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Khaled Kasim, Patrick Levallois, Kenneth C. Johnson, Belkacem Abdous, Pierre Auger, and the Canadian Cancer Registries Epidemiology Research Group, Chlorination Disinfection By-products in Drinking Water and the Risk of Adult Leukemia in Canada, American Journal of Epidemiology, Volume 163, Issue 2, 15 January 2006, Pages 116–126, https://doi.org/10.1093/aje/kwj020
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Abstract
The authors conducted a population-based case-control study of 1,068 incident leukemia cases and 5,039 controls aged 20–74 years during 1994–1997 to examine the association between exposure to drinking water chlorination disinfection by-products and adult leukemia risk in Canada. Residence and drinking water source histories and data from municipal water supplies were used to estimate individual chlorination disinfection by-product exposure according to water source, chlorination status, and chlorination disinfection by-product levels during the 40-year period before the interview. The analysis included 686 cases and 3,420 controls for whom water quality information was available for at least 30 of these years. Increased risk of chronic myeloid leukemia was associated with increasing years of exposure to different chlorination disinfection by-product indexes, with an adjusted odds ratio of 1.72 (95% confidence interval: 1.01, 3.08) for the highest exposure duration to total trihalomethanes of more than 40 μg/liter. In contrast, the risk of the other studied leukemia subtypes was found to decrease with increasing years of exposure to chlorination disinfection by-products. A protective effect was noted for chronic lymphoid leukemia (odds ratio = 0.60, 95 percent confidence interval: 0.41, 0.87) associated with the highest exposure duration to total trihalomethanes of more than 40 μg/liter. More studies with long-term exposure measures and large enough to evaluate leukemia subtypes are needed to further understanding of the issue.
Chlorine is the most commonly used chemical for the disinfection of Canadian water supplies (1). Chlorinated water sources serve over 75 percent of the population of Canada (2). During the chlorination process, chlorine reacts with the organic materials in water and produces a number of halogenated hydrocarbon by-products, including trihalomethanes, halogenated acetonitriles, halogenated acetic acids, haloketones, and haloaldehydes (3). As a class, the trihalomethanes are the most prevalent disinfection by-products in Canadian drinking water (1) and are routinely measured in public water supplies, making them a useful marker of the level of chlorination by-products in treated water. Since they were discovered in 1974 (4, 5), there has been considerable epidemiologic interest in the relation between the chlorination by-products in treated water and cancer incidence because of the potential public health impacts given the large populations exposed. There is some evidence that consumption of chlorinated surface water is associated with an increased risk of several types of cancer including colon (6), bladder (7), kidney (8), pancreas (9), and possibly brain (10). Recently, Villanueva et al. (11) found an odds ratio of 1.4 (95 percent confidence interval (CI): 1.2, 1.7) for bladder cancer in association with long-term consumption of chlorinated drinking water in a review of six case-control and two cohort studies conducted upon populations in Europe and North America. More recently, a pooled analysis study reported a significant increased risk of bladder cancer in association with exposure to a trihalomethane level of more than 50 μg/liter (12).
There have been few studies investigating chlorination disinfection by-products in drinking water and adult leukemia, and their results have been inconclusive. Most are ecologic in design and have relied on historical data of rather poor quality (13, 14). The loss of information through aggregation in ecologic studies and the suspected potential misclassification of exposure due to lack of individual information on long-term residence require cautious interpretation of these results (15). The objective of our population-based case-control study was to examine the relation between adult leukemia and levels of exposure to chlorination disinfection by-products, specifically total trihalomethanes and bromodichloromethane, in treated municipal drinking water by use of total lifetime residential histories and historical municipal drinking water sampling data to estimate exposure.
MATERIALS AND METHODS
Study population
We used the data available in the Canadian National Enhanced Cancer Surveillance System (NECSS) to conduct this population-based case-control study. The overall methodology for the NECSS has been described in detail elsewhere (16). The NECSS collected data on individual risk factors between 1994 and 1997 from a sample of 20,755 Canadians recently diagnosed with one of 19 types of cancer and from a sample of 5,039 population controls with age and sex distributions similar to the overall age/sex structure of the cancer cases, in eight Canadian provinces (Prince Edward Island, Nova Scotia, Manitoba, Saskatchewan, British Columbia, Alberta, Newfoundland, and Ontario).
Our study is based on all adult leukemia cases and controls participating in the NECSS. During the period 1994 through 1997, the provincial cancer registries identified 1,997 recently diagnosed and histologically confirmed adult leukemia cases, aged 20–74 years, in the eight participating Canadian provinces. Fourteen percent of the cases had died before they could be recruited, and physicians refused to give consent to contact severely ill cases (8.0 percent). In all, 1,545 cases (representing 77.4 percent of all the cases ascertained) were contacted and sent questionnaires, within 1–4 months of diagnosis. A total of 1,068 cases, representing 53.5 percent of all the cases ascertained and 70 percent of the cases contacted, completed and returned the questionnaire. Among these cases, 358 were diagnosed with acute leukemia (307 with acute myelocytic leukemia and 51 with acute lymphocytic leukemia), 643 were diagnosed with chronic leukemia (169 with chronic myelocytic leukemia, 410 with chronic lymphocytic leukemia, and 64 with hairy cell leukemia), and 67 were diagnosed with leukemia not otherwise specified.
Controls were frequency matched to the overall age/sex distribution of the 19 types of cancer included in the NECSS database. The procedures for selecting the random population-based samples of controls in each province were reported in detail in a previous report (17). In brief, the strategies used for selecting population controls varied according to the data accessibility in each province. In five provinces (Prince Edward Island, Nova Scotia, Manitoba, Saskatchewan, and British Columbia), the provincial health insurance plans were used to obtain a random sample of the provincial population stratified by age group and sex. In Ontario, the provincial Ministry of Finance property assessment database was used to obtain a stratified random sample. In Newfoundland and Alberta, random-digit dialing protocols were used to obtain population samples. In total, questionnaires were mailed to 8,060 individuals selected as potential controls in the eight provinces. In all, 5,039 controls completed and returned the questionnaires, representing 67 percent of those contacted and 63 percent of those ascertained. To maximize the power of our study, all 5,039 controls were used as a comparison group for the leukemia cases studied.
Data collection
Mailed questionnaires were used to obtain information on subjects' lifetime residential and occupational histories and on other risk factors for cancer. Telephone follow-up was attempted when necessary for clarification and completeness. The questionnaire included questions about age, gender, ethnicity, educational level, family income, height, weight, residential and job histories, active and passive smoking, alcohol use, source of drinking water, occupation, physical activity, dietary history, and occupational exposure to specific carcinogens.
Water exposure assessment
For each Canadian residence where a subject had lived for at least 1 year, the subject was asked the address, first and last year of residence, and the main source of drinking water (city water, dug well, drilled water, bottled water, or other).
The NECSS has assembled all trihalomethane monitoring data from the following information sources to create the water quality database used in this study: 1) the 1977 trihalomethane survey of 70 larger Canadian cities (18) and 2) the 1986–1995 Ontario monthly monitoring in more than 50 communities (Ontario Drinking Water Surveillance Program) for 114 treatment plants. From these data, the average levels (accounting for imbalance in sampling by season) were estimated by a linear regression model of season and plant effects (19). Other sources were 3) the provincial monitoring of trihalomethane levels in municipal water supplies, with sampling and testing conducted either by provincial authorities or by individual water treatment plants from 1990 to 1999, and 4) the Environmental Health Directorate 1993 national water-sampling data (20). The Environmental Health Directorate sampled drinking water in 51 of the largest communities across Canada. In that survey, the water samples requested were raw water and treatment plant water (after final disinfection but before distribution). The samples were collected in winter and summer when chlorination disinfection by-product levels were expected to be lowest and highest, respectively. The samples were then analyzed consistently for the chlorination disinfection by-products.
These data were then linked with the national municipal water inventories' data collected in the years 1962 (21), 1975 (22), and 1986 and 1995 (2). The national inventories were used to identify major changes in water treatment practices over time. If the treatment practices have not shown major changes over time, the average trihalomethane monitoring data were used as a measure of historical levels. When there have been major changes over time, only monitoring data prior to the changes were used. Water from private wells was assigned a trihalomethane concentration of zero because it is usually not chlorinated.
Individual exposures were assigned by linking a subject's residence and water source history to the trihalomethane data by time and geographic area. Thus, each subject would have, for each year of residence in the study period, indicators of exposures of interest (source of water supply, chlorination status, and trihalomethane levels). Duration-of-exposure estimates were computed for each subject by summing the number of years in each exposure category. The study analyses considered only exposures occurring over the 40-year period preceding the subject's interview. To reduce the level of misclassification in exposures, these analyses are restricted to subjects with 30 or more years of known water history during the targeted 40-year period. Subjects who reported no exposure to chlorinated surface water during the studied period were used as a referent group. The years of exposure to chlorinated water were categorized into tertiles according to the distribution observed in the study controls. We examined the risk of adult leukemia by the total years of exposure to chlorinated surface water and by the total years of exposure to water with an estimated total trihalomethane level of more than 20 and 40 μg/liter and to water with an estimated bromodichloromethane level of more than 5 μg/liter.
Among subjects exposed only to chlorinated water sources during the 40-year exposure period (419 cases and 2,106 controls), we also examined the risk of adult leukemia by different estimated levels of total trihalomethanes and bromodichloromethane. Moreover, we examined the effect of the quantity of water ingested on the risk of adult leukemia stratified by different estimated levels of total trihalomethanes. We combined the studied water exposure factors with questionnaire responses regarding daily tap water and total fluid consumptions for the 2-year period before the interview. Total daily tap water consumption was calculated by summing the daily fluid volume of glasses of water (8 ounces (230 ml)), cups of coffee and tea (6 ounces (173 ml)), and glasses of reconstituted juice (4 ounces (115 ml)). Water consumption was categorized into three levels based on the tertile distribution among study controls. The referent category for all risk estimates comprised those who reported consuming less than 1 liter per day.
Confounding factors
On the basis of the leukemia literature (23–25) and the data available in the NECSS questionnaire, the following covariates were included in the study analyses to explore their confounding effects: age (continuous); gender (male vs. female); ethnicity (Western European descent, African descent, and others); family income (low, middle, and high); educational years (≤9, 10–15, and >15 years); residence (average proportion of time living in urban areas as a continuous variable); body mass index (<25, 25–<30, and ≥30 kg/m2); total years of passive smoking (quartiles); smoking status (never smoker, former smoker, current smoker); and pack-years of smoking (0, 1–10, 11–20, >20). “Never smokers” were defined as those who reported never smoking or smoking less than 100 cigarettes in their lifetime. “Former smokers” were defined as those subjects who reported stopping smoking at least 1 year before the date of interview. In addition, we adjusted for occupational exposure to benzene and to ionizing radiation (exposed vs. never exposed). In the NECSS database, the occupational history of each included subject was coded to Canadian 1980 Standard Industrial Codes and Canadian 1980 Standard Occupational Codes, with the coding done without coder knowledge of case or control status. By use of Canadian 1980 Standard Occupational Codes, we linked our study data with a database derived from Montreal occupational studies (26) to build up a simple job exposure matrix for benzene and ionizing radiation exposures. By use of this job exposure matrix, subjects with no and/or possible job exposure probability were combined as nonexposed, while those with probable or certain job exposure probability were combined as exposed. Subjects with occupational codes not addressed in the Montreal studies or with missed codes were evaluated on the basis of their reported job titles into ever and never exposed by one of the authors (P. A.) and an occupational hygienist without any knowledge of case or control status.
