Circulating
insulin-like growth factors (IGFs) and their
binding proteins have been associated with increased risk of breast, prostate, colon, and
lung cancer. To examine the association of IGFs and
endometrial cancer risk, we measured the plasma levels of
IGF-1,
IGF-2, and
IGF binding protein 3 (IGFBP-3) by ELISA in 80 women with
endometrial cancer and 80 age-matched control subjects with no history of
cancer. Mean plasma levels of
IGF-2 were significantly higher in women with
cancer versus controls (670 ng/ml versus 380 ng/ml, P < 0.001). In contrast, significantly lower mean plasma levels of
IGF-1 (155 mg/ml versus 185 ng/ml, P < 0.01) and
IGFBP-3 (1703 ng/ml versus 2170 ng/ml, P < 0.001) were observed among cases compared to the control group. Women in the highest quartile of
IGF-2 were found to have 9.67 (95% confidence interval 3.29-28.43) times the risk of
endometrial cancer than women in the lowest quartiles. Women in the highest quartile of
IGFBP-3 were associated with a significantly decreased risk for developing
endometrial cancer (odds ratio = 0.23, 95% confidence interval 0.09-0.60). These data suggest that increased plasma levels of
IGF-2 and decreased levels of
IGFBP-3 are associated with an increased risk of
endometrial cancer. Further validation of these results is needed to determine the potential usefulness of risk assessment.