Insulin-like growth factor-I concentration and risk of prostate cancer: results from the European Prospective Investigation into Cancer and Nutrition.
Price AJ., Allen NE., Appleby PN., Crowe FL., Travis RC., Tipper SJ., Overvad K., Grønbæk H., Tjønneland A., Johnsen NF., Rinaldi S., Kaaks R., Lukanova A., Boeing H., Aleksandrova K., Trichopoulou A., Trichopoulos D., Andarakis G., Palli D., Krogh V., Tumino R., Sacerdote C., Bueno-de-Mesquita HB., Argüelles MV., Sánchez MJ., Chirlaque MD., Barricarte A., Larrañaga N., González CA., Stattin P., Johansson M., Khaw KT., Wareham N., Gunter M., Riboli E., Key T.
BACKGROUND: High circulating insulin-like growth factor-I (IGF-I) concentrations have been associated with increased risk for prostate cancer in several prospective epidemiological studies. In this study, we investigate the association between circulating IGF-I concentration and risk of prostate cancer over the long term in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: In a nested case-control design, 1,542 incident prostate cancer cases from eight European countries were individually matched to 1,542 controls by study center, age at recruitment, duration of follow-up, time of day, and duration of fasting at blood collection. Conditional logistic regression models were used to calculate risk for prostate cancer associated with IGF-I concentration, overall and by various subgroups. RESULTS: Circulating IGF-I concentration was associated with a significant increased risk for prostate cancer [OR for highest vs. lowest quartile, 1.69; 95% confidence interval (CI), 1.35-2.13; P(trend) = 0.0002]. This positive association did not differ according to duration of follow-up [ORs for highest vs. lowest quartile were 2.01 (1.35-2.99), 1.37 (0.94-2.00), and 1.80 (1.17-2.77) for cancers diagnosed <4, 4-7, and >7 years after blood collection, respectively (P(heterogeneity) = 0.77)] or by stage, grade, and age at diagnosis or age at blood collection (all subgroups P(heterogeneity) >0.05). CONCLUSION: In this European population, high circulating IGF-I concentration is positively associated with risk for prostate cancer over the short and long term. IMPACT: As IGF-I is the only potentially modifiable risk factor so far identified, research into the effects of reducing circulating IGF-I levels on subsequent prostate cancer risk is warranted.