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Lymphohematopoietic Malignancies and Oil Exploitation in KoprivnicaKrizevci County, Croatia DAVORKA GAZDEK, MD, MSC, MARIJA STRNAD, MD, PHD, JADRANKA MUSTAJBEGOVIC, MD, PHD, ZLATKA NEMET-LOJAN, MD To determine lymphohematopoietic malignancy incidence rates between populations living near oilgas fields (two regions) compared with those living in areas free from oil-gas exploitation (one region) in KoprivnicaKrizevci County, Croatia, 803 new cases of lymphohematopoietic malignancies were studied for two time periods: 19711980 (prior to oilgas exploitation) and 19812000 (during oilgas exploitation). The results showed considerable geographic differences in the incidences of chronic myeloid leukemia and multiple myeloma. The authors conclude that proximity to oil or gas fields represents an increased population risk of developing lymphohematopoietic cancers. Key words: crude oil; natural gas; hematopoietic malignancies; leukemia; lymphoma; Croatia. INT J OCCUP ENVIRON HEALTH 2007;13:258267 T he oldest and largest crude oil and natural gas field in Croatia is in KoprivnicaKrizevci County (Figure 1). Although gas and oil deposits were discovered in 1960s, major exploitation (drilling, extracting, and hydrocarbon production) started in February 1981.1,2 There are 90 production wells in the county, half of which are in the Djurdjevac region, and the other half in the Koprivnica region (Figure 2; Table 1). The Djurdjevac region alone produces around 50% of Croatian gas, which is about 30% of primary source of Croatian energy.13 The oilgas fields in KoprivnicaKrizevci County are situated at depths between 3,500 and 4,000 m, under extremely high pressure (500 bars), at temperatures of 180200C, and contain high concentrations of carbon dioxide (1024%), as well as hydrogen sulfide (0.0070.01%) and mercury (1001500 g/m3).2,3 As Figure 3 shows, production fluid is brought in from all wells to the Central Gas Treatment Plant in the Djurdjevac region for separation of the liquid phase (oil and formation water) from the gaseous phase, gas dehydration, and removal of carbon dioxide, hydrogen sulfide, and mercury. Hydrogen sulfide, partially transformed into elementary sulfur in form of sulfide mud, is partially released into atmosphere with carbon dioxide. From the Central Gas Treatment Plant to refineries, crude oil is transported by the Adriatic Oil Pipeline (JANAF).13 Drilling and extraction of crude oil and natural gas, separation, and dehydration take place in an enclosed system with only a small possibility for human exposure. However, the production process also creates harmful components such as mercury, carbon dioxide, sulfide compounds (hydrogen sulfide and mercapteneRSH) and formation water.2,3 In order to control and improve the efficiency of an industrial facility, a comprehensive environmental monitoring program was established (1990, 1995/1996, and annually beginning in 1999).4 Monitoring included measurements of the main pollutants in ambient air (mercury, carbon dioxide, hydrogen sulfide, mercapteneRSH), as well as metals such as cadmium, molybdenum, cobalt, lead, Received from the Institute of Public Health, KoprivnicaKrizevci County, Koprivnica, Croatia (DG); the Croatian National Institute of Public Health, Zagreb, Croatia (MS); the School of Public Health "Andrija Stampar," Medical Faculty University of Zagreb, Zagreb, Croatia (JM); and General Hospital "Dr. Tomislav Bardek," Koprivnica, Croatia (ZN-L). Address correspondence and reprint requests to: Davorka Gazdek, MD, Institute of Public Health, KoprivnicaKrizevci County, Florijanski trg 4, 48 000 Koprivnica, Croatia; telephone: +385 48 221 875; fax: + 385 48 622 994; e-mail: <szjz@kc.htnet.hr>. Figure 1--Map of Croatia with KoprivnicaKrizevci County marked. 