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      Association between dioxin and cancer incidence and mortality: a meta-analysis

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          Abstract

          The objective of the present study was to systematically assess the association between dioxin/2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cancer incidence and mortality. Systematic literature searches were conducted until July 2015 in Pubmed, Embase and Cochrane library to identify relevant studies. A random-effects model was applied to estimate the pooled odds ratio (OR), risk ratio (RR), standard incidence ratio (SIR) or standard mortality ratio (SMR) for cancer incidence or mortality. In addition, dose-response, meta-regression, subgroup, and publication bias analyses were conducted. Thirty-one studies involving 29,605 cancer cases and 3,478,748 participants were included. Higher external exposure level of TCDD was significantly associated with all cancer mortality (pooled SMR = 1.09, 95% CI: 1.01–1.19, p = 0.04), but not all cancer incidence (pooled RR = 1.01, 95% CI: 0.97–1.06, p = 0.49). Higher blood level of TCDD was both significantly associated with all cancer incidence (pooled RR = 1.57, 95% CI: 1.21–2.04, p = 0.001) and all cancer mortality (pooled SMR = 1.45, 95% CI: 1.25–1.69, p < 0.001). Subgroup analysis suggested that higher external exposure and blood level of TCDD were both significantly associated with the mortality caused by non-Hodgkin’s lymphoma. In conclusion, external exposure and blood level of TCDD were both significantly associated with all cancer mortality, especially for non-Hodgkin’s lymphoma.

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          A strategy for modelling the effect of a continuous covariate in medicine and epidemiology.

          P Royston (2000)
          Low-dimensional parametric models are well understood, straightforward to communicate to other workers, have very smooth curves and may easily be checked for consistency with background scientific knowledge or understanding. They should therefore be ideal tools with which to represent smooth relationships between a continuous predictor and an outcome variable in medicine and epidemiology. Unfortunately, a seriously restricted set of such models is used routinely in practical data analysis - typically, linear, quadratic or occasionally cubic polynomials, or sometimes a power or logarithmic transformation of a covariate. Since their flexibility is limited, it is not surprising that the fit of such models is often poor. Royston and Altman's recent work on fractional polynomials has extended the range of available functions. It is clearly crucial that the chosen final model fits the data well. Achieving a good fit with minimal restriction on the functional form has been the motivation behind the major recent research effort on non-parametric curve-fitting techniques. Here I propose that one such model, a (possibly over-fitted) cubic smoothing spline, may be used to define a suitable reference curve against which the fit of a parametric model may be checked. I suggest a significance test for the purpose and examine its type I error and power in a small simulation study. Several families of parametric models, including some with sigmoid curves, are considered. Their suitability in fitting regression relationships found in several real data sets is investigated. With all the example data sets, a simple parametric model can be found which fits the data approximately as well as a cubic smoothing spline, but without the latter's tendency towards artefacts in the fitted curve. Copyright 2000 John Wiley & Sons, Ltd.
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            Health effects of dioxin exposure: a 20-year mortality study.

            Follow-up of the population exposed to dioxin after the 1976 accident in Seveso, Italy, was extended to 1996. During the entire observation period, all-cause and all-cancer mortality did not increase. Fifteen years after the accident, mortality among men in high-exposure zones A (804 inhabitants) and B (5,941 inhabitants) increased from all cancers (rate ratio (RR) = 1.3, 95% confidence interval (CI): 1.0, 1.7), rectal cancer (RR = 2.4, 95% CI: 1.2, 4.6), and lung cancer (RR = 1.3, 95% CI: 1.0, 1.7), with no latency-related pattern for rectal or lung cancer. An excess of lymphohemopoietic neoplasms was found in both genders (RR = 1.7, 95% CI: 1.2, 2.5). Hodgkin's disease risk was elevated in the first 10-year observation period (RR = 4.9, 95% CI: 1.5, 16.4), whereas the highest increase for non-Hodgkin's lymphoma (RR = 2.8, 95% CI: 1.1, 7.0) and myeloid leukemia (RR = 3.8, 95% CI: 1.2, 12.5) occurred after 15 years. No soft tissue sarcoma cases were found in these zones (0.8 expected). An overall increase in diabetes was reported, notably among women (RR = 2.4, 95% CI: 1.2, 4.6). Chronic circulatory and respiratory diseases were moderately increased, suggesting a link with accident-related stressors and chemical exposure. Results support evaluation of dioxin as carcinogenic to humans and corroborate the hypotheses of its association with other health outcomes, including cardiovascular- and endocrine-related effects.
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              Case-control study: soft-tissue sarcomas and exposure to phenoxyacetic acids or chlorophenols.

              In 1977 a number of patients with soft-tissue sarcomas and previous exposure to phenoxyacetic acids were described. Following from these observations a matched case-control study was made. Exposure to chlorophenols was also included in this study. The results showed that exposure to phenoxyacetic acids or chlorophenols gave an approximately 6-fold increase in the risk for this type of tumour. It was not possible to determine, however, whether the carcinogenic effect was exerted by these compounds or by impurities such as chlorinated dibenzodioxins and dibenzofurans that in almost all cases were part of the commercial preparations.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                29 November 2016
                2016
                : 6
                : 38012
                Affiliations
                [1 ]Department of Toxicology, Zhejiang University School of Public Health , Hangzhou, 310058, China
                [2 ]Second Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, 310009, China
                [3 ]Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, 310009, China
                [4 ]Department of Thoracic Surgery, The first Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, 310003, China
                Author notes
                [*]

                These authors contributed equally to this work.

                Article
                srep38012
                10.1038/srep38012
                5126552
                27897234
                fb9dd40a-629e-4139-b139-28f75316f94c
                Copyright © 2016, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 14 February 2016
                : 03 November 2016
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