Statistical analysis
We analyzed the collected data by use of an SAS software package (27). When comparing the distribution of demographic and confounding factors between study controls and each of the studied leukemia subtypes, we used χ2 tests for the categorical variables and the t test for continuous variables. Odds ratios and 95 percent confidence intervals for various associations were determined with unconditional logistic regression models (28) while controlling for the possible covariates. The potential confounding variables considered in this study were age, gender, ethnic group, education, residence, body mass index, total years of passive smoking, smoking status, pack-years of smoking, and occupational exposure to benzene and to ionizing radiation. To select the factors to be included in each model, we used an initial stepwise regression with a p value of 0.10 as entry criterion and a p value of 0.15 as exclusion criterion. Accordingly, we adjusted the final models by the selected subset of the variables above. In addition, we retained in final models those variables known to be biologically important in adult leukemia development (age and occupational exposure to benzene and ionizing radiation). Because of substantial gender differences in our study cases and controls, we also retained this variable in all final models. Tests for trend were based on a likelihood-ratio test conducted by assigning an ordinal value to each level of a categorical variable and treating the variable by its given ordinal values in a logistic regression model.
RESULTS
Of the 1,068 incident and histologically confirmed adult leukemia cases and 5,039 population controls included in the NECSS database, we selected cases and controls who reported residences in Canada for at least 30 years of the 40-year study exposure period. This restricted database included 686 adult leukemia cases (64.2 percent of all case respondents), 421 males (65.7 percent), and 265 females (62.0 percent), as well as 3,240 controls (64.3 percent of all control respondents), 1,660 males (64.6 percent), and 1,580 females (64.0 percent). Of the 686 cases included, there were 161 acute myelocytic leukemia cases, 23 acute lymphocytic leukemia cases, 91 chronic myelocytic leukemia cases, 323 chronic lymphocytic leukemia cases, and 48 hairy cell leukemia cases.
Table 1 shows the characteristics of the included adult leukemia cases and population controls. The leukemia cases were slightly older than were the controls. Acute lymphocytic leukemia cases tended to be younger, and the chronic lymphocytic leukemia participants tended to be older than other cases. Furthermore, adult leukemia cases tended to be more frequently obese, occupationally exposed to benzene (except those with acute lymphocytic leukemia) and ionizing radiation (except those with chronic lymphocytic leukemia and hairy cell leukemia), and more exposed to environmental tobacco smoke (except those with acute myelocytic leukemia, acute lymphocytic leukemia, and hairy cell leukemia). The percentage of cases in the highest income tertile was higher compared with the percentage of controls in the highest income tertile, with the exception of cases with acute myelocytic leukemia and chronic myelocytic leukemia.
Characteristics* . | Controls (n = 3,240) . | All leukemia† (n = 686) . | AML‡ (n = 161) . | ALL‡ (n = 23) . | CML‡ (n = 91) . | CLL‡ (n = 323) . | HCL‡ (n = 48) . |
---|---|---|---|---|---|---|---|
Age (years), mean (SD‡) | 61 (10.2) | 62 (9.6) | 60 (10.6) | 57 (9.6) | 59 (10.7) | 64 (8.2) | 58 (9.9) |
Gender, no. (%) of group | |||||||
Male | 1,580 (49) | 421 (61) | 90 (56) | 13 (56) | 48 (53) | 217 (67) | 34 (71) |
Female | 1,660 (51) | 265 (39) | 71 (44) | 10 (44) | 43 (47) | 106 (33) | 14 (29) |
Ethnic group, no. (%) of group | |||||||
European descent | 2,973 (92) | 614 (90) | 142 (88) | 21 (91) | 81 (89) | 291 (90) | 43 (90) |
African descent | 4 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Other descent | 263 (8) | 72 (10) | 19 (12) | 2 (9) | 10 (11) | 32 (10) | 5 (10) |
Family income (Can$/year), no. (%) of group | |||||||
High | 521 (16) | 119 (17) | 16 (10) | 5 (22) | 12 (13) | 66 (20) | 17 (35) |
Middle | 1,370 (42) | 290 (42) | 81 (50) | 8 (35) | 46 (51) | 125 (39) | 13 (27) |
Low | 507 (16) | 99 (14) | 18 (11) | 4 (17) | 11 (12) | 51 (16) | 11 (23) |
Missing | 842 (26) | 178 (26) | 46 (29) | 6 (26) | 22 (24) | 81 (25) | 7 (15) |
Educational level (years), mean (SD) | 12 (3.6) | 11 (3.4) | 12 (3.5) | 12 (3.6) | 11 (3.4) | 11 (3.3) | 11 (3.3) |
Occupational exposure to benzene, no. (%) of group | |||||||
Yes | 271 (8) | 83 (12) | 17 (11) | 2 (9) | 16 (18) | 38 (12) | 6 (12) |
No | 2,969 (92) | 603 (88) | 144 (89) | 21 (91) | 75 (82) | 285 (88) | 42 (88) |
Occupational exposure to ionizing radiation, no. (%) of group | |||||||
Yes | 114 (4) | 35 (5) | 9 (6) | 2 (9) | 7 (8) | 14 (4) | 1 (2) |
No | 3,126 (96) | 651 (95) | 152 (94) | 21 (91) | 84 (92) | 309 (96) | 47 (98) |
Smoking status, no. (%) of group | |||||||
Never smoked | 1,134 (35) | 225 (33) | 51 (32) | 14 (61) | 24 (26) | 108 (33) | 19 (40) |
Former smoker | 1,429 (44) | 330 (48) | 77 (48) | 8 (35) | 49 (54) | 153 (47) | 22 (46) |
Current smoker | 677 (21) | 131 (19) | 33 (21) | 1 (4) | 18 (20) | 62 (20) | 7 (15) |
Pack-years of smoking, no. (%) of group | |||||||
Never | 1,134 (35) | 225 (33) | 51 (32) | 14 (61) | 24 (26) | 108 (33) | 19 (40) |
1–10 | 662 (20) | 129 (19) | 23 (14) | 4 (17) | 22 (24) | 60 (19) | 14 (29) |
11–20 | 509 (16) | 117 (17) | 30 (19) | 3 (13) | 18 (20) | 55 (17) | 6 (13) |
>20 | 906 (28) | 211 (31) | 55 (34) | 2 (9) | 27 (30) | 98 (30) | 9 (19) |
Missing§ | 29 (1) | 4 (1) | 2 (1) | 2 (1) | |||
Body mass index (kg/m2), no. (%) of group | |||||||
<25 | 1,429 (44) | 253 (37) | 63 (39) | 7 (30) | 32 (35) | 118 (37) | 16 (33) |
25–<30 | 1,305 (40) | 288 (42) | 63 (39) | 9 (39) | 30 (33) | 144 (45) | 24 (50) |
≥30 | 506 (16) | 145 (21) | 35 (22) | 7 (30) | 29 (32) | 61 (19) | 8 (17) |
Total years of passive smoking, mean (SD) | 53 (33.7) | 57 (33.7) | 55 (32.3) | 43 (38.4) | 55 (30.7) | 61 (34.2) | 52 (33.8) |
Average proportion of time living in urban area, mean (SD) | 0.71 (0.3) | 0.69 (0.3) | 0.70 (0.3) | 0.63 (0.4) | 0.76 (0.3) | 0.67 (0.3) | 0.63 (0.4) |
Characteristics* . | Controls (n = 3,240) . | All leukemia† (n = 686) . | AML‡ (n = 161) . | ALL‡ (n = 23) . | CML‡ (n = 91) . | CLL‡ (n = 323) . | HCL‡ (n = 48) . |
---|---|---|---|---|---|---|---|
Age (years), mean (SD‡) | 61 (10.2) | 62 (9.6) | 60 (10.6) | 57 (9.6) | 59 (10.7) | 64 (8.2) | 58 (9.9) |
Gender, no. (%) of group | |||||||
Male | 1,580 (49) | 421 (61) | 90 (56) | 13 (56) | 48 (53) | 217 (67) | 34 (71) |
Female | 1,660 (51) | 265 (39) | 71 (44) | 10 (44) | 43 (47) | 106 (33) | 14 (29) |
Ethnic group, no. (%) of group | |||||||
European descent | 2,973 (92) | 614 (90) | 142 (88) | 21 (91) | 81 (89) | 291 (90) | 43 (90) |
African descent | 4 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Other descent | 263 (8) | 72 (10) | 19 (12) | 2 (9) | 10 (11) | 32 (10) | 5 (10) |
Family income (Can$/year), no. (%) of group | |||||||
High | 521 (16) | 119 (17) | 16 (10) | 5 (22) | 12 (13) | 66 (20) | 17 (35) |
Middle | 1,370 (42) | 290 (42) | 81 (50) | 8 (35) | 46 (51) | 125 (39) | 13 (27) |
Low | 507 (16) | 99 (14) | 18 (11) | 4 (17) | 11 (12) | 51 (16) | 11 (23) |
Missing | 842 (26) | 178 (26) | 46 (29) | 6 (26) | 22 (24) | 81 (25) | 7 (15) |
Educational level (years), mean (SD) | 12 (3.6) | 11 (3.4) | 12 (3.5) | 12 (3.6) | 11 (3.4) | 11 (3.3) | 11 (3.3) |
Occupational exposure to benzene, no. (%) of group | |||||||
Yes | 271 (8) | 83 (12) | 17 (11) | 2 (9) | 16 (18) | 38 (12) | 6 (12) |
No | 2,969 (92) | 603 (88) | 144 (89) | 21 (91) | 75 (82) | 285 (88) | 42 (88) |
Occupational exposure to ionizing radiation, no. (%) of group | |||||||
Yes | 114 (4) | 35 (5) | 9 (6) | 2 (9) | 7 (8) | 14 (4) | 1 (2) |
No | 3,126 (96) | 651 (95) | 152 (94) | 21 (91) | 84 (92) | 309 (96) | 47 (98) |
Smoking status, no. (%) of group | |||||||
Never smoked | 1,134 (35) | 225 (33) | 51 (32) | 14 (61) | 24 (26) | 108 (33) | 19 (40) |
Former smoker | 1,429 (44) | 330 (48) | 77 (48) | 8 (35) | 49 (54) | 153 (47) | 22 (46) |
Current smoker | 677 (21) | 131 (19) | 33 (21) | 1 (4) | 18 (20) | 62 (20) | 7 (15) |
Pack-years of smoking, no. (%) of group | |||||||
Never | 1,134 (35) | 225 (33) | 51 (32) | 14 (61) | 24 (26) | 108 (33) | 19 (40) |
1–10 | 662 (20) | 129 (19) | 23 (14) | 4 (17) | 22 (24) | 60 (19) | 14 (29) |
11–20 | 509 (16) | 117 (17) | 30 (19) | 3 (13) | 18 (20) | 55 (17) | 6 (13) |
>20 | 906 (28) | 211 (31) | 55 (34) | 2 (9) | 27 (30) | 98 (30) | 9 (19) |
Missing§ | 29 (1) | 4 (1) | 2 (1) | 2 (1) | |||
Body mass index (kg/m2), no. (%) of group | |||||||
<25 | 1,429 (44) | 253 (37) | 63 (39) | 7 (30) | 32 (35) | 118 (37) | 16 (33) |
25–<30 | 1,305 (40) | 288 (42) | 63 (39) | 9 (39) | 30 (33) | 144 (45) | 24 (50) |
≥30 | 506 (16) | 145 (21) | 35 (22) | 7 (30) | 29 (32) | 61 (19) | 8 (17) |
Total years of passive smoking, mean (SD) | 53 (33.7) | 57 (33.7) | 55 (32.3) | 43 (38.4) | 55 (30.7) | 61 (34.2) | 52 (33.8) |
Average proportion of time living in urban area, mean (SD) | 0.71 (0.3) | 0.69 (0.3) | 0.70 (0.3) | 0.63 (0.4) | 0.76 (0.3) | 0.67 (0.3) | 0.63 (0.4) |
Percentages are presented by their round.
