Pre-diagnostic Serum Concentrations of Organochlorines and Risk of Myeloid Leukemia: a Nested Case-Control Study in the Norwegian Janus Serum Bank Cohort

Abstract

Introduction: Organochlorines (OCs) are structurally diverse and environmentally persistent chemicals that are widespread contaminants. Some OC pesticides and polychlorinated biphenyl (PCBs) congeners have been associated with lymphoid neoplasms. While an association between OC exposure and risk of myeloid leukemia (ML) is biologically plausible and suggestive based on observations in occupationally exposed individuals, associations between serum levels of OCs and risk of ML in the general population have not been evaluated prospectively. Methods: We conducted a nested case-control study within the Janus cohort, a population-based biobank consisting of serum samples collected in the time period 1972-2004 from ~318,000 individuals in Norway. Risk of ML in relation to lipid-adjusted levels of 11 OC pesticide metabolites and 34 PCB congeners was evaluated in 76 ML cases and 353 controls. Odds ratios (ORs) and 95% confidence intervals (CI) were computed and associations were adjusted for sex, county, age and date at blood draw, smoking, and BMI. Results: Higher levels of total chlordane/heptachlor metabolites were associated with future risk of ML in continuous (OR = 1.2, 95% CI = 1.0-1.5 per unit increase in the log-transformed concentration (ng/g lipid)) and tertile analyses (3rd vs. 1st tertile OR = 2.0, 95% CI = 0.9-4.6). The association was strongest for oxychlordane (OR = 1.9, 95% CI = 1.2-2.9 per unit increase in the log-transformed concentration (ng/g lipid); 3rd vs. 1st tertile OR = 2.2, 95% CI = 1.0-4.9), and a suggestive association with ML risk was also observed for higher levels of heptachlor epoxide (3rd vs. 1st tertile OR = 2.0, 95% CI = 0.9-4.5). No consistent associations with ML risk were observed for other OC pesticide metabolites or for PCBs. Conclusions: Our data provide evidence that metabolites of chlordane/heptachlor may be associated with future risk of ML. Studies with a larger number of ML cases are needed to follow-up on these findings.