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North American Pooled Project: pesticides, agricultural exposures, and cancer

Purpose

The overall objective of the North American Pooled Project is to assess the effects of exposure to specific pesticides and other agricultural factors in association with different cancer types.

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Background

The prevalence of certain cancers is elevated in farmers and agricultural populations (Blair et al., 1992; Blair et al., 1987). The exact causes are not known, and many studies have been done to identify potential risk factors. A series of studies was conducted in the U.S. and Canada during the 1980s and 1990s. The U.S. National Cancer Institute (NCI) led three case-control studies in four mid-western states to assess the effects of pesticides and other agricultural exposures on the risks of non-Hodgkin lymphoma, Hodgkin lymphoma, soft tissue sarcoma, and multiple myeloma (Cantor et al., 1992; Hoar et al., 1986; Brown et al., 1990; Zahm et al., 1990). A similar case-control study, called the Cross-Canada Study of Pesticides and Health (CCSPH), was completed in six Canadian provinces during the 1990s (McDuffie et al., 2001).

These studies have each produced rich datasets and many interesting associations have been observed. For instance, the risk of non-Hodgkin lymphoma was found to increase from the self-reported use of specific pesticides (Cantor et al., 1992; Hoar et al., 1986; Zahm et al., 1990; McDuffie et al., 2001), an increasing number of potentially carcinogenic pesticides (De Roos et al., 2003; Hohenadel et al., 2011), and some commonly used pesticide combinations (De Roos et al., 2003; Hohenadel et al., 2011). Other agricultural exposures, like diesel exhaust (McDuffie et al., 2002), and non-occupational risk factors, such as certain genetic abnormalities (Chiu & Blair, 2009), also increased the odds of non-Hodgkin lymphoma. These findings demonstrate that the causes of these types of cancer are complex. Click here for a summary of the OCRC’s research using CCSPH data.

In order to evaluate associations between agricultural exposures and the risks of non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, and soft tissue sarcoma among Canadian and American men, the U.S. NCI case-control datasets were harmonized, or “pooled”, with the CCSPH dataset. This initiative, called the North American Pooled Project (NAPP), provides an excellent opportunity to overcome some of the challenges of previous studies, particularly the small number of cases that have limited the strength and consistency of associations.

Methods

We have taken advantage of the larger sample size of this joint project to evaluate interactions between multiple pesticides, examine other factors that may interact with pesticide exposure to affect cancer risk, and conduct separate analyses for various agricultural exposures and cancer sub-types. We adjusted analyses for specific confounders, such as demographics, medical history, family history of cancer, lifetime job history, occupational exposure to pesticides, use of personal protective equipment, and tobacco use.

Analyses of the NAPP are a collaborative effort between the U.S. NCI and OCRC. Support has been obtained from the original investigators of the individual case-control studies and from the U.S. NCI and OCRC to harmonize and analyze the data. Both the OCRC and U.S. NCI have contributed to data analysis and the development of manuscripts. Researchers from institutions other than the OCRC and U.S. NCI are welcome to submit proposals (please see below).

Workshop

Cancer Care Ontario and the OCRC hosted a workshop in Toronto on May 27, 2013 in order to identify research priorities using data available in the NAPP and to brainstorm potential inputs for a future knowledge transfer and exchange strategy for the NAPP. This workshop was part of a knowledge dissemination grant funded by the Canadian Institutes for Health Research.

Twenty-two participants attended the workshop with expertise in broad areas including cancer epidemiology, agricultural extension, pesticide exposure assessment, toxicology, risk assessment, regulation, knowledge translation and exchange, and policy. Workshop discussions were facilitated and a step-wise method was used to identify research priorities. Examples of knowledge dissemination in the field and industry perspectives on epidemiological research on pesticides were presented. The workshop strengthened partnerships between researchers and stakeholders and participants emerged with a greater understanding of the NAPP. The NAPP research team reviewed the workshop report and all workshop participants were invited to provide their edits and feedback. The final report can be found here.

Research proposals

The NAPP Executive Committee is currently developing guidelines for submitting and approving proposals to conduct analyses using data from the NAPP. The guidelines will be posted here shortly. In the meantime, if you are interested in learning more about the data and how to access it, please contact the OCRC.

