Reference
Hohenadel K, Harris SA, McLaughlin JR, et al. Exposure to multiple pesticides and risk of non-Hodgkin lymphoma in men from six canadian provinces. Int J Environ Res Public Health. 2011;8:2320-2330.
Design
A case-control study using multiple logistic regression analysis to assess the relationship between the number of pesticides used and ensuing risk of developing non-Hodgkin lymphoma (NHL). Exposure data was gotten from the Cross-Canada Study of Pesticides and Health, gathered between 1991 and 1994. Ensuing cases of NHL were found through hospital records or cancer registries. Medical and occupational history, demographic characteristics, and other possible confounding factors were gathered from all participants through a validated postal questionnaire. Those participants indicating more than 10 hours of pesticide use during their lifetime underwent a phone interview for details. Fifteen percent of those with less than 10 hours exposure over their lives were also randomly interviewed by phone. Due to limited sample size, dose and duration data was not used to stratify risk categories, only the total number of pesticide exposures.
Participants
Canadian men 19 years of age and older from 6 Canadian provinces (ie, Alberta, British Columbia, Manitoba, Ontario, Quebec, Saskatchewan) (n=513), all of whom were part of the Cross-Canada Study of Pesticides and Health. Control group (n=1,506) was assembled using provincial health records, telephone listings or voter lists. Controls were matched by age (within 2 years) and province.
Key Findings
The risk of NHL increased with the number of pesticides used. When pesticides were broken into subgroups of herbicides, insecticides, and fungicides, this association remained. For subgroups, the highest use category compared to no use rendered the following odds ratios:
- Pesticides: OR=1.63 (95% CI: 1.20-2.21, P[trend]=0.04)
- Herbicides: OR=1.57 (95% CI: 0.96-2.97, P[trend]=0.02)
- Insecticides: OR=1.70 (95% CI: 0.95-3.05, P[trend] <0.01)
- Fungicides: OR=1.72 (95% CI: 1.07-2.77, P[trend]=0.04).
By pesticide category, odds ratios tended highest for the use of 2 or more phenoxy herbicides: OR=1.36 (95% CI: 0.92-2.02, P[trend] =0.15; organophosphates: OR=1.69 (95% CI: 1.04-2.74, P[trend]<0.01; or organochlorines: OR=1.36 (95% CI: 0.92-2.02, P[trend]=0.15).
When analysis was restricted to only “potentially carcinogenic” pesticides, odds ratios were as follows (overall P[trend]=0.01):
- 1 pesticide: OR=1.30 (95% CI, 0.90-1.88)
- 2-4 pesticides: OR=1.54 (95% CI: 1.11-2.12)
- 5 or more pesticides: OR=1.94 (95% CI: 1.17-3.23)
Of note, these increases in odds ratios are “greater than any produced when examining use of any single pesticide.” Confounders such as ultraviolet rays, farm animals, and diesel exhaust did not significantly impact the odds ratios. Separately, malathion in combination with several different pesticides was associated with elevated risk.
Practice Implications
Higher rates of NHL in agricultural workers and other applicators of pesticides has long been known. Specifically, exposures to phenoxy herbicides, oraganochlorines, organohosphates, and carbamate pesticides have been implicated in the development of NHL. Despite this association, data implicating each chemical is not consistent.1 However, as is customary, the toxicity of these compounds has mostly been assessed as individual agents. Associated risk of NHL with exposures to multiple pesticides has undergone very little scrutiny, despite the fact that this more accurately reflects real-world situations.
This publication by Hohenadel and colleagues corroborates 2 previous studies that concluded multiple exposures of pesticides may have a more detrimental effect than single exposure toxicology implies. In 2001, McGuffie and colleagues published the results of The Cross-Canada Study of Pesticides and Health. Risk of NHL increased significantly for many compounds when looked at as single agent exposures, including a doubling of risk for compounds such as mecoprop (OR=2.22; 95% CI, 1.58-3.44), carbaryl (OR=2.11; 95% CI, 1.21-3.69), and carbon tetrachloride (OR=2.42; 95% CI, 1.19-5.14). Mixtures containing aldrin were associated with the highest risk (OR=3.42; 95% CI, 1.19-9.95).2 A 2003 publication by DeRoos and colleagues used a pooled analysis of data derived from 3 National Cancer Institute case control studies done in the 1980s. This pooling gave a cumulative total of 3,417 farm workers throughout Nebraska, Minnesota, Kansas, and Iowa. His group found exposure to “several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate.” A subanalysis of these “potentially carcinogenic” pesticides suggested a positive trend of risk with exposure to increasing numbers of compounds.3
A meta-analysis of case-control studies in 2007 showed that “there is a significantly positive association between occupational exposure to pesticides and all hematopoietic cancers as well as NHL.”4 While it is assumed that multiple pesticide exposures may be the cause of this association, studies documenting exposure type and duration in assessing NHL risk are needed to stratify which agents, or combinations of agents, are most implicated in causation. To date, the evidence is inadequate for the Environmental Protection Agency to declare that multiple pesticide exposures increase the risk of NHL.
While many of the readers of this journal may already be informing their patients to avoid pesticides, studies such as this can be used to overcome the complacency that appears to surround the use of pesticides.
As practitioners, it is essential that we attend to the health of our patients by educating them on how to reduce risk for later disease. While many of the readers of this journal may already be informing their patients to avoid pesticides, studies such as this can be used to overcome the complacency that appears to surround the use of pesticides. The EPA estimates that approximately 100 million pounds of these types of pesticides are used annually in the United States.5
In addition to the association of pesticide use with NHL development, there is also an increased risk associated when there is a family history of any hematopoietic malignancies (eg, lymphomas, multiple myeloma, leukemias). Relative risk of NHL is higher for siblings (OR for NHL=3.2, 95% CI=1.3-7.6) or children of those with a hematopoietic malignancy (OR=1.6, 95% CI=1.1-2.3).6 Given this information, our patients with a family history of any hematopoietic malignancy should be considered at higher risk and protective measures including pesticide avoidance should be strongly encouraged.
Study Limitations
The most limiting factor of this study is the variability in recall bias. It is possible that the control group, given no diagnosis of NHL, did not consider their exposures as carefully as individuals with NHL. Nonetheless, the data is consistent and compelling and this limitation should not sway our use of the precautionary principle when dealing with pesticides.
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