Parental occupational exposure to chemicals and risk of breast cancer in female offspring.

OBJECTIVES: Parental exposure to chemicals at work has been hypothesized to be a potential predisposing factor for breast cancer in next generations. The objective of the present nationwide nested case-control study was to contribute with evidence to this area. METHODS: Women with primary breast cancer were identified using the Danish Cancer Registry and they were required to have information on either maternal or paternal employment history, which resulted in the inclusion of 5587 cases. For each case, 20 female cancer free controls were matched on year of birth using the Danish Civil Registration System. Employment history was linked to job exposure matrices to assess specific occupational chemical exposures. RESULTS: For maternal exposures, we observed an association between ever exposure to diesel exhaust (OR = 1.13, 95% CI: 1.01-1.27) and exposure to bitumen fumes in the perinatal period (OR = 1.51, 95% CI: 1.00-2.26) and breast cancer in female offspring. Highest cumulative exposure to benzo(a)pyrene, diesel exhaust, gasoline and bitumen fumes was further indicated to increase the risk. Results further indicated a stronger association between diesel exhaust (OR = 1.23, 95% CI: 1.01-1.50) and benzo(a)pyrene exposure (OR = 1.23, 95% CI: 0.96-1.57) and estrogen receptor negative tumors than tumors with ER expression, while bitumen fumes seemed to elevate the risk of both hormonal subtypes. For paternal exposures, the main results did not indicate any associations with breast cancer in female offspring. CONCLUSIONS: Our study suggests an elevated breast cancer risk in daughters of women occupational exposed to some occupational pollutants, including diesel exhaust, benzo(a)pyrene and bitumen fumes. These findings need to be confirmed in future large-scale studies before any firm conclusions can be reached.

Incident skin melanoma in Danish male military pilots: a nested case-control study.

OBJECTIVES: A growing body of research has reported that pilots have an increased risk of skin melanoma, which may be caused by occupational exposure to cosmic and solar ultraviolet A radiation in aircraft cockpits. However, the existing literature cannot rule out confounding, for example, that pilots may spend more leisure time in the sun compared with the general population, which therefore leaves the current evidence inconclusive. The present study aimed to provide more knowledge regarding this association. METHODS: This nested case-control study included 199 male cases of skin melanoma diagnosed between 1990 and 2003, and 1126 male cancer-free controls identified from a large Danish military population. Among these individuals, 10 cases had ever worked as a pilot.Detailed information on military service and other held jobs together with socioeconomic and lifestyle characteristics, for example, leisure-time sun exposure habits, had been obtained from a structured questionnaire. RESULTS: Adjusted results showed a positive association between work onboard aircraft and skin melanoma (OR=2.30, 95% CI: 1.06-4.97) and the risk was indicated only to be increased in pilots (OR=7.08, 95% CI: 2.51-19.93). A positive association between longer duration of employment as a pilot and skin melanoma was also observed (ORper year=1.07, 95% CI: 1.01-1.14). CONCLUSIONS: The findings from this study conducted among Danish military personnel suggest that pilots have an increased risk of skin melanoma after accounting for leisure-time sun exposure and socioeconomic status. Future large-scale studies focusing on the risk of skin melanoma in pilots, including detailed objective information on dimensions of exposure and potential confounders, are warranted.

Air pollution with NO2, PM2.5, and elemental carbon in relation to risk of breast cancer- a nationwide case-control study from Denmark.

Air pollution with particulate matter is an established lung carcinogen. Studies have suggested an association with breast cancer, but the evidence is inconsistent. METHODS: From nationwide registers, we identified all breast cancer cases (n = 55 745) in Denmark between 2000 and 2014. We matched one control for each case on age and year of birth. We used a multi-scale dispersion model to estimate outdoor concentrations of particulate matter <2.5 µm (PM2.5), elemental carbon (EC) and nitrogen dioxide (NO2) as time-weighted average over all addresses up to 20 years prior to diagnosis. We calculated odds ratios (OR) and 95% confidence intervals (CI) by conditional logistic regression with adjustment for marital status, educational level, occupational status, personal income, region of origin, medication and area-level socio-economic indicators. RESULTS: A 10 µg/m3 higher PM2.5 was associated with an OR for breast cancer of 1.21 (95% CI: 1.11-1.33). The corresponding ORs for EC (per 1 µg/m3) and NO2 (per 10 µg/m3) were 1.03 (95% CI: 1.00-1.07) and 1.03 (95% CI: 1.01-1.06), respectively. In multi-pollutant models, the OR for PM2.5 changed only little, whereas ORs for EC or NO2 approached the null. In an analysis of persons below 55 years, PM2.5 was associated with an OR of 1.32 (95% CI: 1.09-1.60) per 10 µg/m3 increase. CONCLUSION: We found evidence of an association between the investigated air pollutants and breast cancer, especially PM2.5. There were indications that the association differed by age at diagnosis. We were not able to include all potential confounders and thus, results should be interpreted with caution.

