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Number of aberrant crypt foci associated with adiposity and IGF1 bioavailability

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Abstract

Background

Dysregulation of the insulin-like growth factor (IGF) system, a common consequence of adiposity-induced insulin resistance, may be a key underlying mechanism linking excess body weight with colon cancer. Evidence has been derived from studies of cancer and polyps. Supporting data about aberrant crypt foci (ACF), putative pre-polyp changes, have been generated only from animal studies to date.

Methods

We randomly selected 26 patients with sex-specific elevated waist-hip-ratio (WHR) and 26 with normal values from a series of 150 patients seeking routine colonoscopy at the University of Connecticut Health Center. Cross-sectional analyses were performed of ACF number (<5, ≥5) in relation to total IGF1, IGF-binding protein-3 (IGFBP3), insulin, body mass index (BMI), WHR and waist circumference (WC). Visualized ACF in the 20 cm of the distal colon were counted using advanced endoscopic imaging.

Results

Patients with ≥5 ACF had higher BMI, WHR, and WC compared with patients with >5 ACF (p = 0.04, p = 0.03, and p = 0.01, respectively). IGFBP3 was reduced (p = 0.02) and IGF1:IGFBP3 molar ratio was greater (p = 0.03) in patients with ≥5 ACF. We did not observe significant associations between ACF number and insulin or total IGF1.

Conclusions

Our study provides the first report in humans of a possible association of ACF prevalence and IGF1 bioavailability as characterized by IGF1:IGFBP3 molar ratio and IGFBP3 level. More research is needed to determine whether this relationship is varied by ACF features (e.g., size, dysplasia, molecular changes), synchronous cancer and polyps, and is modified by colon cancer risk factors.

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Acknowledgments

We gratefully acknowledge the efforts of Melissa Parente, Lynn Truesdale, and Judy Conway for patient recruitment, data collection, and very valuable information resources. We are thankful to the University of Connecticut General Clinical Research Center (NIH Grant M01 RR06192) for performing ELISAs, and, the Ray and Carole Neag Comprehensive Cancer Center at the University of Connecticut Health Center for infrastructural research support.

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Authors and Affiliations

  1. Colon Cancer Prevention Program, Neag Comprehensive Cancer Center, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030-6325, USA

    Helen Swede, Joseph C. Anderson, Richard G. Stevens, Joel Levine, Bruce M. Brenner, Valerie B. Duffy, Devon C. Pleau & Daniel W. Rosenberg

  2. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, 10461, USA

    Thomas E. Rohan

  3. Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT, 06520, USA

    Herbert Yu

  4. Global Pharmacovigilance and Epidemiology, Bristol-Myers Squibb, Wallingford, CT, 06492, USA

    Jane Brokaw

  5. Division of Endocrinology and Metabolism, University of Connecticut Health Center, Farmington, CT, 06030, USA

    Carl D. Malchoff

  6. Department of Allied Health Sciences, University of Connecticut, Storrs, CT, 06269, USA

    Valerie B. Duffy

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  1. Helen Swede
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  2. Thomas E. Rohan
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Correspondence to Helen Swede.

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Swede, H., Rohan, T.E., Yu, H. et al. Number of aberrant crypt foci associated with adiposity and IGF1 bioavailability. Cancer Causes Control 20, 653–661 (2009). https://doi.org/10.1007/s10552-008-9278-7

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