An Evaluation Of Potentially Carcinogenic Pesticides And The Risks Of Non-Hodgkin Lymphoma (NHL) And Its Histological Sub-Types: An Analysis Of The North American Pooled Project (NAPP)

Shelley HARRIS, Dalla Lana School of Public Health, University of Toronto, Canada
MUSA R. 2,3 , PAHWA M. 1,2 , KACHURI L. 1,2,3,4 , SPINELLI J. 5 , BLAIR A. 6 , PAHWA P. 8 , MCLAUGHLIN J. 1,3,4,9 , DOSMAN J. 8 , HOAR ZAHM S. 6 , CANTOR K. 6 , WEISENBURGER D. 7 , BEANE FREEMAN L. 6

1 Occupational Cancer Research Centre, Cancer Care Ontario, Toronto, ON, Canada
2 Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON, Canada
3 Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
4 Lunenfeld-Tanenbaum Research Institute, Toronto, ON, Canada
5 British Columbia Cancer Agency Research Centre, University of British Columbia, Vancouver, BC, Canada
6 U.S. National Cancer Institute, Bethesda, MD, USA
7 Department of Pathology, City of Hope Medical Center, Duarte, CA, USA
8 University of Saskatchewan, Saskatoon, SK, Canada
9 Public Health Ontario, Toronto, ON, Canada

Purpose:  The International Agency for Research on Cancer (IARC) has classified numerous pesticides as possibly or probably carcinogenic.  The purpose of this work was to investigate associations between carcinogenic pesticide use and the risks of NHL sub-types in the North American Pooled Project (NAPP).

Methods: The NAPP included 1690 NHL cases and 5131 controls from six Canadian provinces, and four Midwestern U.S. states. Pesticides were assigned a carcinogenic probability score (ranging from 0.1-1.0) based on a synthesis of assessments by IARC and the US Environmental Protection Agency.  Nineteen pesticides were classified as “probably” carcinogenic (score ≥0.6) and 35 were “possibly” (score ≥0.5) carcinogenic. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression for NHL overall,  and for follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), small lymphocytic lymphoma (SLL), and other.

Results:  Compared to unexposed subjects, use of ≥5 pesticides (carcinogenic probability ≥0.5) was associated with significantly higher risks of NHL (OR=1.71, 95%CI:1.37-2.12; p-trend<0.0001). Similar positive trends in risk were observed for the use of ≥5 insecticides (carcinogenic probability ≥0.5) for NHL (OR=1.80, 95% CI:1.26-2.55), FL (OR=1.98, 95%CI:1.19-3.30), SLL (OR=2.34, 95% CI:1.10-5.00) and other (OR=1.41, 95% CI:0.69-2.88). Exposure to probably carcinogenic fungicides was associated with NHL overall (OR=1.90, 95%CI:1.22-2.95), DLBCL (OR=2.30, 95%CI:1.26-4.20), and other sub-types (OR=2.81, 95%CI:1.39-5.68). Dose-response relationships were attenuated for the herbicides, however use of 1 herbicide (carcinogenic probability ≥0.6) was associated with significantly higher odds of NHL (OR=1.28, 95%CI:1.02-1.60) and DLBCL (OR=1.51, 95% CI:1.11-2.07).
 
Conclusions: The risk of NHL and its subtypes increased significantly with the use of a greater number of potentially carcinogenic insecticides, fungicides and herbicides. The exposure response trends were quite striking and support of the hazard assessments of these agencies.

Funding source: Canadian Cancer Society Research Institute (#703055); U.S. National Institutes of Health Intramural Research Program, National Cancer Institute.