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      Circulating Thyroxine, Thyroid-Stimulating Hormone, and Hypothyroid Status and the Risk of Prostate Cancer

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          Abstract

          Background

          Thyroid hormones may influence risk of cancer through their role in cell differentiation, growth, and metabolism. One study of circulating thyroid hormones supports this hypothesis with respect to prostate cancer. We undertook a prospective analysis of thyroid hormones and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

          Methods

          Within the ATBC Study, a randomized controlled trial of α-tocopherol and β-carotene supplements and cancer incidence in male smokers, 402 prostate cancer cases were sampled. Controls were matched 2∶1 to cases on age and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer were estimated for quintiles of serum total and free thyroxine (T4), thyroid-stimulating hormone (TSH), thyroid-binding globulin (TBG), and by categories of thyroid status.

          Results

          Men with serum higher TSH had a decreased risk of prostate cancer compared to men with lower TSH (Q5 vs. Q1–4: OR = 0.70, 95% CI: 0.51–0.97, p = 0.03). When the T4 and TSH measurements were combined to define men as hypothyroid, euthyroid or hyperthyroid, hypothyroid men had a lower risk of prostate cancer compared to euthyroid men (OR = 0.48, 95% CI = 0.28–0.81, p = 0.006). We observed no association between hyperthyroid status and risk, although the number of hyperthyroid men with prostate cancer was small (n = 9).

          Conclusions

          In this prospective study of smokers, men with elevated TSH and those classified as being in a hypothyroid state were at decreased risk of prostate cancer. Future studies should examine the association in other populations, particularly non-smokers and other racial/ethnic groups.

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          Most cited references19

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          Physiological and molecular basis of thyroid hormone action.

          P M Yen (2001)
          Thyroid hormones (THs) play critical roles in the differentiation, growth, metabolism, and physiological function of virtually all tissues. TH binds to receptors that are ligand-regulatable transcription factors belonging to the nuclear hormone receptor superfamily. Tremendous progress has been made recently in our understanding of the molecular mechanisms that underlie TH action. In this review, we present the major advances in our knowledge of the molecular mechanisms of TH action and their implications for TH action in specific tissues, resistance to thyroid hormone syndrome, and genetically engineered mouse models.
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            Thyroid function and cancer risk: a prospective population study.

            It has been hypothesized that thyroid function may influence cancer risk, but few studies with adequate statistical power have investigated this question, and the results have not been consistent. In a prospective study of 29,691 people (19,710 women and 9,981 men) without previously known thyroid disease, thyrotropin was measured at baseline, and cancer incidence was recorded during 9 years of follow-up. Using Cox regression analysis, we studied the associations (hazard ratios) of thyrotropin categories with total cancer risk, and specifically, with risk of lung, colon, prostate, and breast cancer adjusted for age, sex, and smoking status. Low thyrotropin levels (<0.50 mU/L) were associated with increased cancer risk [adjusted hazard ratio (HR), 1.34; 95% confidence interval (CI), 1.06-1.69] compared with the euthyroid reference group. The higher risk was driven by lung cancer (adjusted HR, 2.34; 95% CI, 1.24-4.40) and prostate cancer (adjusted HR, 1.97; 95% CI, 1.04-3.76). After excluding the first 2 years of follow-up, the associations were strengthened to 2.91 (1.49-5.70) for lung cancer and 2.60 (1.36-4.99) for prostate cancer. Thyrotropin levels suggestive of hyperthyroid function are associated with increased cancer risk, and specifically, with increased risk of lung and prostate cancer, whereas hypothyroid function does not seem to be associated with cancer risk.
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              The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. The ATBC Cancer Prevention Study Group.

              The Alpha-Tocopherol, Beta-Carotene (ATBC) Lung Cancer Prevention Study was a randomized, double-blind, placebo-controlled, 2 x 2 factorial design, primary prevention trial testing the hypothesis that alpha-tocopherol (50 mg/day) and beta-carotene (20 mg/day) supplements reduce the incidence of lung cancer and possibly other cancers. Total and disease-specific mortality and incidence of various diseases and symptoms were monitored for safety. Between 1985 and 1993, 29,133 eligible male smokers aged 50 to 69 years at entry were randomized to receive daily active supplements or placebo capsules for 5 to 8 years (median 6.1 years), accumulating 169,751 follow-up years. This report describes the study design, methods, and protocol as well as the baseline characteristics and capsule compliance of the participants. The ATBC Study is the largest lung cancer chemoprevention trial conducted to date.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                30 October 2012
                : 7
                : 10
                : e47730
                Affiliations
                [1 ]Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Department of Health and Human Services, Bethesda, Maryland, United States of America
                [2 ]Laboratory Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America
                [3 ]Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
                National University of Ireland Galway, Ireland
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: DA JV AMM. Performed the experiments: ATR TB. Analyzed the data: AMM. Contributed reagents/materials/analysis tools: ATR. Wrote the paper: AMM SJW DA.

                Article
                PONE-D-12-19173
                10.1371/journal.pone.0047730
                3484141
                23118893
                0696762d-4c67-4e19-8069-5d3e1e00ff17
                Copyright @ 2012

                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 3 July 2012
                : 14 September 2012
                Page count
                Pages: 7
                Funding
                This work was was supported by the United States Public Health Service (contract numbers N01-CN-45165, N01-RC-45035, N01-RC-37004, and HHSN261201000006C) from the National Cancer Institute, Department of Health and Human Services, and by funding from the Intramural Research Program of the National Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Diagnostic Medicine
                Pathology
                General Pathology
                Biomarkers
                Epidemiology
                Oncology
                Cancer Risk Factors
                Hormonal Causes of Cancer
                Cancers and Neoplasms
                Genitourinary Tract Tumors
                Prostate Cancer

                Uncategorized
                Uncategorized

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