Fonofos Exposure and Cancer Incidence in the Agricultural Health Study

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20852, USA.
Environmental Health Perspectives (Impact Factor: 7.98). 01/2007; 114(12):1838-42. DOI: 10.1289/ehp.9301
Source: PubMed


The Agricultural Health Study (AHS) is a prospective cohort study of licensed pesticide applicators from Iowa and North Carolina enrolled 1993-1997 and followed for incident cancer through 2002. A previous investigation in this cohort linked exposure to the organophosphate fonofos with incident prostate cancer in subjects with family history of prostate cancer.
This finding along with findings of associations between organophosphate pesticides and cancer more broadly led to this study of fonofos and risk of any cancers among 45,372 pesticide applicators enrolled in the AHS.
Pesticide exposure and other data were collected using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RRs) and 95% confidence intervals (CIs) while controlling for potential confounders.
Relative to the unexposed, leukemia risk was elevated in the highest category of lifetime (RR = 2.24; 95% CI, 0.94-5.34, Ptrend = 0.07) and intensity-weighted exposure-days (RR = 2.67; 95% CI, 1.06-6.70, Ptrend = 0.04), a measure that takes into account factors that modify pesticide exposure. Although prostate cancer risk was unrelated to fonofos use overall, among applicators with a family history of prostate cancer, we observed a significant dose-response trend for lifetime exposure-days (Ptrend = 0.02, RR highest tertile vs. unexposed = 1.77, 95% CI, 1.03-3.05; RRinteraction = 1.28, 95% CI, 1.07-1.54). Intensity-weighted results were similar. No associations were observed with other examined cancer sites.
Further study is warranted to confirm findings with respect to leukemia and determine whether genetic susceptibility modifies prostate cancer risk from pesticide exposure.

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Available from: Michael C Alavanja,
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    • "Findings for pesticides and other agricultural exposures and cancer include several aspects of prostate cancer (family history, aggressive prostate cancer, genetic polymorphisms) [Alavanja et al., 2003; Koutros et al., 2011, 2013], contact with farm animals [Beane et al., 2012], monoclonal gammopathy of undetermined significance [Landgren et al., 2009], telomere length [Hou et al., 2013], and childhood cancer among children of pesticide applicators [Flower et al., 2004]. Many individual pesticides have been evaluated for cancer risk in human studies, some for the first time in the AHS, including atrazine [Beane et al., 2011], glyphosate [De Roos et al., 2005], diazinon [Beane et al., 2005], pendimethalin [Hou et al., 2006], metolachlor [Rusiecki et al., 2006], dicamba [Samanic et al., 2006], fonofos [Mahajan et al., 2006], organochlorine pesticides [Purdue et al., 2007], malathion [Bonner et al., 2007], dichlorvos [Koutros et al., 2008], permethrin [Rusiecki et al., 2009], metribuzin [Delancey et al., 2009], coumaphos [Christensen et al., 2010], and terbufos [Bonner et al., 2010]. "
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    ABSTRACT: Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures. Am. J. Ind. Med. 58:113–122, 2015.
    American Journal of Industrial Medicine 02/2015; 58(2):113-122. DOI:10.1002/ajim.22403 · 1.74 Impact Factor
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    • "In the Agricultural Health Study (AHS), a significant excess of prostate cancer was observed among private and commercial pesticide applicators compared to the general population [3] [4]. Also, use of pesticides, such as phorate [5], fonofos [6], butylate [7], and coumaphos [8], has been linked with an increased risk of prostate cancer among AHS participants with a family history of prostate cancer. We conducted a prostate cancer nested case-control study within the AHS to examine interactions between prespecified genetic pathways and pesticide exposure. "
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    ABSTRACT: Background. Lipid metabolism processes have been implicated in prostate carcinogenesis. Since several pesticides are lipophilic or are metabolized via lipid-related mechanisms, they may interact with variants of genes in the lipid metabolism pathway. Methods. In a nested case-control study of 776 cases and 1444 controls from the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators, we examined the interactions between 39 pesticides (none, low, and high exposure) and 220 single nucleotide polymorphisms (SNPs) in 59 genes. The false discovery rate (FDR) was used to account for multiple comparisons. Results. We found 17 interactions that displayed a significant monotonic increase in prostate cancer risk with pesticide exposure in one genotype and no significant association in the other genotype. The most noteworthy association was for ALOXE3 rs3027208 and terbufos, such that men carrying the T allele who were low users had an OR of 1.86 (95% CI = 1.16-2.99) and high users an OR of 2.00 (95% CI = 1.28-3.15) compared to those with no use of terbufos, while men carrying the CC genotype did not exhibit a significant association. Conclusion. Genetic variation in lipid metabolism genes may modify pesticide associations with prostate cancer; however our results require replication.
    Journal of Cancer Epidemiology 08/2012; 2012:358076. DOI:10.1155/2012/358076
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    • "Although the registrant for fonofos voluntarily canceled the chemical's registration in 1998 (U.S. Environmental Protection Agency 1999), fonofos was used by about 25% of the nested case–control study participants and thus may have contributed to prostate cancer risk in our study population. Supporting our NEIL3 inter action finding, fonofos has previously been associated with prostate cancer in the AHS among participants with a family history of prostate cancer (Alavanja et al. 2003; Mahajan et al. 2006), which suggested a role of genetic susceptibility to carcinogenic effects of this chemical. There is also some plausibility for our interaction findings between carbofuran and EPTC "
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    ABSTRACT: Previous research indicates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, evidence suggests a role of oxidative DNA damage. Because base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated interactions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of white Agricultural Health Study (AHS) pesticide applicators. We used likelihood ratio tests from logistic regression models to determine p-values for interactions between three-level pesticide exposure variables (none/low/high) and SNPs (assuming a dominant model), and the false discovery rate (FDR) multiple comparison adjustment approach. The interaction between fonofos and rs1983132 in NEIL3 [nei endonuclease VIII-like 3 (Escherichia coli)], which encodes a glycosylase that can initiate BER, was the most significant overall [interaction p-value (pinteract) = 9.3 × 10-6; FDR-adjusted p-value = 0.01]. Fonofos exposure was associated with a monotonic increase in prostate cancer risk among men with CT/TT genotypes for rs1983132 [odds ratios (95% confidence intervals) for low and high use compared with no use were 1.65 (0.91, 3.01) and 3.25 (1.78, 5.92), respectively], whereas fonofos was not associated with prostate cancer risk among men with the CC genotype. Carbofuran and S-ethyl dipropylthiocarbamate (EPTC) interacted similarly with rs1983132; however, these interactions did not meet an FDR < 0.2. Our significant finding regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk.
    Environmental Health Perspectives 08/2011; 119(12):1726-32. DOI:10.1289/ehp.1103454 · 7.98 Impact Factor
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