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      Plasma Organochlorines and Subsequent Risk of Prostate Cancer in Japanese Men: A Nested Case–Control Study

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          Abstract

          Background

          Although accumulating evidence suggests that exposure to organochlorine pesticides and polychlorinated biphenyls (PCBs) may contribute to the development of prostate cancer, few investigations have used biological samples to classify exposure to specific organochlorines. To our knowledge, this is the first prospective study to investigate the association between blood levels of organochlorines and prostate cancer risk.

          Methods

          We conducted a nested case–control study using data from the Japan Public Health Center–based Prospective (JPHC) Study. A total of 14,203 men 40–69 years old who returned the baseline questionnaire and who provided blood samples were followed from 1990 to 2005. Using a mean follow-up period of 12.8 years, we identified 201 participants who were newly diagnosed with prostate cancer. Two matched controls for each case were selected from the cohort. We used a conditional logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer in relation to plasma levels of nine organochlorines: PCBs, dichlorodiphenyltrichloroethane (DDT), hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), trans- and cis-nonachlor, oxychlordane, and mirex.

          Results

          No statistically significant association with total prostate cancer was seen for any plasma organochlorine, although we did observe an insignificant inverse association for plasma HCB and β-HCH. Total PCB in plasma was also inversely associated with advanced prostate cancer but without statistical significance.

          Conclusion

          Our results suggest that no overall association exists between prostate cancer and organochlorines at the levels measured in our study population.

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          Most cited references53

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          Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist.

          The increase in the number of reports of abnormalities in male sex development in wildlife and humans coincided with the introduction of 'oestrogenic' chemicals such as DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) into the environment. Although these phenotypic alterations are thought to be mediated by the oestrogen receptor, they are also consistent with inhibition of androgen receptor-mediated events. Here we report that the major and persistent DDT metabolite, p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), has little ability to bind the oestrogen receptor, but inhibits androgen binding to the androgen receptor, androgen-induced transcriptional activity, and androgen action in developing, pubertal and adult male rats. The results suggest that abnormalities in male sex development induced by p,p'-DDE and related environmental chemicals may be mediated at the level of the androgen receptor.
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            Chlorinated hydrocarbon levels in human serum: effects of fasting and feeding.

            Twenty healthy adult humans had serum samples drawn on four occasions within a 24-hr period: after a 12 hr overnight fast, 4-5 hr after a high fat breakfast, at midafternoon, and the next morning after another 12 hr fast. Nonfasting samples had 22% to 29% higher mean concentrations (p less than 0.05) than did fasting samples for polychlorinated biphenyls (PCBs, 4.81 vs 3.74 ng/g serum wt), hexachlorobenzene (HCB, 0.163 vs 0.134 ng/g serum wt), and p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE, 6.74 vs 5.37 ng/g serum wt) measured by electron capture gas liquid chromatography. Total serum lipids were estimated from measurements of total cholesterol, free cholesterol, triglycerides, and phospholipids and were 20% higher in nonfasting samples than in fasting samples (7.05 g/L vs 5.86 g/L). When PCBs, HCB, and p,p'-DDE concentrations were corrected by total serum lipids, results from fasting and non-fasting samples were not statistically different. Because of the differences in these chlorinated hydrocarbon concentrations observed with different sample collection regimens, meaningful comparison of analytical results requires standardizing collection procedures or correcting by total serum lipid levels.
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              Use of agricultural pesticides and prostate cancer risk in the Agricultural Health Study cohort.

              The authors examined the relation between 45 common agricultural pesticides and prostate cancer incidence in a prospective cohort study of 55,332 male pesticide applicators from Iowa and North Carolina with no prior history of prostate cancer. Data were collected by means of self-administered questionnaires completed at enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 1999. A prostate cancer standardized incidence ratio was computed for the cohort. Odds ratios were computed for individual pesticides and for pesticide use patterns identified by means of factor analysis. A prostate cancer standardized incidence ratio of 1.14 (95% confidence interval: 1.05, 1.24) was observed for the Agricultural Health Study cohort. Use of chlorinated pesticides among applicators over 50 years of age and methyl bromide use were significantly associated with prostate cancer risk. Several other pesticides showed a significantly increased risk of prostate cancer among study subjects with a family history of prostate cancer but not among those with no family history. Important family history-pesticide interactions were observed.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                May 2010
                17 December 2009
                : 118
                : 5
                : 659-665
                Affiliations
                Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
                Author notes
                Address correspondence to N. Sawada, Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji Chuo-ku Tokyo 104-0045 Japan. Telephone: 81 3 3542 2511. Fax: 81 3 3547 8578. E-mail: nsawada@ 123456ncc.go.jp

                The authors declare they have no competing financial interests.

                Article
                ehp-118-659
                10.1289/ehp.0901214
                2866682
                20435560
                2c398fe6-ed9a-4911-abda-b36ea08b9f4a
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 17 July 2009
                : 17 December 2009
                Categories
                Research

                Public health
                japanese men,jphc study,prostate cancer,nested case-control study,organochlorines
                Public health
                japanese men, jphc study, prostate cancer, nested case-control study, organochlorines

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