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Serum Levels of Insulin-like Growth Factor I and Risk of Squamous Intraepithelial Lesions of the Cervix¹

Departments of Epidemiology [X. W., H. Z., M. R. S.], Gynecologic Oncology [G. T-L., M. F.], and Biomedical Engineering Center [D. P., M. F.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Squamous intraepithelial lesions (SILs) are areas of precancerous growth in the cervix that can be indicative of future cervical cancer. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have been implicated in cancer development. Recent studies have demonstrated that elevated plasma IGF-I levels are associated with increased risk of prostate, lung, colon, and breast cancers. In this case-control study, we analyzed the relationship between serum levels of IGF-I and IGFBP-3, and SILs of the cervix. The case patients were comprised of 267 women treated at The University of Texas M. D. Anderson Cancer Center Colposcopy Clinic in Houston, Texas for abnormal Pap smears. The clinic serves minority and economically disadvantaged women referred from the County Health Department clinics of Harris County, Texas. The control subjects were 238 healthy women receiving family planning and screening services at two Harris County Health Department clinics. Case patients with either high-grade or low-grade SILs had significantly higher serum levels of IGF-I, IGFBP-3, and molar ratios of IGF-I:IGFBP-3 than the control subjects did. IGF-I levels in the highest quartile were associated with significantly higher risk of SILs compared with the lowest quartile, independent of IGFBP-3 levels. The odds ratio for the fourth quartile of IGF-I level, relative to the first quartile, was 8.54 (95% confidence interval, 4.15–17.60; P < 0.0001) after adjustment for age, ethnicity, smoking status, and IGFBP-3 level. There was a dose-response relationship between risk of SILs and the level of IGF-I: as the level of IGF-I increased, so did the risk of SILs. In addition, the serum level of IGFBP-3 was significantly higher in case patients than in control subjects. However, after adjustment for IGF-I, no relationship was evident between IGFBP-3 level and risk of SILs. Serum levels of IGF-I may be a useful biomarker for assessing risk of SIL development.

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