258 zinc, copper, vanadium, chrome, and barium in soil. In order to determine the level of mercury present, the National Petroleum Company constructed appropriate process units at the Central Gas Treatment Plant, which became operative in February 1992.2,3 Mercury removal has been accomplished by the use of sulfurimpregnated activated carbon. The efficiency of mercury adsorption from gas has been found to be 8999%.5 The desulfurization unit (conversion of hydrogen sulfide into elemental sulfur) at the Central Gas Treatment Plant was put into operation in the early 1990s. Until the concentration of hydrogen sulfide released at the plant outlet into the atmosphere was reduced, the mercapteneRSH concentration remained high. Dehydration is accomplished by glycol, which absorbs benzene and other organic components.6 This process also emits organic compounds.7 Drilling wastes (drilling mud and formation water) are deposited into pits until wastewater spills directly into nearby streams. Geochemical and mineralogical assessments of materials from two already closed pits showed higher than normal concentrations of mercury, lead, total hydrocarbons, BTEX, and polycyclic aromatic hydrocarbons in spite of lime stabilizzation of the waste.9 These byproducts of oilgas exploitation represent potential problems that affect the environment and the health of local populations. Inhabitants of rural areas of KoprivnicaKrizevci County drink only well water because only towns and their surrounding areas have piped-in drinking water.8 A special facility for treatment of liquid waste from oilgas production is being built and will be finished in 2007.6 There have been few studies done on the effects of exposures to oil and gas on human health. The IARC/WHO found that carcinogenic effects of exposures to crude oil and natural gas are few, but that pos- Figure 2--Map of KoprivnicaKrizevci County with Djurdjevac, Koprivnica, and Krizevci regions marked, as well as oil fields (vertical lines), gas fields (horizontal lines), and Central Gas Treatment Plant (CGP). sible hematologic carcinogens in oil and gas, benzene being the most familiar, but also 1,3-butadiene and polycyclic aromatic hydrocarbons, might be related to environmentally induced cancers.10 Most of the available research has been done on workers who have had contact with benzene during production, processing, or transport.1116 Those studies show that exposure to benzene increases the risk for developing myeloid leukemia, especially acute myeloid leukemia, while relationships with other subtypes of lymphohematopoietic malignancies are questionable. Only a few studies mention the effect of proximity to oil fields on the emergence of cancer in general populations. Most of these studies show that living near oil fields increases the risk for developing lymphohematopoietic malignancies, and particularly myeloid leukemia.11,1719 TABLE 1 OilGas Fields in KoprivnicaKrizevci County, Croatia Year Beginning Exploitation Number of Wells (12/31/01) Djurdjevac Field 1 Field 2 Field 3 Field 4 Total 1981 1985 1987 1970 19 gas 13 gas 4 gas 7 (3 gas + 4 oil) 43 Koprivnica Field 5 Field 6 Field 7 Field 7 Field 8 Field 9 Total *Oilgas fields (see Figure 2). 