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      Is there a role for IGF‐1 in the development of second primary cancers?

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          Abstract

          Cancer survival rates are increasing, and as a result, more cancer survivors are exposed to the risk of developing a second primary cancer ( SPC). It has been hypothesized that one of the underlying mechanisms for this risk could be mediated by variations in insulin‐like growth factor‐1 ( IGF‐1). This review summarizes the current epidemiological evidence to identify whether IGF‐1 plays a role in the development of SPCs. IGF‐1 is known to promote cancer development by inhibiting apoptosis and stimulating cell proliferation. Epidemiological studies have reported a positive association between circulating IGF‐1 levels and various primary cancers, such as breast, colorectal, and prostate cancer. The role of IGF‐1 in increasing SPC risk has been explored less. Nonetheless, several experimental studies have observed a deregulation of the IGF‐1 pathway, which may explain the association between IGF‐1 and SPCs. Thus, measuring serum IGF‐1 may serve as a useful marker in assessing the risk of SPCs, and therefore, more translational experimental and epidemiological studies are needed to further disentangle the role of IGF‐1 in the development of specific SPCs.

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          Most cited references96

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          Insulin-like growth factors and neoplasia.

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            Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study.

            Insulin-like growth factor-I (IGF-I) is a mitogen for prostate epithelial cells. To investigate associations between plasma IGF levels and prostate cancer risk, a nested case-control study within the Physicians' Health Study was conducted on prospectively collected plasma from 152 cases and 152 controls. A strong positive association was observed between IGF-I levels and prostate cancer risk. Men in the highest quartile of IGF-I levels had a relative risk of 4.3 (95 percent confidence interval 1.8 to 10.6) compared with men in the lowest quartile. This association was independent of baseline prostate-specific antigen levels. Identification of plasma IGF-I as a predictor of prostate cancer risk may have implications for risk reduction and treatment.
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              Role of the insulin-like growth factor family in cancer development and progression.

              H Yu, T. Rohan (2000)
              The insulin-like growth factors (IGFs) are mitogens that play a pivotal role in regulating cell proliferation, differentiation, and apoptosis. The effects of IGFs are mediated through the IGF-I receptor, which is also involved in cell transformation induced by tumor virus proteins and oncogene products. Six IGF-binding proteins (IGFBPs) can inhibit or enhance the actions of IGFs. These opposing effects are determined by the structures of the binding proteins. The effects of IGFBPs on IGFs are regulated in part by IGFBP proteases. Laboratory studies have shown that IGFs exert strong mitogenic and antiapoptotic actions on various cancer cells. IGFs also act synergistically with other mitogenic growth factors and steroids and antagonize the effect of antiproliferative molecules on cancer growth. The role of IGFs in cancer is supported by epidemiologic studies, which have found that high levels of circulating IGF-I and low levels of IGFBP-3 are associated with increased risk of several common cancers, including those of the prostate, breast, colorectum, and lung. Evidence further suggests that certain lifestyles, such as one involving a high-energy diet, may increase IGF-I levels, a finding that is supported by animal experiments indicating that IGFs may abolish the inhibitory effect of energy restriction on cancer growth. Further investigation of the role of IGFs in linking high energy intake, increased cell proliferation, suppression of apoptosis, and increased cancer risk may provide new insights into the etiology of cancer and lead to new strategies for cancer prevention.
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                Author and article information

                Contributors
                thurkaa.t.shanmugalingam@kcl.ac.uk
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                13 October 2016
                November 2016
                : 5
                : 11 ( doiID: 10.1002/cam4.2016.5.issue-11 )
                : 3353-3367
                Affiliations
                [ 1 ] Division of Cancer StudiesCancer Epidemiology Group King's College London LondonUnited Kingdom
                [ 2 ] Randall Division of Cell and Molecular BiophysicsKing's College London LondonUnited Kingdom
                Author notes
                [*] [* ] Correspondence

                Thurkaa Shanmugalingam, Division of Cancer Studies, Cancer Epidemiology Group, Research Oncology, King's College London, 3rd Floor, Bermondsey Wing, Guy's Hospital, London SE1 9RT, United Kingdom. Tel: +44 0 20 7188 7904; Fax: +44 0 20 7188 9986; E‐mail: thurkaa.t.shanmugalingam@ 123456kcl.ac.uk

                Article
                CAM4871
                10.1002/cam4.871
                5119990
                27734632
                c5d21b1a-d9b9-4adc-9376-2ee7b479a78f
                © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 October 2015
                : 08 June 2016
                : 24 June 2016
                Page count
                Figures: 2, Tables: 1, Pages: 18, Words: 10678
                Funding
                Funded by: Experimental Cancer Medicine Centre at King's College London
                Funded by: Cancer Research UK (AJR)
                Funded by: National Institute for Health Research (NIHR)
                Funded by: Biomedical Research Centre
                Funded by: NHS Foundation Trust
                Funded by: King's College London
                Categories
                Review
                Cancer Prevention
                Review
                Custom metadata
                2.0
                cam4871
                November 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.8 mode:remove_FC converted:22.11.2016

                Oncology & Radiotherapy
                breast cancer,colorectal cancer,igf‐1,lung cancer,prostate cancer,second primary cancer

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