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      Insulin-like growth factors and cancer: no role in screening. Evidence from the BUPA study and meta-analysis of prospective epidemiological studies

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          Abstract

          Insulin-like growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), and insulin-like growth factor binding protein-3 (IGFBP-3) were measured in frozen serum samples from 1051 men with cancer and 3142 controls in a nested case–control study from the British United Provident Association (BUPA) study cohort and associations with 14 cancers were examined, including prostate, colorectal, and lung. A meta-analysis of studies on these three cancer sites was also conducted. In the meta-analysis the odds ratio between the highest quartile IGF-1 group and the lowest quartile group was 1.31 (95% confidence interval (CI): 1.03–1.67) for prostate, 1.37 (1.05–1.78) for colorectal and 1.02 (0.80–1.31) for lung cancer, and for IGF-2 it was 0.72 (0.36–1.44) for prostate and 1.95 (1.26–3.00) for colorectal cancer. Results from the BUPA study were consistent with the estimates from the other studies. There were no statistically significant associations with IGFBP-3 and any of the cancer sites considered. Our results suggest that IGF-1, IGF-2, and IGFBP-3 measurements have no value in cancer screening, although IGF-1 and IGF-2 may be of aetiological significance in relation to colorectal and prostate cancer.

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          Most cited references21

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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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            Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women.

            Leading a Western lifestyle, being overweight, and being sedentary are associated with an increased risk of colorectal cancer. Recent theories propose that the effects of these risk factors may be mediated by increases in circulating insulin levels and in the bioactivity of insulin-like growth factor (IGF)-I. To test this hypothesis, we conducted a case-control study nested within a cohort of 14 275 women in New York. We used blood samples that had been obtained from these women from March 1985 through June 1991 and stored in a biorepository. C-peptide (a marker for insulin secretion), IGF-I, and IGF-binding proteins (IGFBPs)-1, -2, and -3 were assayed in the serum of 102 women who subsequently developed colorectal cancer and 200 matched control subjects. Logistic regression was used to relate cancer risk to these peptide levels, by adjustment for other risk factors. All statistical tests used are two-sided. Colorectal cancer risk increased with increasing levels of C-peptide (P:(trend) =.001), up to an odds ratio (OR) of 2. 92 (95% confidence interval [CI] = 1.26-6.75) for the highest versus the lowest quintiles, after adjustment for smoking. For colon cancer alone (75 case subjects and 146 control subjects), ORs increased up to 3.96 (95% CI = 1.49-10.50; P:(trend) <.001) for the highest versus the lowest quintiles. A statistically significant decrease in colorectal cancer risk was observed for increasing levels of IGFBP-1 (P:(trend) =.02; OR in the upper quintile = 0.48 [95% CI = 0.23-1. 00]), as well as for the highest quintile of IGFBP-2 levels (P:(trend) =.06; OR = 0.38 [95% CI = 0.15-0.94]). Colorectal cancer risk showed a modest but statistically nonsignificant positive association with levels of IGF-I and was statistically significantly increased for the highest quintile of IGFBP-3 (OR = 2.46 [95% CI = 1. 09-5.57]). Chronically high levels of circulating insulin and IGFs associated with a Western lifestyle may increase colorectal cancer risk, possibly by decreasing IGFBP-1 and increasing the bioactivity of IGF-I.
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              When can a risk factor be used as a worthwhile screening test?

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                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                0007-0920
                1532-1827
                27 June 2006
                03 July 2006
                : 95
                : 1
                : 112-117
                Affiliations
                [1 ]Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Barts and The London Queen Mary's School of Medicine and Dentistry , Charterhouse Square, London EC1M 6BQ, UK
                Author notes
                [* ]Author for correspondence: j.k.morris@ 123456qmul.ac.uk
                Article
                6603200
                10.1038/sj.bjc.6603200
                2360494
                16804529
                d20dd8d1-9440-4eb7-8840-7a93d90532d9
                Copyright 2006, Cancer Research UK
                History
                : 24 February 2006
                : 02 May 2006
                : 05 May 2006
                Categories
                Epidemiology

                Oncology & Radiotherapy
                cancer screening,insulin-like growth factors,cohort studies,epidemiology,meta-analysis

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