1966 1971 1987 2000 1988 1985 19 (18 oil+1 gas) 6 oil 3 gas 2 gas 1 gas 6 gas 37 ________________P_r_o_d_u__c_t_io_n__i_n_2__0_0_1________________ Oil (t) Gas (1,000m3) Condensate (t) 3,387 3,387 987,402 375,847 827 4,480 1,368,556 48,475 127,600 176,075 10,691 870 11,561 3,216 15,657 154,565 954 19,091 193,483 150 21,876 666 22,692 VOL 13/NO 3, JUL/SEP 2007 www.ijoeh.com Lymphohematopoietic Malignancies 259 Figure 3--Oil-gas recovery from wells, Koprivnica-Krizevci County. The effect of natural gas and crude oil exploitation on the population's health in KoprivnicaKrizevci County had not previously been studied, the exception being the study of mercury levels in urine of workers in oil and gas facilities, inhabitants of a village in the Djurdjevac region and a village in the Krizevci region. The results of that research indicated that the mercury levels were within normal limits, but also that the inhabitants of the village in the Krizevci region had lower levels of mercury than did those in the Djurdjevac region.20 The objective of this study was to determine whether there were any differences in incidence rates of lymphohematopoietic malignancies, all cases of leukemia, Hodgkin's and non-Hodgkin's lymphomas, multiple myeloma, acute and chronic lymphoid leukemia, and acute and chronic myeloid leukemia between populations living in the proximity of oilgas fields and those living in region free from oilgas exploitation in KoprivnicaKrizevci County. METHODS Study Area KoprivnicaKrizevci County is situated in the north of Croatia, on the border with Hungary (Figure 1). According to the 2001 Census, there are 124,467 inhabitants in the County. It consists of three regions: Djurdjevac, Koprivnica and Krizevci. The Djurdjevac region covers an area of 509.41 km2 and has 27,063 inhabitants, the Koprivnica region covers an area of 742.90 km2, with 60,669 inhabitants, and the Krizevci region covers an area of 494.09 km2 and has 36,735 inhabitants. There are three main towns, with 50% of the County population.8 Piped-in drinking water is supplied to the town areas, while the rural population has wells. The main industries are food and pharmaceutical manufacturers (Koprivnica), as well as the petroleum industry (Djurdjevac). Most people work in trade (56%), service (11%), and industry (8%). Only 5% of the people are agricultural workers, with small family farms (average 0.160.24 ha). Because the food industry has been active in the area for 60 years, and the petroleum industry for more than 35 years, the county belongs among the most developed counties in Croatia, with equal and free medical care for all inhabitants. Each region has health centers. A general hospital, with approximately 400 beds, is situated in Koprivnica, about 30 km from other towns, and has existed for more than a hundred years. The hospital offers histopathology and has access to chemotherapy.21 Data Collection Data for determining the incidences of lymphohematopoietic malignancies for the three regions were obtained from the Croatian Cancer Registry of the Croatian National Institute of Public Health in Zagreb. 260 Gazdek et al. www.ijoeh.com INT J OCCUP ENVIRON HEALTH The Croatian Cancer Registry has compiled cancer incidence and mortality data since 1959 from population-based cancer registries in the whole of Croatia. Electronic data processing was introduced in 1968. Under the Statistical Research Program promulgated by the Parliament, the data are routinely collected from hospitals and inpatient reports, reports of cancer mortalities, and histology and cytology reports. Histopathologic confirmation of the diagnoses is available for 97% of lymphoma cases and more than 70% of leukemia cases. Only less than 6% of lymphohematopoietic malignancies are registered on death certificates. The cancer data include personal identification, gender, age at diagnosis, cancer site, histology, year of diagnoses, residence and education.22 The National Cancer Registry has been affiliated with the IARC since 1994, and the first published cancer-incidence data relate to the 199397 period.23 Lymphohematopoietic cancer data are classified according to