Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC).
Peeters PHM., Lukanova A., Allen N., Berrino F., Key T., Dossus L., Rinaldi S., van Gils CH., Bueno-de-Mesquita HB., Boeing H., Schulz M., Chang-Claude J., Linseisen J., Panico S., Sacerdote C., Palli D., Tumino R., Trichopoulou A., Trichopolos D., Bamia C., Larranaga N., Ardanaz E., Pera G., Quirós JR., Martínez-García C., Navarro C., Bingham SA., Khaw K-T., Clavel F., Tjonneland A., Olsen A., Overvad K., Tetsche MS., Lund E., Lundin E., Berglund G., Riboli E., Kaaks R.
We set out to study the relationship between circulating levels of IGF-I and its major binding protein (IGFBP-3) in relation to ovarian cancer risk. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of IGF-I and IGFBP-3 were measured in prediagnostic serum samples of 214 women who subsequently developed ovarian cancer, and 388 matched control subjects. Conditional logistic regression models were used to estimate relative risks of ovarian cancer by tertiles of IGF-I and IGFBP-3 levels. For all women, there was no association between the circulating IGF-I or IGFBP-3 levels and the risk of ovarian cancer. However, among women diagnosed with ovarian cancer aged 55 or younger, the relative risk was higher in the middle or top tertiles of serum IGF-I, when compared with women in the lowest tertile (odds ratios (OR) = 1.8 (95%CI 0.7-4.3) and OR = 2.4 (95%CI 0.9-6.4); P(trend) = 0.08) respectively. These results were adjusted for body mass index, previous hormone use, fertility problems, and parity. Restricting the analysis to women who were premenopausal at blood donation, relative risks for ovarian cancer diagnosed before age 55 were higher (OR = 5.1 (95%CI 1.5-18.2) and OR = 5.6 (95%CI 1.5-20.8) respectively, for second and third tertiles; P(trend) = 0.02). Adjustment for serum IGFBP-3 levels only slightly attenuated relative risk estimates. Relations between IGFBP-3 and ovarian cancer before age 55 were in the same direction as for IGF-I, but less strong and statistically not significant. In women aged over 55, there was no association between serum IGF-I or IGFBP-3 and ovarian cancer risk. Our results suggest that the circulating levels of IGF-I may play a potentially important role in the development of ovarian cancer in women of a pre- or perimenopausal age.