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      Isoflavone and Soyfood Intake and Colorectal Cancer Risk: A Case-Control Study in Korea

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          Abstract

          We aimed to assess the relationship between dietary soyfood and isoflavone intake and colorectal cancer risk in a case-control study. A total of 901 colorectal cancer cases and 2669 controls were recruited at the National Cancer Center, Korea. A semi-quantitative food frequency questionnaire was used to assess the usual dietary habits, and the isoflavone intake level was estimated from five soyfood items. A high intake of total soy products, legumes, and sprouts was associated with a reduced risk for colorectal cancer in men and women, although the middle quartiles of intake of total soy products were associated with an elevated risk. In contrast, a high intake of fermented soy paste was associated with an elevated risk for colorectal cancer in men. The groups with the highest intake quartiles of isoflavones showed a decreased risk for colorectal cancer compared to their counterparts with the lowest intake quartiles in men (odds ratio (OR): 0.67, 95% confidence interval (CI): 0.51–0.89) and women (OR: 0.65, 95% CI: 0.43–0.99). The reduced risk for the highest intake groups persisted for distal colon cancer in men and rectal cancer in women. The association between soyfood intake and colorectal cancer risk was more prominent among post-menopausal women than pre-menopausal women. In conclusion, a high intake of total soy products or dietary isoflavones was associated with a reduced risk for overall colorectal cancer, and the association may be more relevant to distal colon or rectal cancers.

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          The role of soy products in reducing risk of cancer.

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            Increasing Trend of Colorectal Cancer Incidence in Korea, 1999-2009

            Purpose This study was conducted in order to demonstrate changing trends in colorectal cancer incidence according to sex, age group, and anatomical location in the Korean population. Materials and Methods Data from the Korea Central Cancer Registry between 1999 and 2009 were analyzed. Annual percent changes (APCs) of sex- and age-specific incidence rates for cancer of the proximal colon (International Statistical Classification of Diseases and Related Health Problems, 10th revision [ICD-10] code C18.0-18.5), distal colon (C18.6-18.7), and rectum (C19-20), and male-to-female incidence rate ratios (IRR) were calculated. Results The age-standardized incidence rate (ASR) of colorectal cancer was 27 (per 100,000) in 1999 and increased to 50.2 in 2009 among men (APC, 6.6%). The ASR for women was 17.2 in 1999 and 26.9 in 2009 (APC, 5.1%). The rectum was the most common site of cancer among both men and women during 1999 and 2009. However, the distal colon had the highest APC (10.8% among men and 8.4% among women), followed by the proximal colon (7.9% among men and 6.6% among women), and rectum (5.2% among men and 2.4% among women). The proportion of rectal cancer decreased from 51.5% in 1999 to 47.1% in 2009 among men, and from 50.5% to 42.8% among women. An increase in the male-to-female IRR was observed for distal colon cancer and rectal cancer, whereas the IRR for proximal colon cancer was stable. Conclusion The rapid increase in colorectal cancer incidence is mainly attributed to the increase in colon cancer, especially distal colon cancer, and may be explained by a transition of risk factors for subsites or by the effect of colorectal cancer screening.
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              Isoflavone metabolites and their in vitro dual functions: they can act as an estrogenic agonist or antagonist depending on the estrogen concentration.

              The major soy isoflavones are daidzin and genistin, the glycoside conjugates of daidzein (DZ) and genistein (GTN). After ingestion, they are metabolized into diverse compounds in the gut. The marked inter-individual variation has been suggested in their metabolism. The clinical effects may be modulated by the metabolic ability to produce a more potent metabolite than the precursor. Our study was, therefore, designed to analyze and compare in vitro biologic activities of their metabolites: DZ, GTN, dihydrogenistein (DGTN), dihydrodaidzein (DDZ), tetrahydrodaidzein (TDZ), O-desmethylangolensin (ODMA), and equol (EQL). Furthermore, we investigated their modulatory effects in the presence of estrogen using several in vitro systems. The intermediate metabolites, such as DGTN, DDZ, and TDZ, bind much weakly to both ERs and induce less potently in transcriptional activity, gene expression, and mammary cell proliferation than their precursors. EQL has the strongest binding affinities and estrogenic activities especially for ERbeta among the daidzin metabolites and shows the ability to suppress osteoclast formation at high doses. The test isoflavonoids act like estrogen antagonists with the premenopausal dose of E2 and thus inhibit estrogenic actions by E2, whereas they exert estrogen agonist activity with the lower dose of estrogen close to the serum levels of postmenopausal women. Our results suggest that phytoestrogens such as isoflavones may exert their effects as estrogen antagonists in a high estrogen environment, or they may act as estrogen agonists in a low estrogen environment.
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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, CA USA )
                1932-6203
                17 November 2015
                2015
                : 10
                : 11
                : e0143228
                Affiliations
                [1 ]Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, 110–799, Republic of Korea
                [2 ]Molecular Epidemiology Branch, National Cancer Center, Goyang-si, 410–769, Republic of Korea
                [3 ]Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 120–750, Republic of Korea
                [4 ]Gachon University College of Nursing, Incheon, 406–799, Republic of Korea
                [5 ]Department of Surgery, Seoul National University College of Medicine and Hospital, Seoul, 110–799, Republic of Korea
                [6 ]Center for Colorectal Cancer, National Cancer Center, Goyang-si, 410–769, Republic of Korea
                Baylor University Medical Center, UNITED STATES
                Author notes

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

                Conceived and designed the experiments: AS JHO JK. Performed the experiments: JL JWP SCP JHO. Analyzed the data: JHL JL. Wrote the paper: AS MSP.

                Article
                PONE-D-15-34365
                10.1371/journal.pone.0143228
                4648565
                26575841
                db8a730f-32f5-4a61-9ecc-cc4aa5dbabe6
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 5 August 2015
                : 2 November 2015
                Page count
                Figures: 0, Tables: 5, Pages: 17
                Funding
                The research relating to this abstract was funded by the National Research Foundation of Korea (2010-0010276, 2013R1A1A2A10008260) and the National Cancer Center, Korea (0910220, 1210141).
                Categories
                Research Article
                Custom metadata
                All relevant data such as numbers behind statistical measures and the frequency of subjects in each categories are within the paper. Those who would like to access to additional data which were used for the analysis may contact jskim@ 123456ncc.re.kr .

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