the Ninth Revision of the International Classification of Diseases (ICD-9)24 and are categorized according to the latest World Health Organization classification of pathologic and genetic features of tumors of the hematopoietic and lymphoid tissues25: lymphohematopoietic malignancies (total 200208 and polycythemia vera 238.4 and idiopathic myelofibrosis 289.8), acute lymphoid leukemia (204.0), chronic lymphoid leukemia (204.1, and hairy-cell leukemia 202.4), acute myeloid leukemia (205.0, 205.3, 206.0, 207.0, and 207.2), chronic myeloid leukemia (205.1), all types of leukemia (204208 and 202.4), multiple myeloma (203), Hodgkin's lymphoma (201), non-Hodgkin's lymphoma (200 and 202 except 202.4). Statistical Analysis New cases of subtype-specific lymphohematopoietic malignancies were accumulated by sex and divided into five-year age groups (04, 59, up to 70-74, 75+) for the Djurdjevac, Koprivnica, and Krizevci regions, respectively, for two time periods: 19711980 (the period prior to oilgas exploitation) and 19812000 (the period of full oilgas exploitation). Incidence rates are expressed as new cases per 100,000 person-years and then directly age-standardized to European standard populations.26 Populations at risk were obtained by mid-period population censuses (1971, 1981, 1991, and 2001) obtained from the Central Croatian Bureau of Statistics.8 Relative risks along with 95% confidence intervals (CIs) were calculated as standardized rate ratios (SRRs) for all regions both prior to oilgas exploitation (1971 1980) and during oilgas exploitation (19812000). In addition to those measures, research also compared age-standardized rates between the different regions for the period of full oilgas exploitation (19812000). Statistically significant differences were registered as 95% CI of SRR in the studied time periods. The incidence rates in the Krizevci region were used for reference because this area does not have any oil or gas wells. RESULTS From 1971 to 2000 there were 803 new cases of lymphohematopoietic malignancies registered with the Croatian Cancer Registry. Those new cases had permanent residence in KoprivnicaKrizevci County, with 212 being registered in the Djurdjevac region, 358 in the Koprivnica region, and 233 in the Krizevci region, which does not have any oil or gas wells. Table 2 shows the incidence rates of total and individual types of lymphohematopoietic malignancies in each region for the two time periods (19711980 and 19812000). It also shows grouped data of the exposed regions for the two time periods. All three regions showed increases in total lymphohematopoietic malignancies and all subtypes of lymphohematopoietic malignancies, except non-Hodgkin's lymphoma. A decrease was seen only in the Djurdjevac region in the second time period, which is marked by oilgas exploitation. In all three regions there were statistically significant increases in total lymphohematopoietic malignancies, total leukemias, and chronic lymphoid leukemias. Furthermore, in the Djurdjevac region there was a significant ninefold increase of chronic myeloid leukemia. In the Koprivnica region acute lymphoid leukemias rose fivefold, whereas acute myeloid leukemia increased fourfold. Group data analysis of data from the exposed regions for the two time periods also showed significant increases of all lymphohematopoietic malignancies except Hodgkin's lymphoma. Increased incidences for all lymphohematopoietic malignancies and all leukemias by age were observed in both men and women for all studied regions for the period 19812000, the period of full oilgas exploitation (Figures 4 and 5). The incidences of lymphohematopoietic malignancies in particular regions for the time period of full oil gas