Jorunn Kirkeleit

Increased risk of acute myelogenous leukemia and multiple myeloma in a historical cohort of upstream petroleum workers exposed to crude oil.

Benzene exposure has been shown to be related to acute myelogenous leukemia, while the association with multiple myeloma and non-Hodgkin lymphoma has been a much-debated issue. We performed a historical cohort study to investigate whether workers employed in Norway’s upstream petroleum industry exposed to crude oil and other products containing benzene have an increased risk of developing various subtypes of hematologic neoplasms. Using the Norwegian Registry of Employers and Employees we included all 27,919 offshore workers registered from 1981 to 2003 and 366,114 referents from the general working population matched by gender, age, and community of residence. The cohort was linked to the Cancer Registry of Norway. Workers in the job category “upstream operator offshore”, having the most extensive contact with crude oil, had an excess risk of hematologic neoplasms (blood and bone marrow) (rate ratio (RR) 1.90, 95% confidence interval (95% CI): 1.19–3.02). This was ascribed to an increased risk of acute myelogenous leukemia (RR 2.89, 95% CI: 1.25−6.67) and multiple myeloma (RR 2.49, 95% CI: 1.21–5.13). There were no statistical differences between the groups in respect to non-Hodgkin lymphoma. The results suggest that benzene exposure, which most probably caused the increased risk of acute myelogenous leukemia, also resulted in an increased risk of multiple myeloma.

Risk of MS is not associated with exposure to crude oil, but increases with low level of education

Background: Offshore workers in the Norwegian upstream petroleum industry are exposed to a number of chemicals such as organic solvents, mineral oils and other hydrocarbons, possibly contributing to an increased risk of multiple sclerosis (MS). Objective: To estimate the risk of MS in this population compared with the general working population in Norway, adjusting for education. Methods: Using the Norwegian Registry of Employers and Employees we included all 27,900 offshore workers registered from 1981 to 2003 and 366,805 referents from the general working population matched by gender, age and community of residence. The cohort was linked to the Norwegian MS Registry and the Norwegian Education Registry. Results: There was no increased risk of MS among the offshore workers. We found a marked and linear inverse relationship between level of education and the risk of MS in the total study population, with a rate ratio of 0.48 (95% CI, 0.53 to 0.88) for workers with a graduate degree compared to workers with elementary school only. Conclusions: These findings do not support a major aetiological role of petroleum-based products, but rather point to smoking and other lifestyle factors related to the level of education as being important for the risk of MS.

Increased risk of oesophageal adenocarcinoma among upstream petroleum workers.

Objectives To investigate cancer risk, particularly oesophageal cancer, among male upstream petroleum workers offshore potentially exposed to various carcinogenic agents. Methods Using the Norwegian Registry of Employers and Employees, 24 765 male offshore workers registered from 1981 to 2003 was compared with 283 002 male referents from the general working population matched by age and community of residence. The historical cohort was linked to the Cancer Registry of Norway and the Norwegian Cause of Death Registry. Results Male offshore workers had excess risk of oesophageal cancer (RR 2.6, 95% CI 1.4 to 4.8) compared with the reference population. Only the adenocarcinoma type had a significantly increased risk (RR 2.7, 95% CI 1.0 to 7.0), mainly because of an increased risk among upstream operators (RR 4.3, 95% CI 1.3 to 14.5). Upstream operators did not have significant excess of respiratory system or colon cancer or mortality from any other lifestyle-related diseases investigated. Conclusion We found a fourfold excess risk of oesophageal adenocarcinoma among male workers assumed to have had the most extensive contact with crude oil. Due to the small number of cases, and a lack of detailed data on occupational exposure and lifestyle factors associated with oesophageal adenocarcinoma, the results must be interpreted with caution. Nevertheless, given the low risk of lifestyle-related cancers and causes of death in this working group, the results add to the observations in other low-powered studies on oesophageal cancer, further suggesting that factors related to the petroleum stream or carcinogenic agents used in the production process might be associated with risk of oesophageal adenocarcinoma.

