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Effects of 9-cis-Retinoic Acid on the Insulin-Like Growth Factor Axis in Former Smokers

From The University of Texas Graduate School of Biomedical Sciences at Houston and The University of Texas M.D. Anderson Cancer Center, Houston, TX

Address reprint requests to Ho-Young Lee, PhD, Department of Thoracic/Head & Neck Medical Oncology, and the Program in Cancer Biology, Unit 432, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: hlee{at}mdanderson.org

PURPOSE: Insulin-like growth factor (IGF) axis has been associated with the risk of lung cancer. 9-cis-retinoic acid (9-cis-RA) has shown potential chemopreventive activities in former smokers. This study was designed to evaluate the effects of 9-cis-RA on IGF axis in former smokers to identify any benefit the retinoid may have in preventing lung cancer.

PATIENTS AND METHODS: Serum concentrations of IGF-I, IGF binding protein (IGFBP)-3, and their molar ratio (IGF-I/IGFBP-3) were measured with radioimmunoassay kits in stored blood samples from the participants of an original chemoprevention trial. The participants had ceased smoking for at least 12 months and were randomly assigned to receive 3 months of daily oral 9-cis-RA (100 mg) or placebo. All statistical tests were two-sided.

RESULTS: A total of 111 samples from the study's baseline and 84 samples from the 3 months treatment were analyzed. The serum concentrations of IGF-I and IGF-I/IGFBP-3 at baseline were significantly lower in female than in male participants. After 3 months of treatment, the serum level of IGF-I and IGF-I/IGFBP-3 were significantly lower in the 9-cis-RA group than in the placebo group (P = .03 and P < .01, respectively), but the IGFBP-3 level was significantly higher (P = .03).

CONCLUSION: 9-cis-RA treatment modulated the IGF axis in former smokers, suggesting that the IGF axis is a potential target for the chemopreventive activities of 9-cis-RA and that the serum concentrations of IGF, IGFBP-3, and IGF-I/IGFBP-3 could serve as surrogate end point biomarkers of 9-cis-RA treatment.

Supported in part by National Institutes of Health Grants U19 CA68437 (W.K.H.), R01 CA109520-01 (H.-Y.L.), CA-100816-01A1 (H.-Y.L), American Cancer Society grant RSG-04-082-01-TBE 01(H.-Y.L), and W81XWH-04-1-0142-01-VITAL from the Department of Defense (W.K.H.). W.K.H. is an American Cancer Society Clinical Research Professor.

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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