Colorectal cancer and occupational exposure to solar ultraviolet B radiation in Denmark.

OBJECTIVES: Solar ultraviolet B radiation (UV) may reduce the risk of cancer, including colorectal cancer (CRC), although the evidence is inconclusive. To contribute with evidence, the present largescale register-based nested case-control study aimed to investigate the association between occupational UV exposure and CRC in Denmark. METHODS: The Danish Cancer Registry was used to identify a total of 12,268 men and women diagnosed with primary CRC before age 70. Five controls matched on year of birth and sex, alive and free of CRC at the time of diagnosis of the index case were randomly selected from The Danish Civil Registration System. Occupational UV exposure was assessed by obtainment of full employment history from the Danish Supplementary Pension Fund Register, which was linked to a job exposure matrix. Conditional logistic regression was used to estimate odds ratios (ORs) with corresponding 95% confidence intervals. RESULTS: We observed an inverse association between longer duration of UV exposure and CRC in women (≥20 years: OR = 0.84, 95% CI: 0.69-1.03), while no noteworthy associations were observed in men. When focusing on colon cancer only, longer duration of UV exposure (>20 years: OR = 0.92, 95% CI: 0.83-1.01) and higher cumulative UV exposure (highest exposure category: OR = 0.90, 95% CI: 0.83-0.99) were indicated to lower the risk in the study population including both men and women, although the risk reduction appeared to be more evident for women. No consistent risk patterns were observed for rectal cancer. CONCLUSIONS: The present study suggests a modest protective effect from long-term occupational UV exposure on the risk of colon cancer. The effect may be greater in women and these findings need further attention in future large-scale studies.

Occupational exposure to solar ultraviolet B radiation and risk of prostate cancer in Danish men.

OBJECTIVES: Former epidemiological studies have indicated that solar ultraviolet B radiation (UV) may reduce the risk of prostate cancer, however, the evidence is inconclusive. To contribute with evidence, the present study aimed to evaluate the association between occupational UV exposure and prostate cancer in Danish men. METHODS: A total of 12,268 men diagnosed with primary prostate cancer before age 70 were identified via the Danish Cancer Registry. The Danish Civil Registration System was used to randomly select five male controls matched on year of birth, alive and free of prostate cancer at the time of diagnosis of the index case. Full individual-level employment history was retrieved from the Danish Supplementary Pension Fund Register and linked to a job exposure matrix to assess occupational UV exposure. Conditional logistic regression was used to estimate odds ratios (ORs) with corresponding 95 % confidence intervals. RESULTS: We observed an inverse association between ever exposure to occupational UV and prostate cancer (OR=0.93, 95 % CI: 0.89-0.97). Longer duration of exposure (≥20 years: OR=0.90, 95 % CI: 0.84-0.96) and highest cumulative exposure (OR=0.90, 95 % CI: 0.84-0.96) were both inversely associated with disease risk. CONCLUSIONS: The present study indicates a modest protective effect from occupational UV exposure on the risk of prostate cancer. This finding needs further attention in future large-scale studies.

Risk of breast cancer in Danish women occupationally exposed to organic solvents, including ethanol.

