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Prevention and Epidemiology

Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer

Stella Koutros, Laura E. Beane Freeman, Sonja I. Berndt, Gabriella Andreotti, Jay H. Lubin, Dale P. Sandler, Jane A. Hoppin, Kai Yu, Qizhai Li, Laura A. Burdette, Jeffrey Yuenger, Meredith Yeager and Michael C.R. Alavanja
Stella Koutros
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Laura E. Beane Freeman
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Sonja I. Berndt
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Gabriella Andreotti
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Jay H. Lubin
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Dale P. Sandler
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Jane A. Hoppin
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Kai Yu
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Qizhai Li
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Laura A. Burdette
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Jeffrey Yuenger
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Meredith Yeager
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Michael C.R. Alavanja
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DOI: 10.1158/0008-5472.CAN-10-1078
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Abstract

Genome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In the Agricultural Health Study, a prospective study of licensed pesticide applicators, we observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, we evaluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors estimated odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, 49 pesticides, and prostate cancer risk in 776 cases and 1,444 controls. The ORs for a previously identified variant, rs4242382, and prostate cancer increased significantly (P < 0.05) with exposure to the organophosphate insecticide fonofos, after correction for multiple testing, with per allele ORnonexposed of 1.17 (95% CI, 0.93–1.48), per allele ORlow of 1.30 (95% CI, 0.75–2.27), and per allele ORhigh of 4.46 (95% CI, 2.17–9.17; P-interaction = 0.002, adjusted P-interaction = 0.02). A similar effect modification was observed for three other organophosphate insecticides (coumaphos, terbufos, and phorate) and one pyrethroid insecticide (permethrin). Among ever users of fonofos, subjects with three or four risk alleles at rs7837328 and rs4242382 had approximately three times the risk of prostate cancer (OR, 3.14; 95% CI, 1.41–7.00) compared with subjects who had zero risk alleles and never used fonofos. We observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk. Cancer Res; 70(22); OF1–10. ©2010 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received April 2, 2010.
  • Revision received September 15, 2010.
  • Accepted September 15, 2010.
  • ©2010 American Association for Cancer Research.
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Published OnlineFirst October 26, 2010
doi: 10.1158/0008-5472.CAN-10-1078

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Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer
Stella Koutros, Laura E. Beane Freeman, Sonja I. Berndt, Gabriella Andreotti, Jay H. Lubin, Dale P. Sandler, Jane A. Hoppin, Kai Yu, Qizhai Li, Laura A. Burdette, Jeffrey Yuenger, Meredith Yeager and Michael C.R. Alavanja
Cancer Res October 26 2010 DOI: 10.1158/0008-5472.CAN-10-1078

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Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer
Stella Koutros, Laura E. Beane Freeman, Sonja I. Berndt, Gabriella Andreotti, Jay H. Lubin, Dale P. Sandler, Jane A. Hoppin, Kai Yu, Qizhai Li, Laura A. Burdette, Jeffrey Yuenger, Meredith Yeager and Michael C.R. Alavanja
Cancer Res October 26 2010 DOI: 10.1158/0008-5472.CAN-10-1078
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