Implications

The NAPP is a large pooled case-control study of pesticides, agricultural exposures, and non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, and soft tissue sarcoma. The results that will emerge from this study will contribute to our understanding of these associations. As the NAPP is in its formative stages, the early and meaningful engagement of stakeholders will support ongoing dissemination of relevant research. This research may ultimately inform efforts that reduce exposure to agricultural factors that are known or suspected to cause cancer.

Executive Committee
Shelley A. Harris
OCRC and University of Toronto
Laura Beane Freeman
U.S. National Cancer Institute
John J. Spinelli
British Columbia Cancer Agency Research Centre, University of British Columbia, Simon Fraser University
Research Team
Shelley A. Harris
OCRC and University of Toronto
Laura Beane Freeman
U.S. National Cancer Institute
John J. Spinelli
British Columbia Cancer Agency Research Centre, University of British Columbia, Simon Fraser University
Aaron Blair
U.S. National Cancer Institute
Manisha Pahwa
OCRC
Linda Kachuri
OCRC, University of Toronto, Lunenfeld-Tanenbaum Research Institute
Paul Demers
OCRC and University of Toronto
Stella Koutros
U.S. National Cancer Institute
Lidija Latifovic
OCRC
Shelia Hoar Zahm
U.S. National Cancer Institute
Kenneth P. Cantor
U.S. National Cancer Institute
Dennis D. Weisenburger
City of Hope Medical Center
John McLauglin
Public Health Ontario, University of Toronto
Punam Pahwa
Canadian Centre for Health and Safety in Agriculture, University of Saskatchewan
James A. Dosman
Canadian Centre for Health and Safety in Agriculture, University of Saskatchewan
References

Blair A, Zahm SH, Pearce NE, Heineman EF, Fraumeni JF Jr. Clues to cancer etiology from studies of farmers. Scand J Work Environ Health 1992;18:209-215.

Blair A, McDuffie HH, Dosman JA. Cancer in rural areas. CMAJ 1987;136:924-5.

Cantor KP, Blair A, Everett G, Gibson R, Burmeister LF, Brown LM, Schuman L, Dick FR. Pesticides and other agricultural risk factors for non-Hodgkin’s lymphoma among men in Iowa and Minnesota. Cancer Res 1992;52:2447-55.

Hoar SK, Blair A, Holmes FF, Boysen CD, Robel RJ, Hoover R, Fraumeni JF Jr. Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. JAMA 1986;256:1141-7.

Brown LM, Blair A, Gibson R, Everett GD, Cantor KP, Schuman LM, Burmeister LF, Van Lier SF, Dick F. Pesticide exposures and other agricultural risks factors for leukemia among men in Iowa and Minnesota. Cancer Res 1990;50:6585-91.

Zahm SH, Weisenburger DD, Babbitt PA, Saal RC, Vaught JB, Cantor KP, Blair A. A case-control study of non-Hodgkin’s lymphoma and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska. Epidemiology 1990;1:349-56.

McDuffie HH, Pahwa P, McLaughlin JR, Spinelli JJ, Fincham S, Dosman JA, Robson D, Skinnider LF, Choi NW. Non-Hodgkin’s lymphoma and specific pesticide exposures in men: Cross-Canada Study of Pesticides and Health. Cancer Epidemiology, Biomarkers & Prevention 2001;10:1155-1163.

DeRoos AJ, Zahm SH, Cantor KP, Weisenburger DD, Holmes FF, Burneister LF, Blair AE. Integrative assessment of multiple pesticides as risk factors for non-Hodgkin’s lymphoma among men. Occup Environ Med. 2003, 60, e11.

Hohenadel K, Harris SA, McLaughlin JM, Spinelli JJ, Pahwa P, Dosman JA, Demers PA, Blair A. Exposure to multiple pesticides and risk of non-Hodgkin lymphoma in men from six Canadian provinces. International Journal of Environmental Research and Public Health 2011;8:2320-2330.

McDuffie HH, Pahwa P, Spinelli JJ, McLaughlin JR, Fincham S, Robson D, Dosman JA, Hu J. Canadian male farm residents, pesticide safety handling practices, exposure to animals and non-Hodgkin’s lymphoma (NHL). American Journal of Industrial Medicine 2002;Supplement 2:54-61.

Chiu BC-H, Blair A. Pesticides, chromosomal aberrations, and non-Hodgkin’s lymphoma. Journal of Agromedicine 2009;14:250-255.