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Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer
Koutros, Stella1; Freeman, Laura E. Beane; Berndt, Sonja I.; Andreotti, Gabriella; Lubin, Jay H.; Sandler, Dale P.2; Hoppin, Jane A.2; Yu, Kai; Li, Qizhai3; Burdette, Laura A.4; Yuenger, Jeffrey4; Yeager, Meredith4; Alavanja, Michael C. R.
2010-11-15
Source PublicationCANCER RESEARCH
ISSN0008-5472
Volume70Issue:22Pages:9224-9233
AbstractGenome-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); 9224-33. (C) 2010 AACR.
DOI10.1158/0008-5472.CAN-10-1078
Language英语
Funding ProjectNIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics[Z01CP010119] ; National Institute of Environmental Health Sciences[Z01ES049030]
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000284213300028
PublisherAMER ASSOC CANCER RESEARCH
Citation statistics
Document Type期刊论文
Identifierhttp://ir.amss.ac.cn/handle/2S8OKBNM/9384
Collection系统科学研究所
Corresponding AuthorKoutros, Stella
Affiliation1.NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA
2.Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA
3.Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing, Peoples R China
4.NCI, Core Genotyping Facil, Adv Technol Program, Frederick, MD 21701 USA
Recommended Citation
GB/T 7714
Koutros, Stella,Freeman, Laura E. Beane,Berndt, Sonja I.,et al. Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer[J]. CANCER RESEARCH,2010,70(22):9224-9233.
APA Koutros, Stella.,Freeman, Laura E. Beane.,Berndt, Sonja I..,Andreotti, Gabriella.,Lubin, Jay H..,...&Alavanja, Michael C. R..(2010).Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer.CANCER RESEARCH,70(22),9224-9233.
MLA Koutros, Stella,et al."Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer".CANCER RESEARCH 70.22(2010):9224-9233.
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