“All leukemia” included leukemia not otherwise specified as cases.
AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; CML, chronic myelocytic leukemia; CLL, chronic lymphocytic leukemia; HCL, hairy cell leukemia; SD, standard deviation.
Missing is due to missing data either for a time or quantity.
Characteristics* . | Controls (n = 3,240) . | All leukemia† (n = 686) . | AML‡ (n = 161) . | ALL‡ (n = 23) . | CML‡ (n = 91) . | CLL‡ (n = 323) . | HCL‡ (n = 48) . |
---|---|---|---|---|---|---|---|
Age (years), mean (SD‡) | 61 (10.2) | 62 (9.6) | 60 (10.6) | 57 (9.6) | 59 (10.7) | 64 (8.2) | 58 (9.9) |
Gender, no. (%) of group | |||||||
Male | 1,580 (49) | 421 (61) | 90 (56) | 13 (56) | 48 (53) | 217 (67) | 34 (71) |
Female | 1,660 (51) | 265 (39) | 71 (44) | 10 (44) | 43 (47) | 106 (33) | 14 (29) |
Ethnic group, no. (%) of group | |||||||
European descent | 2,973 (92) | 614 (90) | 142 (88) | 21 (91) | 81 (89) | 291 (90) | 43 (90) |
African descent | 4 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Other descent | 263 (8) | 72 (10) | 19 (12) | 2 (9) | 10 (11) | 32 (10) | 5 (10) |
Family income (Can$/year), no. (%) of group | |||||||
High | 521 (16) | 119 (17) | 16 (10) | 5 (22) | 12 (13) | 66 (20) | 17 (35) |
Middle | 1,370 (42) | 290 (42) | 81 (50) | 8 (35) | 46 (51) | 125 (39) | 13 (27) |
Low | 507 (16) | 99 (14) | 18 (11) | 4 (17) | 11 (12) | 51 (16) | 11 (23) |
Missing | 842 (26) | 178 (26) | 46 (29) | 6 (26) | 22 (24) | 81 (25) | 7 (15) |
Educational level (years), mean (SD) | 12 (3.6) | 11 (3.4) | 12 (3.5) | 12 (3.6) | 11 (3.4) | 11 (3.3) | 11 (3.3) |
Occupational exposure to benzene, no. (%) of group | |||||||
Yes | 271 (8) | 83 (12) | 17 (11) | 2 (9) | 16 (18) | 38 (12) | 6 (12) |
No | 2,969 (92) | 603 (88) | 144 (89) | 21 (91) | 75 (82) | 285 (88) | 42 (88) |
Occupational exposure to ionizing radiation, no. (%) of group | |||||||
Yes | 114 (4) | 35 (5) | 9 (6) | 2 (9) | 7 (8) | 14 (4) | 1 (2) |
No | 3,126 (96) | 651 (95) | 152 (94) | 21 (91) | 84 (92) | 309 (96) | 47 (98) |
Smoking status, no. (%) of group | |||||||
Never smoked | 1,134 (35) | 225 (33) | 51 (32) | 14 (61) | 24 (26) | 108 (33) | 19 (40) |
Former smoker | 1,429 (44) | 330 (48) | 77 (48) | 8 (35) | 49 (54) | 153 (47) | 22 (46) |
Current smoker | 677 (21) | 131 (19) | 33 (21) | 1 (4) | 18 (20) | 62 (20) | 7 (15) |
Pack-years of smoking, no. (%) of group | |||||||
Never | 1,134 (35) | 225 (33) | 51 (32) | 14 (61) | 24 (26) | 108 (33) | 19 (40) |
1–10 | 662 (20) | 129 (19) | 23 (14) | 4 (17) | 22 (24) | 60 (19) | 14 (29) |
11–20 | 509 (16) | 117 (17) | 30 (19) | 3 (13) | 18 (20) | 55 (17) | 6 (13) |
>20 | 906 (28) | 211 (31) | 55 (34) | 2 (9) | 27 (30) | 98 (30) | 9 (19) |
Missing§ | 29 (1) | 4 (1) | 2 (1) | 2 (1) | |||
Body mass index (kg/m2), no. (%) of group | |||||||
<25 | 1,429 (44) | 253 (37) | 63 (39) | 7 (30) | 32 (35) | 118 (37) | 16 (33) |
25–<30 | 1,305 (40) | 288 (42) | 63 (39) | 9 (39) | 30 (33) | 144 (45) | 24 (50) |
≥30 | 506 (16) | 145 (21) | 35 (22) | 7 (30) | 29 (32) | 61 (19) | 8 (17) |
Total years of passive smoking, mean (SD) | 53 (33.7) | 57 (33.7) | 55 (32.3) | 43 (38.4) | 55 (30.7) | 61 (34.2) | 52 (33.8) |
Average proportion of time living in urban area, mean (SD) | 0.71 (0.3) | 0.69 (0.3) | 0.70 (0.3) | 0.63 (0.4) | 0.76 (0.3) | 0.67 (0.3) | 0.63 (0.4) |
Characteristics* . | Controls (n = 3,240) . | All leukemia† (n = 686) . | AML‡ (n = 161) . | ALL‡ (n = 23) . | CML‡ (n = 91) . | CLL‡ (n = 323) . | HCL‡ (n = 48) . |
---|---|---|---|---|---|---|---|
Age (years), mean (SD‡) | 61 (10.2) | 62 (9.6) | 60 (10.6) | 57 (9.6) | 59 (10.7) | 64 (8.2) | 58 (9.9) |
Gender, no. (%) of group | |||||||
Male | 1,580 (49) | 421 (61) | 90 (56) | 13 (56) | 48 (53) | 217 (67) | 34 (71) |
Female | 1,660 (51) | 265 (39) | 71 (44) | 10 (44) | 43 (47) | 106 (33) | 14 (29) |
Ethnic group, no. (%) of group | |||||||
European descent | 2,973 (92) | 614 (90) | 142 (88) | 21 (91) | 81 (89) | 291 (90) | 43 (90) |
African descent | 4 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Other descent | 263 (8) | 72 (10) | 19 (12) | 2 (9) | 10 (11) | 32 (10) | 5 (10) |
Family income (Can$/year), no. (%) of group | |||||||
High | 521 (16) | 119 (17) | 16 (10) | 5 (22) | 12 (13) | 66 (20) | 17 (35) |
Middle | 1,370 (42) | 290 (42) | 81 (50) | 8 (35) | 46 (51) | 125 (39) | 13 (27) |
Low | 507 (16) | 99 (14) | 18 (11) | 4 (17) | 11 (12) | 51 (16) | 11 (23) |
Missing | 842 (26) | 178 (26) | 46 (29) | 6 (26) | 22 (24) | 81 (25) | 7 (15) |
Educational level (years), mean (SD) | 12 (3.6) | 11 (3.4) | 12 (3.5) | 12 (3.6) | 11 (3.4) | 11 (3.3) | 11 (3.3) |
Occupational exposure to benzene, no. (%) of group | |||||||
Yes | 271 (8) | 83 (12) | 17 (11) | 2 (9) | 16 (18) | 38 (12) | 6 (12) |
No | 2,969 (92) | 603 (88) | 144 (89) | 21 (91) | 75 (82) | 285 (88) | 42 (88) |
Occupational exposure to ionizing radiation, no. (%) of group | |||||||
Yes | 114 (4) | 35 (5) | 9 (6) | 2 (9) | 7 (8) | 14 (4) | 1 (2) |
No | 3,126 (96) | 651 (95) | 152 (94) | 21 (91) | 84 (92) | 309 (96) | 47 (98) |
Smoking status, no. (%) of group | |||||||
Never smoked | 1,134 (35) | 225 (33) | 51 (32) | 14 (61) | 24 (26) | 108 (33) | 19 (40) |
Former smoker | 1,429 (44) | 330 (48) | 77 (48) | 8 (35) | 49 (54) | 153 (47) | 22 (46) |
Current smoker | 677 (21) | 131 (19) | 33 (21) | 1 (4) | 18 (20) | 62 (20) | 7 (15) |
Pack-years of smoking, no. (%) of group | |||||||
Never | 1,134 (35) | 225 (33) | 51 (32) | 14 (61) | 24 (26) | 108 (33) | 19 (40) |
1–10 | 662 (20) | 129 (19) | 23 (14) | 4 (17) | 22 (24) | 60 (19) | 14 (29) |
11–20 | 509 (16) | 117 (17) | 30 (19) | 3 (13) | 18 (20) | 55 (17) | 6 (13) |
>20 | 906 (28) | 211 (31) | 55 (34) | 2 (9) | 27 (30) | 98 (30) | 9 (19) |
Missing§ | 29 (1) | 4 (1) | 2 (1) | 2 (1) | |||
Body mass index (kg/m2), no. (%) of group | |||||||
<25 | 1,429 (44) | 253 (37) | 63 (39) | 7 (30) | 32 (35) | 118 (37) | 16 (33) |
25–<30 | 1,305 (40) | 288 (42) | 63 (39) | 9 (39) | 30 (33) | 144 (45) | 24 (50) |
≥30 | 506 (16) | 145 (21) | 35 (22) | 7 (30) | 29 (32) | 61 (19) | 8 (17) |
Total years of passive smoking, mean (SD) | 53 (33.7) | 57 (33.7) | 55 (32.3) | 43 (38.4) | 55 (30.7) | 61 (34.2) | 52 (33.8) |
Average proportion of time living in urban area, mean (SD) | 0.71 (0.3) | 0.69 (0.3) | 0.70 (0.3) | 0.63 (0.4) | 0.76 (0.3) | 0.67 (0.3) | 0.63 (0.4) |
Percentages are presented by their round.
“All leukemia” included leukemia not otherwise specified as cases.
AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; CML, chronic myelocytic leukemia; CLL, chronic lymphocytic leukemia; HCL, hairy cell leukemia; SD, standard deviation.
Missing is due to missing data either for a time or quantity.
Table 2 presents the adjusted odds ratios of adult leukemia by the duration of exposure to chlorinated surface water. The risk of adult leukemia was found to vary according to the studied leukemia subtypes. In a comparison of subjects never exposed to chlorinated surface water over the 40-year period studied, we found the risk of chronic myelocytic leukemia to increase with increasing years of exposure, with an adjusted odds ratio of 2.20 (95 percent CI: 0.93, 5.23) among subjects reporting exposure to chlorinated surface water for 36 or more years. For all leukemias combined as well as other studied leukemia subtypes, we did not find clear associations with the duration of exposure to chlorinated surface water, although the risk was found to decrease by increasing exposure years for most of the leukemia subtypes. Repeating these analyses while excluding the last 5 years of exposure preceding the date of diagnosis for cases and the time of interview for controls, as a hypothesized latency period for adult leukemia, we did not find substantial differences from these presented results (data not shown).
