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Title: Higher Circulating Concentrations of Insulin-Like Growth Factor-1 and Main Binding Protein Appear Associated with Increased Risk of Common Cancers

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Lancet 2004;363:1346-1336.
04/23/2004 10:04:00 AM
By Joene Hendry

Higher concentrations of circulating total insulin-like growth factor (IGF)-1 appear associated with an increased risk of prostate and premenopausal breast cancers, while higher concentrations of IGF binding protein (IGFBP)-3 appear associated with premenopausal breast cancer. "The dose-response analysis showed that increasing IGF-1 concentrations were associated with an increased risk of prostate cancer and premenopausal breast cancer," writes Andrew G. Renehan, PhD, Department of Surgery, Christie Hospital NHS Trust, Manchester, United Kingdom, and colleagues. "IGFBP-3 concentrations were also associated with an increased risk of premenopausal breast cancer, but not with any other cancer," they add. The investigators conducted a systematic review and meta-regression analysis of studies assessing the association between serum and plasma concentrations of IGF-1 and IGFBP-3 and prostate, colorectal, and pre- and postmenopausal breast cancers. All of the 21 studies, 15 prospective and 6 case-control, that met inclusion criteria were published in English from 1998 onward, and included 3609 cases and 7137 controls. Overall, 6 studies investigated prostate cancer, while 5, 6, and 4 investigated colorectal, breast, and lung cancers, respectively. While higher concentrations of IGF-1 were associated with prostate, colorectal, and premenopausal breast cancer, modelling of the dose-response relationship between blood concentrations and cancer risk confirmed the associations for prostate cancer and premenopausal breast cancer, but not for colorectal cancer. The odds ratios of patients in the 75th percentile compared with the 25th percentile of IGF-1 concentrations were 1.49 for prostate cancer, and 1.65 for premenopausal breast cancer, compared with 1.18 for colorectal cancer, 1.01 for lung cancer, and 0.95 for postmenopausal breast cancer. Similar analysis of patients in the 75th percentile compared with the 25th percentile of IGFBP-3 concentrations were 1.51 for premenopausal breast cancer, compared with 0.95 for prostate cancer, 1.16 for colorectal cancer, 1.01 for postmenopausal breast cancer, and 0.98 for lung cancer. "Our findings suggest that circulating IGF-1 and IGFBP-3 have a role in cancer risk assessment and prevention," the authors conclude. "Taken together, cancers of the prostate, colorectal, breast, and lung account for more than 2 million new cases in developed countries every year," the authors note, adding "The elevated concentrations of IGF's might thus contribute greatly to the burden of cancer in these populations."

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