Acute suppression of serum IgM and IgA in tank workers exposed to benzene

We investigated associations between benzene exposure and alterations of proteins and cells of the immune system among workers maintaining cargo tanks containing crude oil residues. Individual exposure to benzene, benzene in blood and urine, peripheral blood lymphocytes (total lymphocytes, lymphocytes in subpopulations CD3, CD4, CD8, CD19, CD56 and CD4/CD8 ratio), complement factors C3 and C4 and serum concentration of immunoglobulins (IgG, IgA, IgM and IgE) were analysed among 13 tank workers and nine unexposed referents (catering section). Benzene exposure was measured during three consecutive 12‐h work days. Blood and urine samples were collected pre‐shift on the first day (baseline), post‐shift on the third day, and pre–next shift on the following morning. The time spent in the cargo tank was logged. The individual geometric mean benzene exposure in the breathing zone of tank workers over 3 days was 0.15 p.p.m. (range 0.01–0.62 p.p.m.) (n = 26). The geometric mean benzene concentration in blood post‐shift was 12.3 nmol/l among tank workers versus 0.7 nmol/l among the referents. Tank workers showed a decline (versus referents) in IgM from baseline to post‐shift (t‐test, P = 0.04) and IgA from baseline to pre–next shift (t‐test, P = 0.01). They also showed a decline in CD4 T cells from baseline to post‐shift (t‐test, P = 0.04). Suppression correlated with benzene exposure, benzene concentrations in blood and urine and time spent in the tank. The groups did not differ significantly in the change in other immune parameters. The clinical significance is unknown and warrants further studies.

Effects of Benzene on human hematopoiesis

Benzene, an aromatic hydrocarbon that is a natural component of crude oil and natural gas, is toxic to the blood and blood-forming organs. Epidemiological studies have established an association between benzene exposure and acute myeloid leukemia, and increasing evidence also indicates a possible association between benzene and multiple myeloma. A specific benzene-associated myelodysplastic syndrome has also been suggested. Chronic hematotoxic effects of ben- zene exposure, including reduced lymphocyte, neutrophil and platelet counts in peripheral blood, have been detected at occupational exposure below a level that had previously been considered not to cause any health effects. Whether these abnormalities represent bone marrow damage and/or initial events in the development of a true neoplastic disease is not known. Together with a reported nonlinear relationship between benzene exposure and the level of various metabolites, favoring production of biologically reactive quinones at exposure below 1 part per million, these observations suggest that benzene even at low exposure levels may contribute to the risk of acute myeloid leukemia or myelodysplastic syndrome, especially among genetically susceptible individuals.

Ultraviolet radiation and skin cancer risk in offshore workers

Background Excess skin cancer mortality and incidence have been reported among both land-based and offshore petroleum workers. The association between skin cancer and ultraviolet radiation (UVR) exposure has not been examined in these workers, although they have long off-duty periods and high average income that may allow travelling to sunny destinations. In addition, they have access to solariums free of charge on many accommodation platforms. Aims To prospectively examine risk of incident cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC), according to sun-tanning habits with adjustment for aromatic hydrocarbon exposure. Methods A cohort of men employed offshore from 1965 to 1999 was linked through the Cancer Registry of Norway 1999-2012. Cox regression adapted to a stratified case-cohort design was used to estimate hazard ratios with 95% confidence intervals. Results The cohort included 24917 men. During 13.5 years of follow-up, 112 CMs and 70 NMSCs occurred. A positive dose-response relationship was seen between sunburn frequency and risk of CM (Ptrend < 0.05) and NMSC (Ptrend < 0.01). Solarium use both before and after age 20 was related to increased risk of NMSC. Sunscreen use was associated with increased risk of NMSC (Ptrend < 0.001). Conclusions UVR exposure seems to be a significant contributor to the elevated risk of skin cancer observed in North Sea offshore workers. The positive association between solarium use and NMSC risk adds to the growing body of literature on artificial UV devices as carcinogenic.

Global Gene Expression Response in Peripheral Blood Cells of Petroleum Workers Exposed to Sub-Ppm Benzene Levels

Altered gene expression in pathways relevant to leukaemogenesis, as well as reduced levels of circulating lymphocytes, have been reported in workers that were exposed to benzene concentrations below 1 ppm. In this study, we analysed whole blood global gene expression patterns in a worker cohort with altered levels of T cells and immunoglobulins IgM and IgA at three time points; pre-shift, post-shift (after three days), and post-recovery (12 hours later). Eight benzene exposed tank workers performing maintenance work in crude oil cargo tanks with a mean benzene exposure of 0.3 ppm (range 0.1–0.5 ppm) and five referents considered to be unexposed were examined by gene expression arrays. By using our data as independent validation, we reanalysed selected genes that were reported to be altered from previous studies of workers being exposed to sub-ppm benzene levels Four out of six genes previously proposed as marker genes in chronically exposed workers separated benzene exposed workers from unexposed referents (CLEC5, ACSL1, PRG2, IFNB1). Even better separation of benzene exposed workers and referents was observed for short-term exposure for genes in the Jak-STAT pathway, particularly elevated expression of IL6 and reduced expression of IL19.