Duration of exposure to chlorinated surface water† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
Never exposed | 466 | 102 | 1.00 | 18 | 1.00 | 7 | 1.00 | 7 | 1.00 | 53 | 1.00 | 13 | 1.00 | ||||||
1–28 years | 933 | 219 | 1.15 (0.88, 1.51) | 53 | 1.48 (0.85, 2.59) | 6 | 0.44 (0.14, 1.35) | 28 | 1.86 (0.79, 4.36) | 100 | 1.10 (0.77, 1.59) | 17 | 0.67 (0.31, 1.41) | ||||||
29–35 years | 1,045 | 223 | 1.02 (0.78, 1.34) | 58 | 1.45 (0.84, 2.50) | 7 | 0.46 (0.16, 1.36) | 33 | 2.14 (0.92, 4.94) | 103 | 0.92 (0.64, 1.31) | 10 | 0.34 (0.15, 0.79) | ||||||
≥36 years | 796 | 142 | 0.84 (0.63, 1.12) | 32 | 1.09 (0.60, 1.97) | 3 | 0.31 (0.08, 1.23) | 23 | 2.20 (0.93, 5.23) | 67 | 0.69 (0.47, 1.02) | 8 | 0.44 (0.18, 1.08) | ||||||
ptrend | 0.07 | 0.93 | 0.10 | 0.09 | 0.02 | 0.02 |
Duration of exposure to chlorinated surface water† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
Never exposed | 466 | 102 | 1.00 | 18 | 1.00 | 7 | 1.00 | 7 | 1.00 | 53 | 1.00 | 13 | 1.00 | ||||||
1–28 years | 933 | 219 | 1.15 (0.88, 1.51) | 53 | 1.48 (0.85, 2.59) | 6 | 0.44 (0.14, 1.35) | 28 | 1.86 (0.79, 4.36) | 100 | 1.10 (0.77, 1.59) | 17 | 0.67 (0.31, 1.41) | ||||||
29–35 years | 1,045 | 223 | 1.02 (0.78, 1.34) | 58 | 1.45 (0.84, 2.50) | 7 | 0.46 (0.16, 1.36) | 33 | 2.14 (0.92, 4.94) | 103 | 0.92 (0.64, 1.31) | 10 | 0.34 (0.15, 0.79) | ||||||
≥36 years | 796 | 142 | 0.84 (0.63, 1.12) | 32 | 1.09 (0.60, 1.97) | 3 | 0.31 (0.08, 1.23) | 23 | 2.20 (0.93, 5.23) | 67 | 0.69 (0.47, 1.02) | 8 | 0.44 (0.18, 1.08) | ||||||
ptrend | 0.07 | 0.93 | 0.10 | 0.09 | 0.02 | 0.02 |
All odds ratios were adjusted for age, gender, and occupational exposure to benzene and ionizing radiation. Odds ratios were also adjusted for body mass index (all leukemia, AML, ALL, CML, CLL); passive smoking (all leukemia, AML, CLL); pack-years of smoking (AML, ALL, HCL); and education (all leukemia and CML).
Calculated over the 40 years before the interview for subjects with 30 or more years (75%) of known water history.
“All leukemia” included leukemia not otherwise specified as cases.
AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; CML, chronic myelocytic leukemia; CLL, chronic lymphocytic leukemia; HCL, hairy cell leukemia; OR, odds ratio; CI, confidence interval.
Duration of exposure to chlorinated surface water† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
Never exposed | 466 | 102 | 1.00 | 18 | 1.00 | 7 | 1.00 | 7 | 1.00 | 53 | 1.00 | 13 | 1.00 | ||||||
1–28 years | 933 | 219 | 1.15 (0.88, 1.51) | 53 | 1.48 (0.85, 2.59) | 6 | 0.44 (0.14, 1.35) | 28 | 1.86 (0.79, 4.36) | 100 | 1.10 (0.77, 1.59) | 17 | 0.67 (0.31, 1.41) | ||||||
29–35 years | 1,045 | 223 | 1.02 (0.78, 1.34) | 58 | 1.45 (0.84, 2.50) | 7 | 0.46 (0.16, 1.36) | 33 | 2.14 (0.92, 4.94) | 103 | 0.92 (0.64, 1.31) | 10 | 0.34 (0.15, 0.79) | ||||||
≥36 years | 796 | 142 | 0.84 (0.63, 1.12) | 32 | 1.09 (0.60, 1.97) | 3 | 0.31 (0.08, 1.23) | 23 | 2.20 (0.93, 5.23) | 67 | 0.69 (0.47, 1.02) | 8 | 0.44 (0.18, 1.08) | ||||||
ptrend | 0.07 | 0.93 | 0.10 | 0.09 | 0.02 | 0.02 |
Duration of exposure to chlorinated surface water† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
Never exposed | 466 | 102 | 1.00 | 18 | 1.00 | 7 | 1.00 | 7 | 1.00 | 53 | 1.00 | 13 | 1.00 | ||||||
1–28 years | 933 | 219 | 1.15 (0.88, 1.51) | 53 | 1.48 (0.85, 2.59) | 6 | 0.44 (0.14, 1.35) | 28 | 1.86 (0.79, 4.36) | 100 | 1.10 (0.77, 1.59) | 17 | 0.67 (0.31, 1.41) | ||||||
29–35 years | 1,045 | 223 | 1.02 (0.78, 1.34) | 58 | 1.45 (0.84, 2.50) | 7 | 0.46 (0.16, 1.36) | 33 | 2.14 (0.92, 4.94) | 103 | 0.92 (0.64, 1.31) | 10 | 0.34 (0.15, 0.79) | ||||||
≥36 years | 796 | 142 | 0.84 (0.63, 1.12) | 32 | 1.09 (0.60, 1.97) | 3 | 0.31 (0.08, 1.23) | 23 | 2.20 (0.93, 5.23) | 67 | 0.69 (0.47, 1.02) | 8 | 0.44 (0.18, 1.08) | ||||||
ptrend | 0.07 | 0.93 | 0.10 | 0.09 | 0.02 | 0.02 |
All odds ratios were adjusted for age, gender, and occupational exposure to benzene and ionizing radiation. Odds ratios were also adjusted for body mass index (all leukemia, AML, ALL, CML, CLL); passive smoking (all leukemia, AML, CLL); pack-years of smoking (AML, ALL, HCL); and education (all leukemia and CML).
Calculated over the 40 years before the interview for subjects with 30 or more years (75%) of known water history.
“All leukemia” included leukemia not otherwise specified as cases.
AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; CML, chronic myelocytic leukemia; CLL, chronic lymphocytic leukemia; HCL, hairy cell leukemia; OR, odds ratio; CI, confidence interval.
Table 3 shows the risk estimates for adult leukemia associated with years of exposure to estimated total trihalomethane and bromodichloromethane levels. Increasing years of exposure to total trihalomethane levels of more than 20 and 40 μg/liter and to a bromodichloromethane level of more than 5 μg/liter were associated with increased risks of chronic myelocytic leukemia. The adjusted odds ratio for chronic myelocytic leukemia with the highest exposure duration was 1.70 (95 percent CI: 1.00, 3.03) for a total trihalomethane level of more than 20 μg/liter, 1.72 (95 percent CI: 1.01, 3.08) for a total trihalomethane level of more than 40 μg/liter, and 1.63 (95 percent CI: 1.00, 3.10) for a bromodichloromethane level of more than 5 μg/liter. When we carried out stratified analysis by gender, we found that the risk of chronic myelocytic leukemia associated with total trihalomethanes was not different (data not shown).
Water factor level and years of exposure† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
TTHM§ (>20 μg/liter) | |||||||||||||||||||
Never | 1,435 | 333 | 1.00 | 71 | 1.00 | 10 | 1.00 | 33 | 1.00 | 174 | 1.00 | 25 | 1.00 | ||||||
1–11 | 548 | 115 | 0.94 (0.73, 1.19) | 26 | 0.94 (0.59, 1.50) | 5 | 1.26 (0.42, 3.77) | 16 | 1.13 (0.61, 2.09) | 50 | 0.82 (0.58, 1.14) | 10 | 1.04 (0.50, 2.20) | ||||||
12–31 | 680 | 145 | 0.93 (0.75, 1.16) | 36 | 1.06 (0.70, 1.61) | 6 | 1.23 (0.44, 3.44) | 22 | 1.32 (0.76, 2.30) | 63 | 0.80 (0.62, 1.10) | 11 | 0.89 (0.43, 1.84) | ||||||
>31 | 577 | 93 | 0.70 (0.55, 0.91) | 28 | 1.03 (0.66, 1.62) | 2 | 0.63 (0.14, 2.91) | 20 | 1.70 (1.00, 3.03) | 36 | 0.47 (0.32, 0.68) | 2 | 0.22 (0.05, 0.92) | ||||||
ptrend | 0.03 | 0.93 | 0.61 | 0.11 | 0.001 | 0.05 | |||||||||||||
TTHM (>40 μg/liter) | |||||||||||||||||||
Never | 1,793 | 392 | 1.00 | 84 | 1.00 | 13 | 1.00 | 40 | 1.00 | 200 | 1.00 | 30 | 1.00 | ||||||
1–11 | 503 | 104 | 0.97 (0.76, 1.24) | 26 | 1.10 (0.70, 1.73) | 4 | 1.07 (0.34, 3.34) | 16 | 1.32 (0.73, 2.41) | 43 | 0.81 (0.57, 1.15) | 8 | 0.96 (0.43, 2.08) | ||||||
12–31 | 492 | 113 | 1.06 (0.84, 1.35) | 26 | 1.11 (0.70, 1.74) | 4 | 1.04 (0.33, 3.24) | 20 | 1.70 (0.97, 3.03) | 46 | 0.87 (0.62, 1.23) | 10 | 1.17 (0.57, 2.43) | ||||||
>31 | 452 | 77 | 0.77 (0.59, 1.02) | 25 | 1.23 (0.78, 1.96) | 2 | 0.76 (0.17, 3.44) | 14 | 1.72 (1.01, 3.08) | 34 | 0.60 (0.41, 0.87) | 0 | 0.00 | ||||||
ptrend | 0.20 | 0.42 | 0.68 | 0.05 | 0.03 | 0.08 | |||||||||||||
BDCM§ (>5 μg/liter) | |||||||||||||||||||
Never | 2,283 | 478 | 1.00 | 114 | 1.00 | 17 | 1.00 | 58 | 1.00 | 228 | 1.00 | 35 | 1.00 | ||||||
1–7 | 338 | 81 | 1.19 (0.91, 1.55) | 18 | 1.07 (0.64, 1.78) | 3 | 1.15 (0.33, 4.01) | 10 | 1.17 (0.61, 2.32) | 36 | 1.12 (0.77, 1.63) | 8 | 1.52 (0.70, 3.33) | ||||||
8–24 | 309 | 63 | 1.00 (0.74, 1.33) | 10 | 0.64 (0.33, 1.23) | 2 | 0.84 (0.19, 3.68) | 11 | 1.39 (0.78, 2.70) | 33 | 1.11 (0.75, 1.65) | 4 | 0.83 (0.29, 2.35) | ||||||
>24 | 310 | 64 | 1.02 (0.76, 1.36) | 19 | 1.30 (0.78, 2.12) | 1 | 0.45 (0.06, 3.41) | 12 | 1.63 (1.00, 3.10) | 26 | 0.84 (0.55, 1.28) | 1 | 0.23 (0.03, 1.70) | ||||||
ptrend | 0.98 | 0.92 | 0.48 | 0.12 | 0.67 | 0.21 |