exploitation (19812000) are shown in Table 3. Incidence rates of total leukemia, acute and chronic myeloid leukemia, chronic lymphoid leukemia, and multiple myeloma were higher in the Djurdjevac and Koprivnica regions than in the Krizevci region. Differences in the incidence rates of chronic myeloid leukemia were statistically significant, with the highest in the Djurdjevac region, and the lowest in the Krizevci region. Furthermore, significantly elevated relative risks were observed for chronic myeloid leukemia and multiple myeloma for grouped data from the exposed regions, while data analysis for the period 19711980 do not show a statistically significant difference for any lymphohematopoietic cancer. VOL 13/NO 3, JUL/SEP 2007 www.ijoeh.com Lymphohematopoietic Malignancies 261 TABLE 2 Incidences and Age-standardized Rates of Lymphohematopoietic Malignancies by Sex, Type, Regions ______________D_j_u_r_d_j_e_v_a__c__+_K__o_p_r_i_v_n_i_c_a______________ ___1_9__7_1__1_9_8__0___ ___1_9__8_1__2_0_0__0___ Rate Ratio Cases ASR Cases ASR (95%CI) ____________________D__ju__rd__je__v_a_c_____________________ ___1_9__7_1__1_9_8__0___ ___1_9__8_1__2_0_0__0___ Rate Ratio Cases ASR Cases ASR (CI) HL Pooled 18 1.7 45 2.4 1.4 9 (0.862.44) Male 9 1.8 17 1.9 1.1 6 (0.482.38) Female 9 1.6 28 3.0 1.8 3 (0.923.72) NHL Pooled 34 3.4 103 4.9 1.5 18 (1.022.11) Male 20 4.4 51 5.6 1.3 13 (0.782.10) Female 14 2.5 52 4.1 1.6 5 (0.942.82) MM Pooled 21 2.0 69 3.2 1.6 9 (1.012.47) Male 7 1.7 38 4.1 2.4 3 (1.224.66) Female 14 2.3 31 2.4 1.0 6 (0.531.93) ALL Pooled 6 0.6 25 1.5 2.5 4 (1.145.58) Male 5 1.1 17 2.2 2.0 3 (0.814.91) Female 1 0.2 8 0.9 4.3 1 (0.8422.36) CLL Pooled 12 1.2 77 3.4 2.9 5 (1.864.60) Male 10 2.3 38 4.3 1.9 4 (1.003.49) Female 2 0.4 39 2.9 8.3 1 (3.3910.09) AML Pooled 6 0.6 33 1.6 2.7 3 (1.285.55) Male 3 0.6 14 1.6 2.7 1 (0.927.66) Female 3 0.6 19 1.6 2.6 2 (0.956.94) CML Pooled 8 0.7 39 1.9 2.7 1 (1.415.05) Male 4 0.8 20 2.2 2.8 0 (1.156.91) Female 4 0.7 19 1.7 2.4 1 (0.936.15) All leukemias Pooled 46 4.5 219 10.5 2.3 19 (1.763.05) Male 32 7.1 117 13.4 1.9 13 (1.342.70) Female 14 2.5 102 8.4 3.4 6 (2.175.32) All lymphohemato poietic malignancies Pooled 124 12.0 446 21.4 1.8 57 (1.492.13) Male 71 15.6 230 25.9 1.7 36 (1.302.12) Female 53 9.3 216 18.0 1.9 21 (1.472.53) 2.2 20 3.4 1,6 (0.733.35) 1.4 5 1.8 0.6 (0.161.96) 2.2 15 5.2 3.7 (1.2410.67) 4.8 30 4.5 0.9 (0.511.70) 7.8 14 5.0 0.6 (0.291.42) 2.7 16 3.7 1.4 (0.533.68) 2.6 25 3.3 1.3 (0.602.63) 2.0 17 5.6 2.8 (1.017.62) 3.3 8 1.6 0.5 (0.141.71) 1.3 7 1.5 1.2 (0.364.13) 2.0 5 2,2 1.1 (0.264.55) 0.6 2 0.9 1.5 (0.1414.64) 1.3 30 3.7 2.9 (1.326.22) 2.6 17 5.7 2.2 (0.845.59) 0.3 13 2.6 8.7 (1.813254) 0.9 11 1.6 1.8 (0.565.63) 0.6 5 1.8 3.0 (0.4918.30) 1.1 6 1.3 1.2 (0.235.61) 0.2 15 2.1 9.7 (2.3839.78) -- 7 2.4 -- 0.4 8 1.8 4.5 (0.8926.87) 5.6 77 10.8 1.9 (1.233.03) 8.6 42 14.8 1.7 (0.983.06) 2.9 35 7.8 1.4 (1.205.06) 15.8 155 22.4 1.4 (1.061.91) 22.1 81 28.3 1.3 (0.871.88) 10.9 74 18.4 1.7 (1.072.67) ASR = age-standardized incidence rate per 100,000 person-years relative to Europe standard population; rate ratio between 19802000 and 19711980; CI = 95% confidence interval. HL = Hodgkin's lymphoma; NHL = non-Hodgkin's lymphoma; MM = multiple myeloma, ALL = acute lymphoid leukemia; CLL = chronic lymphoid leukemia; AML = acute myeloid leukemia; CML = chronic myeloid leukemia. 