BACKGROUND: Organic solvents have been suggested to increase the risk of breast cancer although the epidemiologic evidence is limited. This study explored the association between organic solvents and breast cancer. METHODS: This nested population-based case-control study comprised 845 women with primary breast cancer initially identified in the Danish Cancer Registry between 2000 and 2003, and 1500 controls matched on year of birth who were randomly selected from the Danish Civil Registration System. Information on occupational exposure to organic solvents, and specifically ethanol, as well as risk factors for breast cancer was collected through structured interviews. RESULTS: For organic solvents, an increased risk was indicated for ever-exposure (odds ratio = 3.20, 95% confidence interval: 2.27-4.52), however, no noteworthy risk patterns were detected when exploring duration of exposure and cumulative exposure. Ever-exposure to organic solvents was associated with an increased risk of estrogen receptor negative and positive tumors as well as pre- and postmenopausal breast cancer. No associations were detected between occupational exposure to ethanol and breast cancer. CONCLUSIONS: This study indicates a positive association between organic solvents and breast cancer.

Occupational exposure to solar ultraviolet B radiation and risk of subtypes of breast cancer in Danish women.

OBJECTIVES: Previous epidemiological studies have indicated that solar ultraviolet B radiation (UVR) may have a protective effect on breast cancer. However, the evidence remains inconclusive. Despite the fact that outdoor work history may be considered a reliable measure of long-term UVR exposure, objective information on lifetime employment has not been included in previous investigations focusing on breast cancer. To address this issue, we explored the association between occupational UVR exposure and female breast cancer, including subtypes. METHODS: A total of 38 375 women under the age of 70 years were identified with primary breast cancer using the Danish Cancer Registry. Five female controls born on the same year, alive and free of breast cancer at the time of diagnosis of the index case, were randomly selected from the Danish Civil Registration System. The Danish Supplementary Pension Fund Register was used to retrieve full employment history, and a job exposure matrix was used to assess occupational UVR exposure. Conditional logistic regression with adjustment for important confounders was used to estimate the OR. RESULTS: We observed no overall association between occupational UVR exposure and breast cancer. After the age of 50 years, longer duration of UVR exposure (≥20 years: OR=0.83, 95% CI 0.75 to 0.92) and highest cumulative exposure (OR=0.89, 95% CI 0.83 to 0.95) were inversely associated with risk. Our results did not reflect any notable risk difference by oestrogen receptor status. CONCLUSIONS: This study indicates an inverse association between long-term occupational UVR exposure and late-onset breast cancer. This finding needs further attention in future occupational studies.

Breast cancer among Danish women occupationally exposed to diesel exhaust and polycyclic aromatic hydrocarbons, 1964-2016.

Objective The aim of this study was to explore the association between occupational exposure to diesel exhaust and polycyclic aromatic hydrocarbons (PAH), respectively, and breast cancer subtypes. Methods The study included 38 375 women <70 years with incident breast cancer, identified in the Danish Cancer Registry, and 5 breast cancer-free controls per case who were randomly selected from the Danish Civil Registration System and matched on year of birth. Full employment history was obtained for all study subjects from a nationwide pension fund, and exposure to diesel exhaust and PAH was assessed using a job exposure matrix. Conditional logistic regression was used for estimation of odds ratios (OR) with adjustment for reproductive factors and socioeconomic status. Results No noteworthy associations were observed for overall breast cancer in women exposed to diesel exhaust. However, diesel exhaust modestly elevated the risk of estrogen receptor negative breast tumors before age 50 [OR 1.26, 95% confidence interval (CI) 1.09-1.46]. Duration- and dose-response relationships were further observed for this subtype in this age group. No notable risk patterns were generally observed for PAH exposure. Conclusion Occupational exposure to diesel exhaust may increase the risk of early-onset estrogen receptor negative breast tumors in women. Future studies exploring this association are warranted.

Occupational exposure to specific organic solvents and risk of subtypes of breast cancer in a large population of Danish women, 1964-2016.

OBJECTIVE: To explore associations between occupational exposure to four specific organic solvents, respectively, and female breast cancer, including subtypes. METHODS: Using the Danish Cancer Registry, we identified 38 375 women under age 70 years with primary breast cancer. Five randomly selected breast-cancer-free controls per case matched on year of birth were retrieved from the Danish Civil Registration System . A nationwide pension fund was used to retrieve full employment history, and exposure to 1,1,1-trichloroethane, trichloroethylene (TCE), benzene and toluene was assessed using a job exposure matrix. ORs were estimated using conditional logistic regression with adjustment for reproductive factors and socioeconomic status. RESULTS: Overall results indicated no noteworthy associations between the specific organic solvents and breast cancer before and after age 50 years, except for a small increased risk after age 50 in women exposed to TCE (OR=1.15, 95% CI: 0.97-1.36). After age 50 years, exposure to TCE was associated with a small increased risk in women with over 20 years of latency (OR=1.26, 95% CI: 1.02-1.56). Further, an increased risk of oestrogen receptor positive (ER+) tumours was also observed (OR=1.21, 95% CI: 1.01-1.47), and high cumulative exposure and longer latency also increased the risk of this subtype. CONCLUSION: This study provides limited evidence supporting the association between occupational exposure to each of the four organic solvents and breast cancer. The risk of ER+ breast tumours after age 50 years may be increased in women with TCE exposure, and this possible association therefore needs further attention in future studies.