Water factor level and years of exposure† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
TTHM§ (>20 μg/liter) | |||||||||||||||||||
Never | 1,435 | 333 | 1.00 | 71 | 1.00 | 10 | 1.00 | 33 | 1.00 | 174 | 1.00 | 25 | 1.00 | ||||||
1–11 | 548 | 115 | 0.94 (0.73, 1.19) | 26 | 0.94 (0.59, 1.50) | 5 | 1.26 (0.42, 3.77) | 16 | 1.13 (0.61, 2.09) | 50 | 0.82 (0.58, 1.14) | 10 | 1.04 (0.50, 2.20) | ||||||
12–31 | 680 | 145 | 0.93 (0.75, 1.16) | 36 | 1.06 (0.70, 1.61) | 6 | 1.23 (0.44, 3.44) | 22 | 1.32 (0.76, 2.30) | 63 | 0.80 (0.62, 1.10) | 11 | 0.89 (0.43, 1.84) | ||||||
>31 | 577 | 93 | 0.70 (0.55, 0.91) | 28 | 1.03 (0.66, 1.62) | 2 | 0.63 (0.14, 2.91) | 20 | 1.70 (1.00, 3.03) | 36 | 0.47 (0.32, 0.68) | 2 | 0.22 (0.05, 0.92) | ||||||
ptrend | 0.03 | 0.93 | 0.61 | 0.11 | 0.001 | 0.05 | |||||||||||||
TTHM (>40 μg/liter) | |||||||||||||||||||
Never | 1,793 | 392 | 1.00 | 84 | 1.00 | 13 | 1.00 | 40 | 1.00 | 200 | 1.00 | 30 | 1.00 | ||||||
1–11 | 503 | 104 | 0.97 (0.76, 1.24) | 26 | 1.10 (0.70, 1.73) | 4 | 1.07 (0.34, 3.34) | 16 | 1.32 (0.73, 2.41) | 43 | 0.81 (0.57, 1.15) | 8 | 0.96 (0.43, 2.08) | ||||||
12–31 | 492 | 113 | 1.06 (0.84, 1.35) | 26 | 1.11 (0.70, 1.74) | 4 | 1.04 (0.33, 3.24) | 20 | 1.70 (0.97, 3.03) | 46 | 0.87 (0.62, 1.23) | 10 | 1.17 (0.57, 2.43) | ||||||
>31 | 452 | 77 | 0.77 (0.59, 1.02) | 25 | 1.23 (0.78, 1.96) | 2 | 0.76 (0.17, 3.44) | 14 | 1.72 (1.01, 3.08) | 34 | 0.60 (0.41, 0.87) | 0 | 0.00 | ||||||
ptrend | 0.20 | 0.42 | 0.68 | 0.05 | 0.03 | 0.08 | |||||||||||||
BDCM§ (>5 μg/liter) | |||||||||||||||||||
Never | 2,283 | 478 | 1.00 | 114 | 1.00 | 17 | 1.00 | 58 | 1.00 | 228 | 1.00 | 35 | 1.00 | ||||||
1–7 | 338 | 81 | 1.19 (0.91, 1.55) | 18 | 1.07 (0.64, 1.78) | 3 | 1.15 (0.33, 4.01) | 10 | 1.17 (0.61, 2.32) | 36 | 1.12 (0.77, 1.63) | 8 | 1.52 (0.70, 3.33) | ||||||
8–24 | 309 | 63 | 1.00 (0.74, 1.33) | 10 | 0.64 (0.33, 1.23) | 2 | 0.84 (0.19, 3.68) | 11 | 1.39 (0.78, 2.70) | 33 | 1.11 (0.75, 1.65) | 4 | 0.83 (0.29, 2.35) | ||||||
>24 | 310 | 64 | 1.02 (0.76, 1.36) | 19 | 1.30 (0.78, 2.12) | 1 | 0.45 (0.06, 3.41) | 12 | 1.63 (1.00, 3.10) | 26 | 0.84 (0.55, 1.28) | 1 | 0.23 (0.03, 1.70) | ||||||
ptrend | 0.98 | 0.92 | 0.48 | 0.12 | 0.67 | 0.21 |
All odds ratios were adjusted for age, gender, and occupational exposure to benzene and ionizing radiation. Odds ratios were also adjusted for body mass index (all leukemia, AML, ALL, CML, CLL); passive smoking (all leukemia, AML, CLL); pack-years of smoking (AML, ALL, HCL); and education (all leukemia and CML).
Calculated over the 40 years before the interview for subjects with 30 or more years (75%) of known exposure information.
“All leukemia” included leukemia not otherwise specified as cases.
AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; CML, chronic myelocytic leukemia; CLL, chronic lymphocytic leukemia; HCL, hairy cell leukemia; OR, odds ratio; CI, confidence interval; TTHM, total trihalomethane; BDCM, bromodichloromethane.
Water factor level and years of exposure† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
TTHM§ (>20 μg/liter) | |||||||||||||||||||
Never | 1,435 | 333 | 1.00 | 71 | 1.00 | 10 | 1.00 | 33 | 1.00 | 174 | 1.00 | 25 | 1.00 | ||||||
1–11 | 548 | 115 | 0.94 (0.73, 1.19) | 26 | 0.94 (0.59, 1.50) | 5 | 1.26 (0.42, 3.77) | 16 | 1.13 (0.61, 2.09) | 50 | 0.82 (0.58, 1.14) | 10 | 1.04 (0.50, 2.20) | ||||||
12–31 | 680 | 145 | 0.93 (0.75, 1.16) | 36 | 1.06 (0.70, 1.61) | 6 | 1.23 (0.44, 3.44) | 22 | 1.32 (0.76, 2.30) | 63 | 0.80 (0.62, 1.10) | 11 | 0.89 (0.43, 1.84) | ||||||
>31 | 577 | 93 | 0.70 (0.55, 0.91) | 28 | 1.03 (0.66, 1.62) | 2 | 0.63 (0.14, 2.91) | 20 | 1.70 (1.00, 3.03) | 36 | 0.47 (0.32, 0.68) | 2 | 0.22 (0.05, 0.92) | ||||||
ptrend | 0.03 | 0.93 | 0.61 | 0.11 | 0.001 | 0.05 | |||||||||||||
TTHM (>40 μg/liter) | |||||||||||||||||||
Never | 1,793 | 392 | 1.00 | 84 | 1.00 | 13 | 1.00 | 40 | 1.00 | 200 | 1.00 | 30 | 1.00 | ||||||
1–11 | 503 | 104 | 0.97 (0.76, 1.24) | 26 | 1.10 (0.70, 1.73) | 4 | 1.07 (0.34, 3.34) | 16 | 1.32 (0.73, 2.41) | 43 | 0.81 (0.57, 1.15) | 8 | 0.96 (0.43, 2.08) | ||||||
12–31 | 492 | 113 | 1.06 (0.84, 1.35) | 26 | 1.11 (0.70, 1.74) | 4 | 1.04 (0.33, 3.24) | 20 | 1.70 (0.97, 3.03) | 46 | 0.87 (0.62, 1.23) | 10 | 1.17 (0.57, 2.43) | ||||||
>31 | 452 | 77 | 0.77 (0.59, 1.02) | 25 | 1.23 (0.78, 1.96) | 2 | 0.76 (0.17, 3.44) | 14 | 1.72 (1.01, 3.08) | 34 | 0.60 (0.41, 0.87) | 0 | 0.00 | ||||||
ptrend | 0.20 | 0.42 | 0.68 | 0.05 | 0.03 | 0.08 | |||||||||||||
BDCM§ (>5 μg/liter) | |||||||||||||||||||
Never | 2,283 | 478 | 1.00 | 114 | 1.00 | 17 | 1.00 | 58 | 1.00 | 228 | 1.00 | 35 | 1.00 | ||||||
1–7 | 338 | 81 | 1.19 (0.91, 1.55) | 18 | 1.07 (0.64, 1.78) | 3 | 1.15 (0.33, 4.01) | 10 | 1.17 (0.61, 2.32) | 36 | 1.12 (0.77, 1.63) | 8 | 1.52 (0.70, 3.33) | ||||||
8–24 | 309 | 63 | 1.00 (0.74, 1.33) | 10 | 0.64 (0.33, 1.23) | 2 | 0.84 (0.19, 3.68) | 11 | 1.39 (0.78, 2.70) | 33 | 1.11 (0.75, 1.65) | 4 | 0.83 (0.29, 2.35) | ||||||
>24 | 310 | 64 | 1.02 (0.76, 1.36) | 19 | 1.30 (0.78, 2.12) | 1 | 0.45 (0.06, 3.41) | 12 | 1.63 (1.00, 3.10) | 26 | 0.84 (0.55, 1.28) | 1 | 0.23 (0.03, 1.70) | ||||||
ptrend | 0.98 | 0.92 | 0.48 | 0.12 | 0.67 | 0.21 |
Water factor level and years of exposure† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
TTHM§ (>20 μg/liter) | |||||||||||||||||||
Never | 1,435 | 333 | 1.00 | 71 | 1.00 | 10 | 1.00 | 33 | 1.00 | 174 | 1.00 | 25 | 1.00 | ||||||
1–11 | 548 | 115 | 0.94 (0.73, 1.19) | 26 | 0.94 (0.59, 1.50) | 5 | 1.26 (0.42, 3.77) | 16 | 1.13 (0.61, 2.09) | 50 | 0.82 (0.58, 1.14) | 10 | 1.04 (0.50, 2.20) | ||||||
12–31 | 680 | 145 | 0.93 (0.75, 1.16) | 36 | 1.06 (0.70, 1.61) | 6 | 1.23 (0.44, 3.44) | 22 | 1.32 (0.76, 2.30) | 63 | 0.80 (0.62, 1.10) | 11 | 0.89 (0.43, 1.84) | ||||||
>31 | 577 | 93 | 0.70 (0.55, 0.91) | 28 | 1.03 (0.66, 1.62) | 2 | 0.63 (0.14, 2.91) | 20 | 1.70 (1.00, 3.03) | 36 | 0.47 (0.32, 0.68) | 2 | 0.22 (0.05, 0.92) | ||||||
ptrend | 0.03 | 0.93 | 0.61 | 0.11 | 0.001 | 0.05 | |||||||||||||
TTHM (>40 μg/liter) | |||||||||||||||||||
Never | 1,793 | 392 | 1.00 | 84 | 1.00 | 13 | 1.00 | 40 | 1.00 | 200 | 1.00 | 30 | 1.00 | ||||||
1–11 | 503 | 104 | 0.97 (0.76, 1.24) | 26 | 1.10 (0.70, 1.73) | 4 | 1.07 (0.34, 3.34) | 16 | 1.32 (0.73, 2.41) | 43 | 0.81 (0.57, 1.15) | 8 | 0.96 (0.43, 2.08) | ||||||
12–31 | 492 | 113 | 1.06 (0.84, 1.35) | 26 | 1.11 (0.70, 1.74) | 4 | 1.04 (0.33, 3.24) | 20 | 1.70 (0.97, 3.03) | 46 | 0.87 (0.62, 1.23) | 10 | 1.17 (0.57, 2.43) | ||||||
>31 | 452 | 77 | 0.77 (0.59, 1.02) | 25 | 1.23 (0.78, 1.96) | 2 | 0.76 (0.17, 3.44) | 14 | 1.72 (1.01, 3.08) | 34 | 0.60 (0.41, 0.87) | 0 | 0.00 | ||||||
ptrend | 0.20 | 0.42 | 0.68 | 0.05 | 0.03 | 0.08 | |||||||||||||
BDCM§ (>5 μg/liter) | |||||||||||||||||||
Never | 2,283 | 478 | 1.00 | 114 | 1.00 | 17 | 1.00 | 58 | 1.00 | 228 | 1.00 | 35 | 1.00 | ||||||
1–7 | 338 | 81 | 1.19 (0.91, 1.55) | 18 | 1.07 (0.64, 1.78) | 3 | 1.15 (0.33, 4.01) | 10 | 1.17 (0.61, 2.32) | 36 | 1.12 (0.77, 1.63) | 8 | 1.52 (0.70, 3.33) | ||||||
8–24 | 309 | 63 | 1.00 (0.74, 1.33) | 10 | 0.64 (0.33, 1.23) | 2 | 0.84 (0.19, 3.68) | 11 | 1.39 (0.78, 2.70) | 33 | 1.11 (0.75, 1.65) | 4 | 0.83 (0.29, 2.35) | ||||||
>24 | 310 | 64 | 1.02 (0.76, 1.36) | 19 | 1.30 (0.78, 2.12) | 1 | 0.45 (0.06, 3.41) | 12 | 1.63 (1.00, 3.10) | 26 | 0.84 (0.55, 1.28) | 1 | 0.23 (0.03, 1.70) | ||||||
ptrend | 0.98 | 0.92 | 0.48 | 0.12 | 0.67 | 0.21 |
All odds ratios were adjusted for age, gender, and occupational exposure to benzene and ionizing radiation. Odds ratios were also adjusted for body mass index (all leukemia, AML, ALL, CML, CLL); passive smoking (all leukemia, AML, CLL); pack-years of smoking (AML, ALL, HCL); and education (all leukemia and CML).