262 Gazdek et al. www.ijoeh.com INT J OCCUP ENVIRON HEALTH and Periods (Ages: 075 Years) _______________________K_o_p__ri_v_n_i_c_a_______________________ ____1_9_7_1___1_9_8_0____ ____1_9_8_1___2_0_0_0____ Rate Ratio Cases ASR Cases ASR (95%CI) 9 1.3 25 2.0 1.5 (0.712.98) 3 1.0 12 2.0 2.0 (0.645.96) 6 1.7 13 2.0 1.2 (0.443.05) 16 2.5 73 5.2 2.1 (1.283.28) 7 2.4 37 6.0 2.5 (1.264.86) 9 2.5 36 4.3 1.7 (0.903.40) 12 1.7 44 3.1 1.8 (1.013.19) 4 1.6 21 3.4 2.1 (0.855.18) 8 1.9 23 2.7 1.4 (0.673.10) 2 0.3 18 1.6 5.5 (1.7816.70) 2 0.6 12 2.2 3.7 (1.0111.52) 0-- 6 0.9 -- 7 1.1 47 3.2 3.0 (1.615.63) 6 2.1 21 3.6 1.7 (0.753.93) 1 0.3 26 3.0 10.0 (2.9226.91) 3 0.4 22 1.6 4.0 (1.389.01) 2 0.6 9 1.5 2.5 (0.669.22) 1 0.4 13 1.7 4.3 (1.2319.37) 7 1.0 24 1.8 1.9 (0.863.97) 4 1.2 13 2.1 1.8 (0.634.83) 3 0.8 11 1.6 2.0 (0.595.94) 27 4.0 142 10.3 2.6 (1.823.63) 19 6.3 75 12.6 2.0 (1.283.12) 8 2.2 67 8.6 3.9 (2.226.87) 67 10.0 291 20.9 2.1 (1.652.63) 35 12.1 149 24.7 2.0 (1.482.82) 32 8.6 142 17.9 2.1 (1.492.93) ________________________K_r_i_z_e_v_c_i________________________ ____1_9_7_1___1_9_8_0____ ____1_9_8_1___2_0_0_0____ Rate Ratio Cases ASR Cases ASR (CI) 11 2.5 20 2.5 1.0 (0.472.05) 6 3.0 15 4.0 1.3 (0.553.33) 5 2.2 5 1.0 0.5 (0.111.90) 14 3.3 43 4.9 1.5 (0.862.64) 10 5.8 19 5.2 0.9 (0.402.00) 4 1.6 24 4.9 3.1 (1.257.13) 5 1.2 17 1.9 1.7 (0.684.17) 0-- 9 2.5 -- 5 2.1 8 1.4 0.7 (0.212.33) 5 1.2 16 2.3 2.0 (0.815.05) 4 1.8 10 2.9 1.6 (0.544.81) 1 0.4 6 1.6 4.0 (0.6923.55) 4 0.8 21 2.4 2.9 (1.186.98) 2 1.0 12 3.3 3.3 (0.9911.27) 2 0.7 9 1.8 2.6 (0.679.38) 3 0.7 10 1.3 1.9 (0.586.08) 1 0.5 3 1.0 2.0 (0.2515.57) 2 0.7 7 1.3 1.6 (0.417.08) 2 0.5 1 0.4 1 0.5 5 0.6 1.3 (0.266.15) 3 0.7 1.8 (0.2213.97) 2 0.4 1.8 (0.079.95) 17 3.9 72 8.9 2.3 (1.463.68) 10 4.8 38 10.6 2.2 (1.184.07) 7 2.9 34 7.2 2.5 (1.244.05) 57 13.1 176 21.0 1.6 (1.212.11) 29 15.1 95 26.2 1.7 (1.192.55) 28 12.0 81 16.8 1.4 (0.922.10) VOL 13/NO 3, JUL/SEP 2007 www.ijoeh.com Lymphohematopoietic Malignancies 263 TABLE 3 Age-standardized Rates of Lymphohematopoietic Malignancies by Type and Regions, 1981-2000 (Ages: All Lymphohematopoietic Hodgkin's Non-Hodgkin's Multiple _____M__a_l_ig_n__a_n_c_i_e_s_____ _____L_y_m__p_h_o__m__a_____ _____L_y_m__p_h_o__m__a_____ ______M__y_e_l_o_m__a______ ASR Rate Ratio (CI) ASR Rate Ratio (CI) ASR Rate Ratio (CI) ASR Rate Ratio (CI) Krizevci Koprivnica Djurdjevac Djurdjevac + Koprivnica 21.0 1.0 (referent) 2.5 1,0 (referent) 4.9 1.0 (referent) 1.9 1.0 (referent) 20.9 1.0 (0.821.20) 2.0 0.8 (0.431.44) 5.2 1.1 (0.721.54) 3.1 1.6 (0.932.69) 22.4 1.1 (0.861.33) 3.4 1.4 (0.732.62) 4.5 0.9 (0.571.46) 3.3 1.7 (0.913.20) 21.4 1.0 (0.851.21) 2.4 1.0 (0.571.65) 4.9 1.0 (0.701.43) 3.2 1.6 (1.012.63) ASR = age-standardized incidence rate per 100,000 person-years relative to Europe standard population; CI = 95% confidence interval. DISCUSSION The aim of this study was to assess possible effects of exposures to crude oil and natural gas exploitation on the occurrence of lymphohematopoietic malignancies in certain regions of KoprivnicaKrizevci County. The results showed considerable increases in the incidences of chronic myeloid leukemia and multiple myeloma. Some epidemiologic studies have shown associations of the same types of lymphohematopoietic malignancies with exposures to benzene, crude oil, or petroleum refinery waste dumps.11,15,2729 Crude oil and natural gas are mixtures of many chemical compounds, mostly hydrocarbons, but also metals, nitrogen, and oxygen and sulfide compounds.10 Benzene can be found during the crude oil and natural gas production.7,30,31 Although the presence of benzene or other organic pollutants in the vicinity of oil gas fields in KoprivnicaKrizevci County has not been demonstrated (a reason could be politics of the National Petroleum Company as well as the Government32), geochemical and mineralogic assessments showed higher than normal concentrations of lead, mercury, total hydrocarbons, BTEX, and polycyclic MEN MEN WOMEN WOMEN Figure 4--Total lymphohematopoietic malignancies, incidences in regions by age group for men and women, 19812000. Figure 5--Total leukemia incidences in regions by age group in men and women, 19812000. 