Historical changes in chemical exposures encountered by Danish firefighters.

Objective This study aimed to demonstrate the possibility of using history science methods in occupational studies by evaluating overall historical changes in Danish firefighting modifying chemical exposures from smoke and fire trucks. Methods Data on changes in Danish firefighting after World War II were searched for in both museums and the Danish library catalogue REX, accessing collections of literature from all institutes of the University of Copenhagen and the Danish Royal Library. Results Several historical changes were identified either increasing or reducing chemical exposures in Danish firefighting. New sources of chemical exposures included more toxic smoke combustion from plastic materials introduced in the 1950s, exhaust from new diesel engines introduced in the 1960s and new assignments relating to chemical cleanups in the 1970s and traffic accidents in the 1990s. Nevertheless, several improvements in the profession`s work environment may have reduced chemical exposures, for example, mandatory use of more effective respiratory protection equipment in the 1970s, incorporation of mechanical exhaust systems in the 2000s, and filters and selective catalytic reduction (SCR) for diesel engines in the 2010s. Conclusion The data showed that the work environment in Danish firefighting has undergone several improvements during the last decades. At the same time, however, several new chemical hazards have also been introduced. Consequently, no strong conclusions as to whether Danish firefighting overall has become a less hazardous profession can be made.

Risk of asthma and chronic obstructive pulmonary disease in a large historical cohort of Danish firefighters.

OBJECTIVE: Firefighters are exposed to numerous respiratory hazards, but large studies on the risk of pulmonary disease are scarce. The objective of this study was to examine incidence of asthma and chronic obstructive pulmonary disease (COPD) in a nationwide cohort of Danish firefighters. METHODS: We used individual historical employment records on 11 968 Danish male firefighters primarily supplied by trade unions and fire agencies. Furthermore, we used the Supplementary Pension Fund Register to form an occupational reference group consisting of military employees. Information on respiratory incidence was retrieved from the nationwide Danish National Patient Registry. Age and calendar time standardised incidence ratio (SIR) and Poisson regression analyses (incidence rate ratio) were used for estimation of risks, including 95% CIs. RESULTS: Compared with military employees, the overall age and calendar-time adjusted risk for asthma was significantly increased among full-time firefighters (SIR=1.58, 95% CI 1.32 to 1.88), but not among part-time/volunteer firefighters. Full-time firefighters' risk for asthma did not vary by duration of employment. No consistent evidence of an increased risk for chronic obstructive pulmonary disease was detected. CONCLUSION: Danish firefighters have an increased risk of asthma, but the causes, whether occupational or not, remain to be established.

Assessment of polycyclic aromatic hydrocarbon exposure, lung function, systemic inflammation, and genotoxicity in peripheral blood mononuclear cells from firefighters before and after a work shift.

Firefighting is regarded as possibly carcinogenic, although there are few mechanistic studies on genotoxicity in humans. We investigated exposure to polycyclic aromatic hydrocarbons (PAH), lung function, systemic inflammation and genotoxicity in peripheral blood mononuclear cells (PBMC) of 22 professional firefighters before and after a 24-h work shift. Exposure was assessed by measurements of particulate matter (PM), PAH levels on skin, urinary 1-hydroxypyrene (1-OHP) and self-reported participation in fire extinguishing activities. PM measurements indicated that use of personal protective equipment (PPE) effectively prevented inhalation exposure, but exposure to PM occurred when the environment was perceived as safe and the self-contained breathing apparatuses were removed. The level of PAH on skin and urinary 1-OHP concentration were similar before and after the work shift, irrespective of self-reported participation in fire extinction activities. Post-shift, the subjects had reduced levels of oxidatively damaged DNA in PBMC, and increased plasma concentration of vascular cell adhesion molecule 1 (VCAM-1). The subjects reporting participation in fire extinction activities during the work shift had a slightly decreased lung function, increased plasma concentration of VCAM-1, and reduced levels of oxidatively damaged DNA in PBMC. Our results suggest that the firefighters were not exposed to PM while using PPE, but exposure occurred when PPE was not used. The work shift was not associated with increased levels of genotoxicity. Increased levels of VCAM-1 in plasma were observed. Environ. Mol. Mutagen. 59:539-548, 2018. © 2018 Wiley Periodicals, Inc.