Hypersensitivity pneumonitis in fish processing workers diagnosed by inhalation challenge

Workers in the fish processing industry have increased risk of developing respiratory diseases due to occupational exposure to bioaerosols and related allergens [1–4]. The literature reports more occupational asthma in workers handling salmon [2, 5], and an exposure–response relationship between total protein exposure and cross-shift changes in forced expiratory volume in 1 s (FEV1) and lower respiratory tract symptoms [6]. To our knowledge, there are no published reports on hypersensitivity pneumonitis from this industry. Hypersensitivity pneumonitis is a complex disease for which there are no generally accepted diagnostic criteria, particularly at earlier stages of the disease. We present the case of a fish processing worker diagnosed with hypersensitivity pneumonitis caused by proteins from salmon, in which the aetiology was established using specific inhalation challenge (SIC) as a diagnostic tool. Hypersensitivity pneumonitis may be caused by occupational exposure in the fish processing industry http://ow.ly/GbEf30lFnyk

0358 Rhinitis symptoms and immunological response after occupational exposure to shrimp shell powder

Occupational bioaerosol exposure may cause a range of temporary or permanent health effects , depending on host factors and the type and duration of exposure. In the present study, we investigated rhinitis and immunological markers in all employees in a shrimp shell powder production factory, before and after exposure to shrimp shell powder. Material and methods The study population comprised 11 employees. Personal exposure to inhalable dust (fullshift) was measured in the breathing zone of the employees during production of shrimp shell powder. All employees answered a self-administered questionnaire before and after exposure, about working tasks, airways symptoms, and smoking habits. Blood samples were collected before and after the work shift, and analysed for leukocyte counts, tryptase, total IgE, IgA, IgM, IgG. Results Shirmp shell powder workers were exposed to 12 mg/m3 inhalable dust (mean 11,8 mg/m3, median 8.2 mg/m3, n=16), the exposure level for unexposed group was less than 1 mg/m3 inhalable dust (mean 0.4 mg/m3, median 0.4 mg/m3 , n=10). Employees working with shrimp shell powder had more rhinitis symptoms (stuffy nose and runny nose) than employees working with fish. Although not statistically significant, the peripheral levels of tryptase, leucocytes and neutrophils in peripheral blood appeared to be highest among exposed workers, increasing after exposure. Conclusions Shrimp shell powder workers are exposed to high level of inhalable dust compared to the occupational exposure limit of organic dust (5 mg/m3). Exposure was related to more rhinitis symptoms and indicated (non-significantly) higher immunological parameters Follow-up of this industry and more study is needed.

0066 Maternal occupational exposure to benzene increases the risk of childhood leukaemia in offspring – a prospective study in the norwegian mother and child cohort study

Introduction There is an established causal relationship between benzene exposure and acute myelogenous leukaemia in adults, but the association between parental benzene exposure and childhood leukaemia in offspring remains inconclusive. Objective Using the prospective population-based Norwegian Mother and Child Cohort Study (MoBa) comprising 1 13 754 offspring (1999–2009), we investigated the association between parental exposure to ”gasoline or exhaust” as a proxy to benzene exposure and childhood leukaemia. Method Around the 17th gestational week mothers and fathers responded to questions on a range of occupational exposures during the last 6 months and pre-conception, respectively. Exposure to benzene was assessed through self-reported exposure to ”gasoline or exhaust” (”never exposed”, ”ever exposed” and ”exposed>30 days”), the latter interpreted as being occupational. Development of subsequent childhood leukaemia (n=70) were identified through linkage with the Cancer Registry of Norway. The risk was estimated by odds ratios (OR) with 95% confidence intervals (95% CI) comparing the offspring from exposed and unexposed parents using a logistic regression model, adjusting for maternal smoking and birth weight. Results Maternal exposure was associated with an increased risk of childhood leukaemia (OR 2.6; 95% CI 1.03, 6.50). The risk increased with number of days being exposed during the last 6 months categorised in ”0”, ”1–30”, ”31–180” (p-value for trend=0.03). No excess risk of leukaemia was found for paternal exposure. Conclusion We found an excess risk of leukaemia in children having a mother reporting being exposed to benzene-containing ”gasoline or exhaust” prior to and/or during pregnancy.