264 Gazdek et al. www.ijoeh.com INT J OCCUP ENVIRON HEALTH 075 Years, Sexes Combined) Acute Chronic Acute Chronic All Lymphoid Lymphoid Myeloid Myeloid _____L_e_u__k_e_m__ia__s_____ ______L_e_u_k_e__m_i_a______ ______L_e_u_k_e__m_i_a______ ______L_e_u_k_e__m_i_a______ ______L_e_u_k_e__m_i_a______ ASR Rate Ratio (CI) ASR Rate Ratio (CI) ASR Rate Ratio (CI) ASR Rate Ratio (CI) ASR Rate Ratio (CI) 8.9 1.0 (referent) 2.3 1.0 (referent) 2.4 1.0 (referent) 1.3 1.0 (referent) 0.6 1,0 (referent) 10.3 1.2 (0.871.53) 1.5 0.7 (0.331.36) 3.2 1.3 (0.822.16) 1.6 1.2 (0.592.59) 1.8 3.0 (1.407.33) 10.8 1.2 (0.871.69) 1.6 0.7 (0.281.56) 3.7 1.5 (0.882.73) 1.6 1.2 (0.533.08) 2.1 3.5 (1.3210.08) 10.5 1.2 (0.911.53) 1.5 0.7 (0.331.32) 3.4 1.4 (0.932.18) 1.6 1.3 (0.632.51) 1.9 3.4 (1.656.87) aromatic hydrocarbons in materials from two already closed pits, in spite of lime stabilization of the waste from the petroleum industry.9 Benzene is the most familiar leukemogen,10 as well as 1,3-butadiene in the tire-manufacturing industry,33 but not in petrochemical industry,34 although exposures to polycyclic aromatic hydrocarbons might be related to leukemias in children35 and esophageal, pancreatic, prostate, and lung cancers in adults.36 Exposure to benzene from oil and gas fields can occur through fume inhalation or dermal contact or by drinking water contaminated by oil.10 It is possible to contaminate the environment and people during oil and gas exploitation by exposures to large quantities of drill mud and liquid waste. Such liquid waste, together with drill mud, contains hydrocarbons and nitrogenous and sulfide compounds, as well as various metals. This waste can penetrate the surrounding soil and water, causing contamination,10 as evidenced by research that connects cancer increases in populations living near oil fields with drinking water contaminated with oil substances.19 In KoprivnicaKrizevci County, drilling wastes (drilling mud and formation water) are deposited into pits, and waterwaste is spilled directly into nearby streams. Construction of a facility for treatment of liquid waste from oilgas production will be completed in 2007.6 Inhabitants of rural areas in the Djurdjevac and Koprivnica regions (where the oilgas operations are situated) drink only well water because only towns and their surrounding areas have piped-in drinking water.21 There have been few studies of residents living near oil fields or petrochemical industries. It has been shown that living near oil fields increases the risk for total cancers as well as cancers of the stomach, rectum, skin (melanoma) and kidney.18 An increase in hematopoietic cancers in children less than 10 years old was also found.18 By contrast, a study from China did not find an association between residential petrochemical exposures and leukemia risk in children.37 However, residential petrochemical exposure was a significant risk factor for leukemia for the older age group.37 Our study showed a higher incidence rate of leukemias in children less than 10 in the unexposed region and higher incidence rates of leukemias in adults in the exposed regions. Although our study showed the strongest associations between residential oilgas exploitation exposures and chronic myeloid leukemia, as well as multiple myeloma, we could not ignore the fact that except for Hodgkin's lymphoma, all lymphohematopoietic cancers had occurred more frequently in the exposed regions since the beginning of full oilgas exploitation. All those cancers are associated with exposures to benzene or benzene-related industry.16,3840 Our data suggested that long exposure to oilgas exploitation elevates the