The association between exposure to ambient air pollution and risk of Leukemia in Canada

Exposure to air pollutants, including nitrogen dioxide (NO2) and particulate matter smaller than 2.5 microns (PM2.5), have been shown to be associated with increased incidence of lung cancer, and a few recent reports found that the incidence of breast and prostate cancer may also be so related. There is, however, a paucity of studies on other sites of cancer, including adult leukemia. Occupational studies have shown that exposure to benzene increases one’s risk of developing leukemia, and ambient air contains benzene and other carcinogens. As ambient air pollution contains benzene, has been shown to have causal associations with cancer of the lung, and may have associations in other organs, there is a possibility that leukemia could also be associated with exposure to air pollution. My review of the literature indicated a possible association between leukemia in children and NO2. However, the available studies were limited by small numbers of cases, low and unreported response rates, and potential misclassification of exposures. In addition, only five studies were used to investigate leukemia in adults. The objective of this thesis was to determine whether ambient air pollution is associated with incidence of leukemia in adults. We used a Canadian population-based case-control study conducted in 1994-1997. Cases were 1,064 adults with incident leukemia and controls were 5,039 adults without any cancer. Using data from remote-sensing stations across Canada, we developed interpolation models to assign subjects’ past exposure to NO2 and PM2.5 from 1975-1994. We used the total average exposure of a subject between the 1975-1994 period and we assigned these estimates to their place of residence. We conducted sub-analyses for individual provinces (Ontario, British Columbia, Alberta) and for individual subtypes where numbers were sufficient (chronic and acute myeloid leukemia, and chronic lymphocytic leukemia). Using logistic regression models using natural cubic splines, we found a ‘n-shaped’ response function between exposure to NO2 and all forms of leukemia: at low concentrations, from 4.51 to 14.66 ppb, the odds ratio (OR) was 1.24 (95% confidence interval (CI) 1.00-1.54) and at higher concentrations, from 22.75 to 29.7 ppb, the OR was 0.81 (95% CI 0.69 – 0.95). For PM2.5 we found a concentration-response function that was consistent with a slight monotonic increase: at lower concentrations of PM2.5, from 5.6 to 8.0 μg/m3, the OR was 0.89 (95% CI 0.76 – 1.03) and at higher concentrations, from 15.6 to 19.2 μg/m3, the OR was 1.20 (95% CI 0.96 – 1.51). For chronic lymphocytic leukemia we found an OR per 5 ppb of NO2 of 0.92 (95% CI 0.86 – 1.00) and an OR per 10 μg/m3 of PM2.5 of 0.63 (95% CI 0.42 – 0.94). We found no association for exposure to PM2.5. The n-shaped curve for NO2 may be related to urban-rural differences and/or to possible selection bias. From this thesis it is clear that given the dearth of studies in adult leukemia further research is needed.

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