Mortality in a cohort of Danish firefighters; 1970-2014.

PURPOSE: Occupational exposure of firefighters involves a complex range of potential health threats from toxic chemicals, shift work, extreme heat, physical and emotional strain. The aim of this study is to examine overall and disease-specific mortality among Danish firefighters. METHODS: Through systematic collection of personnel and membership records from employers and trade unions, past and present male Danish firefighters were identified (n = 11,775). Using the unique Danish personal identification number, information on additional employment, vital status and cause of death was linked to each member of the cohort from the Supplementary Pension Fund Register, the Danish Civil Registration System and the Danish Register of Causes of Death. Standardized mortality ratios (SMRs) were calculated for specific causes of death using rates for two reference groups, a random sample of the male working population (n = 262,168) and the military (n = 396,739), respectively. RESULTS: Overall mortality was significantly reduced among the firefighters compared to both the sample of the working population and the military (SMR 0.74, 95% CI 0.69-0.78 and SMR 0.88, 95% CI 0.83-0.93). Further, the SMRs for endocrine diseases, mental disorders, non-traffic related accidents and other external causes were significantly lower against both reference groups. Death from stomach cancer was significantly increased among the full time firefighters, while part time/volunteer workers shared a significant increase in prostate cancer death compared to both references. CONCLUSIONS: Despite potential exposure to several occupational hazards, male Danish firefighters have a lower mortality than both the Danish working population in general and Danish military employees.

Incidence of cardiovascular disease in a historical cohort of Danish firefighters.

OBJECTIVES: Firefighters are exposed to multiple cardiovascular hazards, but few epidemiological studies have addressed their cardiovascular morbidity. The objective of this study was therefore to examine the incidence of cardiovascular diseases (CVD) in Danish firefighters. METHODS: We used individual historical employment records on 11.691 male Danish firefighters supplied by trade unions and fire agencies. The Supplementary Pension Fund Register was used to establish two occupational reference groups (a random sample from the male employed population and military employees). Information on CVD incidence was retrieved from the nationwide Danish National Patient Registry. SIRs and Poisson regression analyses (incidence rate ratio) were used for estimation of risks, including 95% CIs. RESULTS: In comparison with the population sample, the age-adjusted and calendar time-adjusted SIR for all CVDs combined was increased in firefighters (SIR=1.10, 95% CI 1.05 to 1.15). The risk was also elevated for the most frequent outcomes, including angina pectoris (SIR=1.16, 95% CI 1.08 to 1.24), acute myocardial infarction (SIR=1.16, 95% CI 1.06 to 1.26), chronic ischaemic heart disease (SIR=1.15, 95% CI 1.06 to 1.24) and atrial fibrillation/flutter (SIR=1.25, 95% CI 1.14 to 1.36). This analysis showed the most elevated SIRs for CVD in full-time firefighters compared with part-time/volunteer firefighters. Both types of firefighters employed <15 years had an increased risk of CVD. Similar risk patterns appeared in comparisons with the military. Internal analysis supported external findings. CONCLUSION: The risk of overall CVD, including the most frequent subtypes was modestly increased in Danish firefighters and was most elevated in full-time firefighters compared with other male employees.

Association between polycyclic aromatic hydrocarbon exposure and peripheral blood mononuclear cell DNA damage in human volunteers during fire extinction exercises.