risks for chronic myeloid leukemia and multiple myeloma. Most research done on oil and gas field workers indicates that the risk of getting myeloid leukemia, especially acute myeloid leukemia, is higher among workers who have worked in the fields for more than 30 years.11,13,14 Although there are no data on concentrations of hydrocarbons or benzene for the County, some studies have confirmed the presence of benzene in crude petroleum production or waste,7,9,30,31 while others suggest that concentrations of benzene in oil increase the occurrence of leukemia from 0.01 to 1%.10 The higher the concentration and duration of benzene exposure, the greater the risk of leukemia.12,41 Also, studies have been done on air pollution, water, soil, and vegetation used for human and animal consumption, as well as forest vegetation, in Koprivnica Krizevci County from 1990, 1995/1996 and every year since 1999.4 Those studies have monitored sulfide compounds (especially mercaptene-RSH and hydrogen sulfide) and levels of mercury, nitrate and nitrite, which were occasionally found to be higher than legally allowed, while levels of cadmium, molybdenum, cobalt, lead, zinc, copper, vanadium, chrome, and barium were below the legal maximums. Radioactive levels of uranium, radium, thorium, caesium, and natural potassium showed normal yearly variations. Although it is well known that some of the above-mentioned metals and compounds are carcinogenic,4244 no connection with hematopoietic malignancies was found in literature, nor were their effects on certain subtypes of lymphohematopoietic malignancies in KoprivnicaKrizevci County evident. VOL 13/NO 3, JUL/SEP 2007 www.ijoeh.com Lymphohematopoietic Malignancies 265 During more than 30 years of crude oil and natural gas exploitation in KoprivnicaKrizevci County, there have been a few changes in production processes that could have had adverse effects on the environment and people's health. The most important of these changes was the installation of a mercury-absorption machine and a machine for desulfurization.2,3 Those changes in production were done in order to decrease emissions of mercury and sulfuric compounds, which are not related to lymphohematopoietic malignancies.43,4547 The major limitation of the present study is that it was ecological. While reliable estimates of presumed exposures were available for the regions included, individual burdens through internal and external exposures were not considered. However, other ecological factors that need to be considered are other sources of benzene, which is mostly associated with lymphohematopoietic malignancies. Motor vehicle exhaust and tobacco smoke are other main sources of benzene. Information from the Central Croatian Bureau of Statistics showed that every second resident of Koprivnica Krizevci County has a vehicle, and there are no differences between regions.8,21 The latest smoking research (2003) showed that 28% (ratio between men and women is 1:1) in KoprivnicaKrizevci County were smokers, which is 1% more than the Croatian average. Also, differences in smoking habits between regions were not found.48 Our findings indicate evidence of a causative relationship between exposures to oilgas exploitation and increased incidences of chronic myeloid leukemia and multiple myeloma. Considering this is the first study of effects of oil and natural gas exploration on people's health in Croatia and KoprivnicaKrizevci County, further research may be useful to confirm our observations. References 1. Karasalihovic D, Maurovic L, Sunjerga S. Natural gas in Croatian energy future. Applied Energ. 2003;75:9-22. 2. Technical documentation, "Project Podravina." 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