, and May 30, 1999. Controls were frequency age-matched women from the Danish Central Population Register. The analyses included data on 376 cases who have not undergone hysterectomy and 1111 controls. RESULTS: The risk of ovarian cancer in relation to oral HT increased with the cumulative intake of the estrogen component of HT but not with the duration or the cumulative intake of the progestogen component when the 3 variables were mutually adjusted. A simple trend was found such that each additional gram of estrogen was associated with the same relative increase. The odds ratio was constant throughout the range of cumulative intake. After adjustment for established risk factors, the estimated odds ratio per each additional gram of cumulative estrogen was 1.056 (95% confidence interval, 1.003-1.112), corresponding to an odds ratio of 1.31 (95% confidence interval, 1.01-1.70) per 5 g of estrogen. CONCLUSIONS: Oral HT is associated with risk of ovarian cancer in women who have not undergone hysterectomy. Our results imply that the risk increases with cumulative oral estrogen intake but not with duration of HT, indicating that the increased ovarian cancer risk associated with oral HT may be diminished substantially by minimizing the daily dose of estrogen from oral HT.

A multilevel study on the association of observer-assessed working conditions with depressive symptoms among female eldercare workers from 56 work units in 10 care homes in Denmark.

OBJECTIVES: Eldercare workers in Denmark have a higher prevalence of poor psychological health than other occupational groups. We examined the association between working conditions assessed by trained observers and depressive symptoms assessed by self-report in a study of female Danish eldercare workers. METHODS: Working conditions were observed based on action regulation theory and defined as (1) regulation requirements, a workplace resource providing opportunity for decision-making and skill development and (2) barriers for task completion. We examined the associations of individual and work unit averaged working conditions with depressive symptoms in a sample of 95 individually observed eldercare workers. Further, we examined the association of work unit averaged working conditions with depressive symptoms in a sample of 205 care workers, including both observed and non-observed individuals. We used regression models that allowed for correlations within work units and care homes and adjusted these models for demographics, job characteristics and stressful life events. RESULTS: Higher levels of regulation requirements were associated with lower depressive symptoms at the individual level (p=0.04), but not at the workplace level. Barriers were not associated with depressive symptoms at the individual level. At the workplace level, a higher number of qualitatively different barriers (p=0.04) and a higher number of barriers for equipment use (p=0.03) were associated with lower levels of depressive symptoms in the age and cohabitation adjusted model, however statistical significance was lost in the fully adjusted model. CONCLUSIONS: Low level of regulation requirements was associated with a high level of depressive symptoms. The study highlights the importance of examining both individual and workplace levels of working conditions.

Effect of habitual dietary calcium intake on calcium supplementation in 12-14-y-old girls.

BACKGROUND: There is no agreement on how much calcium young girls need for optimal bone mineralization. OBJECTIVE: We evaluated whether the effect of calcium supplementation on whole-body bone mineral accretion depends on habitual calcium intake. DESIGN: This was a randomized, double-blind, placebo-controlled, 1-y calcium intervention study of girls aged 12-14 y selected from a larger group according to habitual calcium intake: subgroup A (n = 60) habitually consumed 1000-1307 mg/d (40th-60th percentile), and subgroup B (n = 53) habitually consumed <713 mg/d (<20th percentile). The girls from each subgroup were randomly assigned to receive either 500 mg Ca/d or placebo. Whole-body bone mineral content (BMC), bone area (BA), bone mineral density (BMD), and BMC adjusted for BA, height, and weight (size-adjusted BMC) were measured at baseline and after 1 y. RESULTS: There was no significant effect modification of baseline habitual calcium intake on the relation between calcium supplementation and height, weight, BMC, size-adjusted BMC, BA, BMD, or alkaline phosphatase. Calcium supplementation had an effect on BMD (0.8%; P = 0.049) and tended to show signs of an effect on size-adjusted BMC (0.5%; P = 0.08). CONCLUSION: A modest effect of calcium supplementation on BMD was shown. However, the effect was independent of habitual calcium intake.

Plasma enterolactone and breast cancer incidence by estrogen receptor status.

The phytoestrogen enterolactone has been hypothesized to prevent breast cancer. Because one of the biological effects of enterolactone is probably estrogenic, it is possible that the preventive effect on breast cancer differs with the estrogen receptor (ER) alpha status of the tumor. The objective of this study was to investigate whether high plasma levels of enterolactone are associated with breast cancer risk and whether the ERalpha status of the tumor influences this relation. The cohort study Diet, Cancer and Health included 29,785 women, ages 50 to 64 years, between 1993 and 1997. Information about diet and life-style factors was obtained by questionnaire, and blood was drawn from each participant. We matched 381 postmenopausal breast cancer cases to 381 controls and analyzed the concentration of enterolactone in plasma with a time-resolved fluoroimmunoassay. Associations between plasma concentrations of enterolactone and breast cancer were analyzed by logistic regression. The incidence rate ratio (IRR) for all breast cancer was 0.93 [95% confidence interval (CI), 0.86-1.01] per 20 nmol/L higher plasma concentration of enterolactone. For ERalpha-positive cancers (n=273) only a weak association was seen (IRR, 0.97; 95% CI, 0.88-1.06), whereas for ERalpha-negative cancers (n = 80; IRR, 0.71; 95% CI, 0.53-0.94) a protective effect was seen per 20 nmol/L higher plasma enterolactone. In accordance with earlier research, we found a tendency toward a lower risk for breast cancer with higher concentrations of enterolactone, which was restricted almost entirely to ERalpha-negative breast cancer.