This study investigated a number of biomarkers, associated with systemic inflammation as well as genotoxicity, in 53 young and healthy subjects participating in a course to become firefighters, while wearing personal protective equipment (PPE). The exposure period consisted of a 3-day training course where the subjects participated in various live-fire training exercises. The subjects were instructed to extinguish fires of either wood or wood with electrical cords and mattresses. The personal exposure was measured as dermal polycyclic aromatic hydrocarbon (PAH) concentrations and urinary excretion of 1-hydroxypyrene (1-OHP). The subjects were primarily exposed to particulate matter (PM) in by-stander positions, since the self-contained breathing apparatus effectively prevented pulmonary exposure. There was increased dermal exposure to pyrene (68.1%, 95% CI: 52.5%, 83.8%) and sum of 16 polycyclic aromatic hydrocarbons (Æ©PAH; 79.5%, 95% CI: 52.5%, 106.6%), and increased urinary excretion of 1-OHP (70.4%, 95% CI: 52.5%; 106.6%) after the firefighting exercise compared with the mean of two control measurements performed 2 weeks before and 2 weeks after the firefighting course, respectively. The level of Fpg-sensitive sites in peripheral blood mononuclear cells (PBMCs) was increased by 8.0% (95% CI: 0.02%, 15.9%) compared with control measurements. The level of DNA strand breaks was positively associated with dermal exposure to pyrene and Æ©PAHs, and urinary excretion of 1-OHP. Fpg-sensitive sites were only associated positively with PAHs. Biomarkers of inflammation and lung function showed no consistent response. In summary, the study demonstrated that PAH exposure during firefighting activity was associated with genotoxicity in PBMCs.

Long-term follow-up for cancer incidence in a cohort of Danish firefighters.

OBJECTIVES: To examine cancer incidence among Danish firefighters using several employment-related exposure subgroups. METHODS: A historical cohort of 9061 male Danish firefighters was established from collected personnel and membership records from employers and trade unions. Using the unique Danish personal identification number, information on additional previous employment, cancer and vital status was linked to members of the cohort from the Supplementary Pension Fund Register, the Danish Cancer Registry and the Danish Civil Registration System. SIRs were calculated for specific cancer types using rates for the general population, a sample of the working population and military employees, respectively. RESULTS: Compared with the selected reference groups, the overall observed incidence of cancer among the firefighters was at level with the expected (SIR 1.02, 95% CI 0.96 to 1.09 vs the general population). The SIR for colon cancer was consistently significantly reduced, while the slight excess seen for melanoma of the skin, prostate and testicular cancer compared with the general population was not reproduced using the military as reference. CONCLUSIONS: Previous associations with melanoma of the skin, prostate and testicular cancer are supported by our main results. However, the increase in incidence of these cancers is not reproduced using the military as reference. Similarities in cancer profile for the firefighters and the military point to shared risk factors in either lifestyle or work environment.

Cardiovascular health effects following exposure of human volunteers during fire extinction exercises.

BACKGROUND: Firefighters have increased risk of cardiovascular disease and of sudden death from coronary heart disease on duty while suppressing fires. This study investigated the effect of firefighting activities, using appropriate personal protective equipment (PPE), on biomarkers of cardiovascular effects in young conscripts training to become firefighters. METHODS: Healthy conscripts (n = 43) who participated in a rescue educational course for firefighting were enrolled in the study. The exposure period consisted of a three-day training course where the conscripts participated in various firefighting exercises in a constructed firehouse and flashover container. The subjects were instructed to extinguish fires of either wood or wood with electrical cords and mattresses. The exposure to particulate matter (PM) was assessed at various locations and personal exposure was assessed by portable PM samplers and urinary excretion of 1-hydroxypyrene. Cardiovascular measurements included microvascular function and heart rate variability (HRV). RESULTS: The subjects were primarily exposed to PM in bystander positions, whereas self-contained breathing apparatus effectively abolished pulmonary exposure. Firefighting training was associated with elevated urinary excretion of 1-hydroxypyrene (105%, 95% CI: 52; 157%), increased body temperature, decreased microvascular function (-18%, 95% CI: -26; -9%) and altered HRV. There was no difference in cardiovascular measurements for the two types of fires. CONCLUSION: Observations from this fire extinction training show that PM exposure mainly occurs in situations where firefighters removed the self-contained breathing apparatus. Altered cardiovascular disease endpoints after the firefighting exercise period were most likely due to complex effects from PM exposure, physical exhaustion and increased core body temperature.