Calculated over the 40 years before the interview for subjects with 30 or more years (75%) of known exposure information.
“All leukemia” included leukemia not otherwise specified as cases.
AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; CML, chronic myelocytic leukemia; CLL, chronic lymphocytic leukemia; HCL, hairy cell leukemia; OR, odds ratio; CI, confidence interval; TTHM, total trihalomethane; BDCM, bromodichloromethane.
In contrast to these findings, we found that the risks of all leukemias combined, chronic lymphocytic leukemia, and hairy cell leukemia decreased with increasing years of exposure to total trihalomethanes and bromodichloromethane. The adjusted odds ratio associated with the highest exposure duration to total trihalomethanes of more than 40 μg/liter was 0.60 (95 percent CI: 0.41, 0.87) for chronic lymphocytic leukemia. Similar results were also obtained for all leukemias combined, chronic lymphocytic leukemia, and hairy cell leukemia with increasing duration of exposure to total trihalomethanes of more than 20 μg/liter and to bromodichloromethane of more than 5 μg/liter.
The analyses presented in table 4 were restricted to those subjects who were exposed only to chlorinated water supplies during the 40-year period studied in an attempt to examine the effect of exposure to different estimated trihalomethane levels. Among these subjects (419 cases and 2,106 controls), we examined the risk of adult leukemia by estimated levels of total trihalomethanes (≤20, >20–40, and >40 μg/liter) and bromodichloromethane (≤5, >5–10, and >10 μg/liter). The odds ratios were higher with the higher concentration of bromodichloromethane for chronic myelocytic leukemia and acute lymphocytic leukemia, and the increased concentration of total trihalomethanes was associated with a significant increased risk for chronic myelocytic leukemia. Compared with those subjects exposed to a total trihalomethane level of less than or equal to 20 μg/liter, those exposed to a level of more than 40 μg/liter were found to have an adjusted odds ratio of 1.76 (95 percent CI: 1.01, 3.10).
Water factor concentration† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
TTHM§ concentration (μg/liter) | |||||||||||||||||||
≤20 | 1,044 | 227 | 1.00 | 47 | 1.00 | 7 | 1.00 | 22 | 1.00 | 117 | 1.00 | 20 | 1.00 | ||||||
>20–40 | 224 | 37 | 0.80 (0.55, 1.17) | 9 | 0.90 (0.42, 1.80) | 2 | 1.45 (0.30, 7.26) | 4 | 0.90 (0.32, 2.58) | 15 | 0.63 (0.36, 1.10) | 3 | 0.85 (0.23, 3.16) | ||||||
>40 | 838 | 155 | 0.90 (0.70, 1.10) | 40 | 1.03 (0.68, 1.60) | 7 | 1.42 (0.50, 4.10) | 30 | 1.76 (1.01, 3.10) | 67 | 0.73 (0.51, 0.97) | 4 | 0.31 (0.10, 0.80) | ||||||
ptrend | 0.14 | 0.80 | 0.86 | 0.04 | 0.03 | 0.02 | |||||||||||||
BDCM§ concentration (μg/liter) | |||||||||||||||||||
≤5 | 1,729 | 345 | 1.00 | 80 | 1.00 | 11 | 1.00 | 43 | 1.00 | 168 | 1.00 | 22 | 1.00 | ||||||
>5–10 | 326 | 66 | 1.06 (0.79, 1.42) | 15 | 1.02 (0.58, 1.79) | 4 | 2.00 (0.63, 6.48) | 10 | 1.30 (0.63, 2.58) | 29 | 0.92 (0.60, 1.40) | 4 | 1.10 (0.37, 3.21) | ||||||
>10 | 51 | 8 | 0.80 (0.37, 1.68) | 1 | 0.47 (0.10, 3.41) | 1 | 3.76 (0.48, 31.9) | 3 | 2.60 (0.80, 8.71) | 2 | 0.41 (0.10, 1.69) | 1 | 1.43 (0.24, 12.3) | ||||||
ptrend | 0.75 | 0.58 | 0.18 | 0.19 | 0.27 | 0.83 |
Water factor concentration† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
TTHM§ concentration (μg/liter) | |||||||||||||||||||
≤20 | 1,044 | 227 | 1.00 | 47 | 1.00 | 7 | 1.00 | 22 | 1.00 | 117 | 1.00 | 20 | 1.00 | ||||||
>20–40 | 224 | 37 | 0.80 (0.55, 1.17) | 9 | 0.90 (0.42, 1.80) | 2 | 1.45 (0.30, 7.26) | 4 | 0.90 (0.32, 2.58) | 15 | 0.63 (0.36, 1.10) | 3 | 0.85 (0.23, 3.16) | ||||||
>40 | 838 | 155 | 0.90 (0.70, 1.10) | 40 | 1.03 (0.68, 1.60) | 7 | 1.42 (0.50, 4.10) | 30 | 1.76 (1.01, 3.10) | 67 | 0.73 (0.51, 0.97) | 4 | 0.31 (0.10, 0.80) | ||||||
ptrend | 0.14 | 0.80 | 0.86 | 0.04 | 0.03 | 0.02 | |||||||||||||
BDCM§ concentration (μg/liter) | |||||||||||||||||||
≤5 | 1,729 | 345 | 1.00 | 80 | 1.00 | 11 | 1.00 | 43 | 1.00 | 168 | 1.00 | 22 | 1.00 | ||||||
>5–10 | 326 | 66 | 1.06 (0.79, 1.42) | 15 | 1.02 (0.58, 1.79) | 4 | 2.00 (0.63, 6.48) | 10 | 1.30 (0.63, 2.58) | 29 | 0.92 (0.60, 1.40) | 4 | 1.10 (0.37, 3.21) | ||||||
>10 | 51 | 8 | 0.80 (0.37, 1.68) | 1 | 0.47 (0.10, 3.41) | 1 | 3.76 (0.48, 31.9) | 3 | 2.60 (0.80, 8.71) | 2 | 0.41 (0.10, 1.69) | 1 | 1.43 (0.24, 12.3) | ||||||
ptrend | 0.75 | 0.58 | 0.18 | 0.19 | 0.27 | 0.83 |
All odds ratios were adjusted for age, gender, occupational exposure to benzene and ionizing radiation, and daily tap water consumption. Odds ratios were also adjusted for body mass index (all leukemia, AML, ALL, CML, CLL); passive smoking (all leukemia, AML, CLL); pack-years of smoking (AML, ALL, HCL); and education (all leukemia and CML).
Calculated over the 40 years before the interview for subjects with 30 or more years (75%) of known exposure information.
“All leukemia” included leukemia not otherwise specified as cases.
AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; CML, chronic myelocytic leukemia; CLL, chronic lymphocytic leukemia; HCL, hairy cell leukemia; OR, odds ratio; CI, confidence interval; TTHM, total trihalomethane; BDCM, bromodichloromethane.
Water factor concentration† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
TTHM§ concentration (μg/liter) | |||||||||||||||||||
≤20 | 1,044 | 227 | 1.00 | 47 | 1.00 | 7 | 1.00 | 22 | 1.00 | 117 | 1.00 | 20 | 1.00 | ||||||
>20–40 | 224 | 37 | 0.80 (0.55, 1.17) | 9 | 0.90 (0.42, 1.80) | 2 | 1.45 (0.30, 7.26) | 4 | 0.90 (0.32, 2.58) | 15 | 0.63 (0.36, 1.10) | 3 | 0.85 (0.23, 3.16) | ||||||
>40 | 838 | 155 | 0.90 (0.70, 1.10) | 40 | 1.03 (0.68, 1.60) | 7 | 1.42 (0.50, 4.10) | 30 | 1.76 (1.01, 3.10) | 67 | 0.73 (0.51, 0.97) | 4 | 0.31 (0.10, 0.80) | ||||||
ptrend | 0.14 | 0.80 | 0.86 | 0.04 | 0.03 | 0.02 | |||||||||||||
BDCM§ concentration (μg/liter) | |||||||||||||||||||
≤5 | 1,729 | 345 | 1.00 | 80 | 1.00 | 11 | 1.00 | 43 | 1.00 | 168 | 1.00 | 22 | 1.00 | ||||||
>5–10 | 326 | 66 | 1.06 (0.79, 1.42) | 15 | 1.02 (0.58, 1.79) | 4 | 2.00 (0.63, 6.48) | 10 | 1.30 (0.63, 2.58) | 29 | 0.92 (0.60, 1.40) | 4 | 1.10 (0.37, 3.21) | ||||||
>10 | 51 | 8 | 0.80 (0.37, 1.68) | 1 | 0.47 (0.10, 3.41) | 1 | 3.76 (0.48, 31.9) | 3 | 2.60 (0.80, 8.71) | 2 | 0.41 (0.10, 1.69) | 1 | 1.43 (0.24, 12.3) | ||||||
ptrend | 0.75 | 0.58 | 0.18 | 0.19 | 0.27 | 0.83 |
Water factor concentration† . | Controls (no.) . | All leukemia‡ . | . | AML§ . | . | ALL§ . | . | CML§ . | . | CLL§ . | . | HCL§ . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR§ (95% CI§) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
TTHM§ concentration (μg/liter) | |||||||||||||||||||
≤20 | 1,044 | 227 | 1.00 | 47 | 1.00 | 7 | 1.00 | 22 | 1.00 | 117 | 1.00 | 20 | 1.00 | ||||||
>20–40 | 224 | 37 | 0.80 (0.55, 1.17) | 9 | 0.90 (0.42, 1.80) | 2 | 1.45 (0.30, 7.26) | 4 | 0.90 (0.32, 2.58) | 15 | 0.63 (0.36, 1.10) | 3 | 0.85 (0.23, 3.16) | ||||||
>40 | 838 | 155 | 0.90 (0.70, 1.10) | 40 | 1.03 (0.68, 1.60) | 7 | 1.42 (0.50, 4.10) | 30 | 1.76 (1.01, 3.10) | 67 | 0.73 (0.51, 0.97) | 4 | 0.31 (0.10, 0.80) | ||||||
ptrend | 0.14 | 0.80 | 0.86 | 0.04 | 0.03 | 0.02 | |||||||||||||
BDCM§ concentration (μg/liter) | |||||||||||||||||||
≤5 | 1,729 | 345 | 1.00 | 80 | 1.00 | 11 | 1.00 | 43 | 1.00 | 168 | 1.00 | 22 | 1.00 | ||||||
>5–10 | 326 | 66 | 1.06 (0.79, 1.42) | 15 | 1.02 (0.58, 1.79) | 4 | 2.00 (0.63, 6.48) | 10 | 1.30 (0.63, 2.58) | 29 | 0.92 (0.60, 1.40) | 4 | 1.10 (0.37, 3.21) | ||||||
>10 | 51 | 8 | 0.80 (0.37, 1.68) | 1 | 0.47 (0.10, 3.41) | 1 | 3.76 (0.48, 31.9) | 3 | 2.60 (0.80, 8.71) | 2 | 0.41 (0.10, 1.69) | 1 | 1.43 (0.24, 12.3) | ||||||
ptrend | 0.75 | 0.58 | 0.18 | 0.19 | 0.27 | 0.83 |
All odds ratios were adjusted for age, gender, occupational exposure to benzene and ionizing radiation, and daily tap water consumption. Odds ratios were also adjusted for body mass index (all leukemia, AML, ALL, CML, CLL); passive smoking (all leukemia, AML, CLL); pack-years of smoking (AML, ALL, HCL); and education (all leukemia and CML).
