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Joint associations between established genetic susceptibility loci, pesticide exposures, and risk of prostate cancer.
Hurwitz, Lauren M; Beane Freeman, Laura E; Andreotti, Gabriella; Hofmann, Jonathan N; Parks, Christine G; Sandler, Dale P; Lubin, Jay H; Liu, Jia; Jones, Kristine; Berndt, Sonja I; Koutros, Stella.
Afiliação
  • Hurwitz LM; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA. Electronic address: lauren.hurwitz@nih.gov.
  • Beane Freeman LE; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA.
  • Andreotti G; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA.
  • Hofmann JN; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA.
  • Parks CG; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.
  • Sandler DP; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.
  • Lubin JH; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA.
  • Liu J; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA; Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD
  • Jones K; Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA; Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD
  • Berndt SI; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA.
  • Koutros S; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA.
Environ Res ; 237(Pt 2): 117063, 2023 Nov 15.
Article em En | MEDLINE | ID: mdl-37659638
ABSTRACT
More than 200 genetic variants have been independently associated with prostate cancer risk. Studies among farmers have also observed increased prostate cancer risk associated with exposure to specific organophosphate (fonofos, terbufos, malathion, dimethoate) and organochlorine (aldrin, chlordane) insecticides. We examined the joint associations between these pesticides, established prostate cancer loci, and prostate cancer risk among 1,162 cases (588 aggressive) and 2,206 frequency-matched controls nested in the Agricultural Health Study cohort. History of lifetime pesticide use was combined with a polygenic risk score (PRS) generated using 256 established prostate cancer risk variants. Logistic regression models estimated the joint associations of the pesticides, the PRS, and the 256 individual genetic variants with risk of total and aggressive prostate cancer. Likelihood ratio tests assessed multiplicative interaction. We observed interaction between ever use of fonofos and the PRS in relation to total and aggressive prostate cancer risk. Compared to the reference group (never use, PRS < median), men with ever use of fonofos and PRS > median had elevated risks of total (OR 1.35 [1.06-1.73], p-interaction = 0.03) and aggressive (OR 1.49 [1.09-2.04], p-interaction = 0.19) prostate cancer. There was also suggestion of interaction between pesticides and individual genetic variants occurring in regions associated with DNA damage response (CDH3, EMSY genes) and with variants related to altered androgen receptor-driven transcriptional programs critical for prostate cancer. Our study provides evidence that men with greater genetic susceptibility to prostate cancer may be at higher risk if they are also exposed to pesticides and suggests potential mechanisms by which pesticides may increase prostate cancer risk.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2023 Tipo de documento: Article