Childhood tumor risk after treatment with ovulation-stimulating drugs.

OBJECTIVE: To assess childhood cancer risk among children conceived following the use of ovulation-stimulating drugs. DESIGN: Record linkage study. SETTING: Infertility patients and their offspring as identified through medical records. PATIENT(S): Cohort of 30,364 Danish women evaluated for infertility beginning in the early 1960s. MAIN OUTCOME MEASURE(S): Standardized incidence ratios (SIRs) compared cancer incidence in the children to the Danish population. Case-cohort techniques calculated rate ratios (RRs) according to prior maternal drug exposures. RESULT(S): A total of 51 cancers were identified among the study children, resulting in an SIR of 1.14 (95% confidence interval [CI] 0.8-1.5). Usage of any fertility drug was associated with an RR of 0.82 (95% CI 0.4-1.6) and clomiphene citrate with an RR of 0.77 (95% CI 0.4-1.6). Tumors occurring early in life and nonhematopoietic malignancies (including neuroblastomas) were not associated with drug usage. Nonsignificant elevations in the risk of cancers occurring later in life, especially childhood hematopoietic malignancies (RR for use of any ovulation-stimulating drugs of 2.30, 95% CI 0.8-6.6), may have been related to underlying reasons for medication usage. CONCLUSION(S): Although the findings of this study are reassuring, additional adequately powered studies should continue monitoring the effects of ovulation-stimulating drugs on specific tumors, including hematopoietic malignancies.

Determinants for non-use of contraception at first intercourse; a study of 10841 young Danish women from the general population.

Based on interview data from 10841 Danish women aged 20 to 29 years, determinants for non-use of contraception at first intercourse (NU) were studied. One-fourth of the women (n = 2704) reported NU, whereas condoms and oral contraceptives were used by, respectively, 59% and 15%. NU decreased with the birth year of the first male partner (OR = 3.6; 95% CI: 2.8-4.8 for or=17 years) at the expense of both oral contraception and condom use. Finally, NU was found to predict high-risk sexual behavior in terms of subsequent multiple sex partners, non-use of condoms, and induced abortion.

Two regions in chromosome 19q13.2-3 are associated with risk of lung cancer.

Lung cancer is the most common fatal cancer among Danish men, and the incidence rate is increasing among women. In a case-cohort study, we have investigated the occurrence of lung cancer in relation to a high-risk haplotype, previously identified for breast cancer among post-menopausal women, and in relation to the closely linked polymorphisms XPD Asp312Asn and Lys751Gln. Among 54220 members of a Danish prospective cohort study aged 50-64 at entry, 265 lung cancer cases were identified and a sub-cohort comprising 272 individuals was used for comparison. Among women in the 50-55 year age interval, homozygous carriers of the high-risk haplotype were at increased risk of lung cancer (RR=7.02, 95% CI=1.88-26.18). In the 56-60 year and 61-70 year age intervals, no associations were observed. Among men, no statistically significant associations were found in any age interval. Female homozygous carriers of the variant allele of XPD Lys751Gln were at significantly increased risk of lung cancer in the two younger age-intervals (50-55 years: RR=5.60, 95% CI=1.18-26.45, 56-60 years: RR=10.60, 95% CI=1.50-75.64). Among men, carriers of the variant allele of XPD Lys751Gln had a non-significantly increased risk of lung cancer in the youngest age interval (RR=6.38, 95% CI=0.74-54.90). When the polymorphisms in XPD Asp312Asn and Lys751Gln were mutually adjusted, XPD Asp312Asn was not associated with increased risk of cancer. We found no interaction between genotypes and duration of smoking. In conclusion, two regions of chromosome 19q13.2-3 seem to be associated with risk of lung cancer.

[Traffic-related air pollution at the place of residence and risk of cancer among children]. / Luftforurening fra trafik ved boligen og risiko for kraeft hos børn.

INTRODUCTION: The hypothesis that exposure to traffic-related air pollution increases the risk of cancer developing during childhood was investigated. MATERIALS AND METHODS: We enrolled 1,989 children notified to the Danish Cancer Registry with a diagnosis of leukaemia, tumour of the central nervous system (CNS), or malignant lymphoma during 1968-1991, and 5,506 control children selected at random from the entire childhood population. The residential histories of the children were traced from nine months before birth up to the time of diagnosis, as was a similar period for the controls. Information on traffic and the configuration of streets and buildings was collected for each of the 18,440 identified addresses. Concentrations of benzene and nitrogen dioxide (indicators of traffic-related air pollution) were calculated for the relevant residential periods, and combined into exposures to air pollution during pregnancy and childhood, respectively. RESULTS: The risks of leukaemia, CNS tumours, and all selected cancers combined were not related to exposure to benzene or nitrogen dioxide during either period. The risk of lymphomas increased by 25% (p for trend = 0.06) and 51% (p for trend = 0.05) for a doubling of the concentration of benzene and nitrogen dioxide, respectively, during the pregnancy. The association was restricted to Hodgkin's disease. DISCUSSION: On the basis of a low potential for selection bias, information bias, and confounding factors, we conclude that traffic-related air pollution at the residence of children is not linked to the risk of leukaemia or CNS tumour, which are the two major types of childhood cancer. The results indicated a possible association between air pollution and the risk of Hodgkin's disease, but the evidence allows of no firm conclusion at present.