Calculated over the 40 years before the interview for subjects with 30 or more years (75%) of known exposure information.
“All leukemia” included leukemia not otherwise specified as cases.
AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; CML, chronic myelocytic leukemia; CLL, chronic lymphocytic leukemia; HCL, hairy cell leukemia; OR, odds ratio; CI, confidence interval; TTHM, total trihalomethane; BDCM, bromodichloromethane.
Among the subjects exposed to chlorinated water sources only, we found the average daily intake of tap water to be similar among all studied leukemia cases, as well as its subtypes, and controls (data not shown). However, when we evaluated the effect of quantity of water ingested on the risk of leukemia stratified by the different total trihalomethane levels, we observed a statistically significant risk estimate representing a doubling of risk for chronic myelocytic leukemia among those subjects who consumed more than 1.5 liters of chlorinated water with estimated total trihalomethanes of more than 40 μg/liter (odds ratio = 2.03, 95 percent CI: 1.02, 5.76). For all leukemias combined and other leukemia subtypes, there was no clear evidence of associations, and patterns of estimated risks were inconsistent (table 5). For the effect of quantity of ingested water on adult leukemia risk stratified by level of bromodichloromethane, we did not have enough cases in the studied strata to estimate such an effect.
TTHM† levels and tap water consumption (liters/day) . | Controls (no.) . | All leukemia combined‡ . | . | AML† . | . | ALL† . | . | CML† . | . | CLL† . | . | HCL† . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR† (95% CI†) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
≤20 μg/liter | |||||||||||||||||||
<1 | 365 | 71 | 1.00 | 15 | 1.00 | 2 | 1.00 | 8 | 1.00 | 34 | 1.00 | 6 | 1.00 | ||||||
1–1.5 | 377 | 79 | 1.08 (0.76, 1.54) | 21 | 1.38 (0.70, 2.73) | 4 | 2.10 (0.37, 11.83) | 6 | 0.73 (0.25, 2.10) | 40 | 1.14 (0.71, 1.86) | 5 | 0.85 (0.25, 2.82) | ||||||
>1.5 | 302 | 77 | 1.28 (0.89, 1.83) | 11 | 0.90 (0.40, 1.96) | 2 | 1.41 (0.20, 10.37) | 8 | 1.20 (0.41, 3.05) | 43 | 1.43 (0.82, 2.44) | 9 | 1.92 (0.67, 5.53) | ||||||
ptrend | 0.13 | 0.83 | 0.83 | 0.72 | 0.07 | 0.24 | |||||||||||||
>20–40 μg/liter | |||||||||||||||||||
<1 | 78 | 17 | 1.00 | 7 | 1.00 | 0 | 1.00 | 1 | 1.00 | 5 | 1.00 | 1 | 1.00 | ||||||
1–1.5 | 71 | 12 | 0.75 (0.35, 1.68) | 1 | 0.50 (0.07, 2.52) | 1 | 1 | 1.10 (0.12, 8.40) | 7 | 1.30 (0.40, 4.35) | 1 | 1.10 (0.06, 17.2) | |||||||
>1.5 | 75 | 8 | 0.55 (0.20, 1.26) | 1 | 0.85 (0.15, 3.42) | 1 | 2 | 1.98 (0.96, 5.14) | 3 | 0.78 (0.15, 2.64) | 1 | 1.40 (0.10, 22.2) | |||||||
ptrend | 0.11 | 0.45 | 0.38 | 0.52 | 0.58 | 0.97 | |||||||||||||
>40 μg/liter | |||||||||||||||||||
<1 | 283 | 53 | 1.00 | 15 | 1.00 | 2 | 1.00 | 9 | 1.00 | 24 | 1.00 | 2 | 1.00 | ||||||
1–1.5 | 310 | 46 | 0.90 (0.55, 1.35) | 12 | 0.85 (0.35, 1.60) | 3 | 1.82 (0.30, 10.9) | 6 | 1.16 (0.58, 3.46) | 21 | 0.85 (0.44, 1.44) | 1 | 0.55 (0.05, 5.45) | ||||||
>1.5 | 245 | 56 | 1.25 (0.83, 1.87) | 13 | 1.05 (0.50, 2.23) | 2 | 1.36 (0.20, 9.56) | 15 | 2.03 (1.02, 5.76) | 22 | 1.05 (0.60, 1.89) | 1 | 0.75 (0.07, 8.14) | ||||||
ptrend | 0.35 | 0.97 | 0.88 | 0.10 | 0.87 | 0.60 |
TTHM† levels and tap water consumption (liters/day) . | Controls (no.) . | All leukemia combined‡ . | . | AML† . | . | ALL† . | . | CML† . | . | CLL† . | . | HCL† . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR† (95% CI†) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
≤20 μg/liter | |||||||||||||||||||
<1 | 365 | 71 | 1.00 | 15 | 1.00 | 2 | 1.00 | 8 | 1.00 | 34 | 1.00 | 6 | 1.00 | ||||||
1–1.5 | 377 | 79 | 1.08 (0.76, 1.54) | 21 | 1.38 (0.70, 2.73) | 4 | 2.10 (0.37, 11.83) | 6 | 0.73 (0.25, 2.10) | 40 | 1.14 (0.71, 1.86) | 5 | 0.85 (0.25, 2.82) | ||||||
>1.5 | 302 | 77 | 1.28 (0.89, 1.83) | 11 | 0.90 (0.40, 1.96) | 2 | 1.41 (0.20, 10.37) | 8 | 1.20 (0.41, 3.05) | 43 | 1.43 (0.82, 2.44) | 9 | 1.92 (0.67, 5.53) | ||||||
ptrend | 0.13 | 0.83 | 0.83 | 0.72 | 0.07 | 0.24 | |||||||||||||
>20–40 μg/liter | |||||||||||||||||||
<1 | 78 | 17 | 1.00 | 7 | 1.00 | 0 | 1.00 | 1 | 1.00 | 5 | 1.00 | 1 | 1.00 | ||||||
1–1.5 | 71 | 12 | 0.75 (0.35, 1.68) | 1 | 0.50 (0.07, 2.52) | 1 | 1 | 1.10 (0.12, 8.40) | 7 | 1.30 (0.40, 4.35) | 1 | 1.10 (0.06, 17.2) | |||||||
>1.5 | 75 | 8 | 0.55 (0.20, 1.26) | 1 | 0.85 (0.15, 3.42) | 1 | 2 | 1.98 (0.96, 5.14) | 3 | 0.78 (0.15, 2.64) | 1 | 1.40 (0.10, 22.2) | |||||||
ptrend | 0.11 | 0.45 | 0.38 | 0.52 | 0.58 | 0.97 | |||||||||||||
>40 μg/liter | |||||||||||||||||||
<1 | 283 | 53 | 1.00 | 15 | 1.00 | 2 | 1.00 | 9 | 1.00 | 24 | 1.00 | 2 | 1.00 | ||||||
1–1.5 | 310 | 46 | 0.90 (0.55, 1.35) | 12 | 0.85 (0.35, 1.60) | 3 | 1.82 (0.30, 10.9) | 6 | 1.16 (0.58, 3.46) | 21 | 0.85 (0.44, 1.44) | 1 | 0.55 (0.05, 5.45) | ||||||
>1.5 | 245 | 56 | 1.25 (0.83, 1.87) | 13 | 1.05 (0.50, 2.23) | 2 | 1.36 (0.20, 9.56) | 15 | 2.03 (1.02, 5.76) | 22 | 1.05 (0.60, 1.89) | 1 | 0.75 (0.07, 8.14) | ||||||
ptrend | 0.35 | 0.97 | 0.88 | 0.10 | 0.87 | 0.60 |
All odds ratios were adjusted for age, gender, and occupational exposure to benzene and ionizing radiation. Odds ratios were also adjusted for body mass index (all leukemia, AML, ALL, CML, CLL); passive smoking (all leukemia, AML, CLL); pack-years of smoking (AML, ALL, HCL); and education (all leukemia and CML).
TTHM, total trihalomethane; AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; CML, chronic myelocytic leukemia; CLL, chronic lymphocytic leukemia; HCL, hairy cell leukemia; OR, odds ratio; CI, confidence interval.
“All leukemia” included leukemia not otherwise specified as cases.
TTHM† levels and tap water consumption (liters/day) . | Controls (no.) . | All leukemia combined‡ . | . | AML† . | . | ALL† . | . | CML† . | . | CLL† . | . | HCL† . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR† (95% CI†) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
≤20 μg/liter | |||||||||||||||||||
<1 | 365 | 71 | 1.00 | 15 | 1.00 | 2 | 1.00 | 8 | 1.00 | 34 | 1.00 | 6 | 1.00 | ||||||
1–1.5 | 377 | 79 | 1.08 (0.76, 1.54) | 21 | 1.38 (0.70, 2.73) | 4 | 2.10 (0.37, 11.83) | 6 | 0.73 (0.25, 2.10) | 40 | 1.14 (0.71, 1.86) | 5 | 0.85 (0.25, 2.82) | ||||||
>1.5 | 302 | 77 | 1.28 (0.89, 1.83) | 11 | 0.90 (0.40, 1.96) | 2 | 1.41 (0.20, 10.37) | 8 | 1.20 (0.41, 3.05) | 43 | 1.43 (0.82, 2.44) | 9 | 1.92 (0.67, 5.53) | ||||||
ptrend | 0.13 | 0.83 | 0.83 | 0.72 | 0.07 | 0.24 | |||||||||||||
>20–40 μg/liter | |||||||||||||||||||
<1 | 78 | 17 | 1.00 | 7 | 1.00 | 0 | 1.00 | 1 | 1.00 | 5 | 1.00 | 1 | 1.00 | ||||||
1–1.5 | 71 | 12 | 0.75 (0.35, 1.68) | 1 | 0.50 (0.07, 2.52) | 1 | 1 | 1.10 (0.12, 8.40) | 7 | 1.30 (0.40, 4.35) | 1 | 1.10 (0.06, 17.2) | |||||||
>1.5 | 75 | 8 | 0.55 (0.20, 1.26) | 1 | 0.85 (0.15, 3.42) | 1 | 2 | 1.98 (0.96, 5.14) | 3 | 0.78 (0.15, 2.64) | 1 | 1.40 (0.10, 22.2) | |||||||
ptrend | 0.11 | 0.45 | 0.38 | 0.52 | 0.58 | 0.97 | |||||||||||||
>40 μg/liter | |||||||||||||||||||
<1 | 283 | 53 | 1.00 | 15 | 1.00 | 2 | 1.00 | 9 | 1.00 | 24 | 1.00 | 2 | 1.00 | ||||||
1–1.5 | 310 | 46 | 0.90 (0.55, 1.35) | 12 | 0.85 (0.35, 1.60) | 3 | 1.82 (0.30, 10.9) | 6 | 1.16 (0.58, 3.46) | 21 | 0.85 (0.44, 1.44) | 1 | 0.55 (0.05, 5.45) | ||||||
>1.5 | 245 | 56 | 1.25 (0.83, 1.87) | 13 | 1.05 (0.50, 2.23) | 2 | 1.36 (0.20, 9.56) | 15 | 2.03 (1.02, 5.76) | 22 | 1.05 (0.60, 1.89) | 1 | 0.75 (0.07, 8.14) | ||||||
ptrend | 0.35 | 0.97 | 0.88 | 0.10 | 0.87 | 0.60 |
TTHM† levels and tap water consumption (liters/day) . | Controls (no.) . | All leukemia combined‡ . | . | AML† . | . | ALL† . | . | CML† . | . | CLL† . | . | HCL† . | . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
. | . | Cases (no.) . | OR† (95% CI†) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | Cases (no.) . | OR (95% CI) . | ||||||
≤20 μg/liter | |||||||||||||||||||
<1 | 365 | 71 | 1.00 | 15 | 1.00 | 2 | 1.00 | 8 | 1.00 | 34 | 1.00 | 6 | 1.00 | ||||||
1–1.5 | 377 | 79 | 1.08 (0.76, 1.54) | 21 | 1.38 (0.70, 2.73) | 4 | 2.10 (0.37, 11.83) | 6 | 0.73 (0.25, 2.10) | 40 | 1.14 (0.71, 1.86) | 5 | 0.85 (0.25, 2.82) | ||||||
>1.5 | 302 | 77 | 1.28 (0.89, 1.83) | 11 | 0.90 (0.40, 1.96) | 2 | 1.41 (0.20, 10.37) | 8 | 1.20 (0.41, 3.05) | 43 | 1.43 (0.82, 2.44) | 9 | 1.92 (0.67, 5.53) | ||||||
ptrend | 0.13 | 0.83 | 0.83 | 0.72 | 0.07 | 0.24 | |||||||||||||
>20–40 μg/liter | |||||||||||||||||||
<1 | 78 | 17 | 1.00 | 7 | 1.00 | 0 | 1.00 | 1 | 1.00 | 5 | 1.00 | 1 | 1.00 | ||||||
1–1.5 | 71 | 12 | 0.75 (0.35, 1.68) | 1 | 0.50 (0.07, 2.52) | 1 | 1 | 1.10 (0.12, 8.40) | 7 | 1.30 (0.40, 4.35) | 1 | 1.10 (0.06, 17.2) | |||||||
>1.5 | 75 | 8 | 0.55 (0.20, 1.26) | 1 | 0.85 (0.15, 3.42) | 1 | 2 | 1.98 (0.96, 5.14) | 3 | 0.78 (0.15, 2.64) | 1 | 1.40 (0.10, 22.2) | |||||||
ptrend | 0.11 | 0.45 | 0.38 | 0.52 | 0.58 | 0.97 | |||||||||||||
>40 μg/liter | |||||||||||||||||||
<1 | 283 | 53 | 1.00 | 15 | 1.00 | 2 | 1.00 | 9 | 1.00 | 24 | 1.00 | 2 | 1.00 | ||||||
1–1.5 | 310 | 46 | 0.90 (0.55, 1.35) | 12 | 0.85 (0.35, 1.60) | 3 | 1.82 (0.30, 10.9) | 6 | 1.16 (0.58, 3.46) | 21 | 0.85 (0.44, 1.44) | 1 | 0.55 (0.05, 5.45) | ||||||
>1.5 | 245 | 56 | 1.25 (0.83, 1.87) | 13 | 1.05 (0.50, 2.23) | 2 | 1.36 (0.20, 9.56) | 15 | 2.03 (1.02, 5.76) | 22 | 1.05 (0.60, 1.89) | 1 | 0.75 (0.07, 8.14) | ||||||
ptrend | 0.35 | 0.97 | 0.88 | 0.10 | 0.87 | 0.60 |
All odds ratios were adjusted for age, gender, and occupational exposure to benzene and ionizing radiation. Odds ratios were also adjusted for body mass index (all leukemia, AML, ALL, CML, CLL); passive smoking (all leukemia, AML, CLL); pack-years of smoking (AML, ALL, HCL); and education (all leukemia and CML).
TTHM, total trihalomethane; AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; CML, chronic myelocytic leukemia; CLL, chronic lymphocytic leukemia; HCL, hairy cell leukemia; OR, odds ratio; CI, confidence interval.
“All leukemia” included leukemia not otherwise specified as cases.
DISCUSSION
We found some variation between adult leukemia risk and chronic exposure to disinfection chlorination by-products. For chronic myelocytic leukemia, there were positive associations with nearly all of the studied chlorination disinfection by-product variables. Duration of exposure seems to be an important component of chronic myelocytic leukemia risk. In contrast, the odds ratios for other studied leukemia subtypes were found to decrease by increasing years of exposure to the studied chlorination disinfection by-product variables, with a significant protective effect notable for chronic lymphocytic leukemia and hairy cell leukemia.
We are aware of only two studies that we can compare these results with, and both were ecologic in nature. Trihalomethanes were not associated with the risk of adult leukemia in the first small study conducted in New Jersey (13). However, in the second study conducted in the southwest of England, a statistically significant positive relation was observed for the highest trihalomethane levels and adult leukemia risk (14). Consistent with our study results, the highest rate ratio reported in this positive study was for chronic myelocytic leukemia. However, it is difficult to compare our study results directly with those of ecologic studies because of differences in the study design and nature of data used.
The genotoxic and carcinogenic potential of chlorination disinfection by-products has been demonstrated in toxicologic studies (29, 30), providing some biologic rationale for elevated cancer risk. In experimental studies, bromodichloromethane has been found to induce chromosomal aberrations in mouse bone marrow cells in vivo (31) and to enhance the induction of sister chromatid exchanges in human bone marrow cells in vitro (32). Approximately 90 percent of patients with chronic myelocytic leukemia are associated with chromosomal abnormalities with a characteristic abnormal Philadelphia (Ph) chromosome (33). Such chromosomal abnormalities are less common in other leukemia subtypes and, if they occur, the prognosis is very bad (34). In our study, the higher risk estimates for chronic myelocytic leukemia were associated with bromodichloromethane.
Our study has a number of strengths that include being population based and having accurate identification of leukemia cases by the provincial cancer registries. Considering the rarity of leukemias and cancers in general, this study had a relatively large number of cases, thus allowing an extensive examination of the association by leukemia subtypes. The availability of information in the NECSS database has allowed us to measure and control for a wide range of potential confounders, thereby overcoming some of the limitations in the previous ecologic studies. Restricting our study analyses to subjects with at least 30 years of exposure information over the studied 40-year period has greatly reduced the risk of exposure misclassification.
Consideration must also be given to the potential limitations in the present study that may have influenced the associations observed. The primary concern in this study is that a low proportion of potentially eligible cases were included in the analysis. Of 1,997 adult leukemia cases identified, only 1,068 (53.5 percent) are represented. Case subjects were lost because of death (292 cases), refusal of physicians to give consent because of cases' ill health (160 cases), and refusal of the cases to participate (467 cases). The possibility of selection bias should be considered if nonrespondents differed from those analyzed in terms of the studied risk factors. The finding that the majority of acute lymphocytic leukemia cases were nonsmokers (61 percent), suggesting that nonsmokers are at much higher risk for acute lymphocytic leukemia than are smokers, may be a signal of response bias. Acute lymphocytic leukemia is very rare in the adult population and is not known to be associated with smoking in many other studies. Because we did not include deceased and severely ill cases, it is probable that acute cases are less well presented in this study compared with chronic cases, which are often in better health. In such a case, possible selection bias should be less important for chronic myelocytic leukemia and chronic lymphocytic leukemia.
Comparison of excluded cases and controls with those left in the analysis demonstrates that the excluded population was somewhat younger, better educated, more urban, more occupationally exposed to benzene, more likely to be current smokers, less likely to be obese, and less exposed to passive smoking, but there was no differential in these characteristics between total cases and controls. Although there were some minor differences for some of these variables between the excluded and included subtype cases, all these variables were considered in our analyses. Comparison of educational level between the analyzed controls and 1996 census data of the eight participating provinces, stratified by age and sex (data not shown), also showed that our controls were less educated than the population census. Most of this selection seems due to the criteria we used for inclusion in the data analysis (30 years of water history during the 40 years before the interview). It is difficult to evaluate the impact of this potential bias on our results. Since this selection bias was in the same direction for cases and controls and since education was taken into account in our analysis as a potential confounder, it probably had a minor impact on our results. In addition, while we ignored the family income variable in further analysis because of its frequent missing values, restricted analysis for those subjects with family income data available did not show any difference from the results presented, particularly for chronic myelocytic leukemia (data not shown).
Another limitation of our study is the inability to distinguish between the impacts of different exposure routes of chlorination disinfection by-products. Exposure may occur through several different routes, including dermal exposure and inhalation (35). As we did not have information on individual patterns of showering or bathing, the assigned category of exposure may not accurately reflect the actual trihalomethane uptake. Furthermore, only trihalomethane exposures at home were taken into account in this study and not those outside the home, for example, at work, where the concentrations might be different, and this may lead to exposure misclassification. Water consumption outside the home can be considerable (35). It is likely that women spent more time at home over the 40-year period studied than did men, and this may affect the results by gender. However, stratified analysis by gender showed no significant risk difference between men and women, particularly for chronic myelocytic leukemia.
In conclusion, it does seem possible that the risk of adult leukemia varies according to exposure to different types of chlorination disinfection by-products. Total trihalomethanes and bromodichloromethane may be particularly important in the etiology of chronic myelocytic leukemia, but the possible protective effect of chlorination disinfection by-products on chronic lymphocytic leukemia remains unclear. Random error or selection bias could explain these results. Other studies are needed to confirm our findings.
Original funding for the NECSS was provided through the Canadian government's Action Plan on Health and the Environment.
The authors thank Dr. Y. Mao of the Public Health Agency of Canada, Dr. James Argo (environmental consultant), and Dr. J. Siemiatycki and Dr. Marie-Élise Parent of the Institut National de Recherche et de Sécurité–Institute Armand-Frappier. They also thank Dr. W. King of the Department of Community Health and Epidemiology, Queen's University, and Suzanne Gingras from the Unité de Recherche en Santé Publique of the Centre Hospitalier Universitaire de Québec.
The Canadian Cancer Registries Epidemiology Research Group comprises a Principal Investigator from each of the provincial cancer registries involved in the National Enhanced Cancer Surveillance System: Bertha Paulse, Newfoundland Cancer Foundation; Ron Dewar, Nova Scotia Cancer Registry; Dr. Dagny Dryer, Prince Edward Island Cancer Registry; Dr. Nancy Kreiger, Cancer Care Ontario; Dr. Erich Kliewer, Cancer Care Manitoba; Diane Robson, Saskatchewan Cancer Foundation; Dr. Shirley Fincham, Division of Epidemiology, Prevention, and Screening, Alberta Cancer Board; and Dr. Nhu Le, British Columbia Cancer Agency.
Conflict of interest: none declared.
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