Obesity, Iron Regulation, and Colorectal Cancer Risk

Goal

In this study we explore whether iron metabolism dysfunction is a mechanism linking obesity to increased risk for colorectal cancer. Dietary iron represents a potential modifiable risk factor that may reduce the overall cancer burden in persons with obesity.

Abstract

This is a career development award to explore the mechanisms and complex interactions through which obesity, inflammation, diet, and nutrient metabolism alter susceptibility to intestinal cancer. The grant supports Dr. Tussing-Humphries’s training in molecular epidemiology, cancer biology and microbiology. In this work, she is mentored by Marian Fitzgibbon, PhD, primarily, as well as by H. Rex Gaskins, PhD, professor of nutritional sciences at the Unversity of Illinois at Urbana-Champaign, and Xavier Llor, MD, PhD, associate professor of medicine at the University of Illinois at Chicago. 

Background: Obesity is an independent risk factor for colorectal colorectal (CRC) although the underlying mechanisms have not been elucidated. Dietary nutrients play a key role in both the prevention and promotion of CRC. While iron is an essential nutrient, excess iron is associated with carcinogenesis. Unlike the systemic compartment, the intestinal lumen lacks an efficient system to regulate iron. In diseases which dietary iron malabsorption and intestinal inflammation co-exist, greater luminal iron is associated with increased intestinal inflammation and a shift of the gut microbiota to more pre-inflammatory strains. However, in such individuals, treatments designed to reduce luminal iron, including diet restriction and chelation, are associated with lower intestinal inflammation and the colonization of protective gut microbes. Obesity, more so in women, is associated with inflammation-induced, hepcidin-medicated, iron metabolism dysfunction characterized by iron deficiency and dietary iron malabsorption. Obesity is also linked to intestinal inflammation. Currently, there is a fundamental gap in understanding how altered iron metabolism impacts CRC risk in obesity.

Specific aims:

  1. Characterize and compare systemic iron status and hepcidin, fecal iron concentrations, colonic inflammation, and guy mircobiota composition and test for relationships among these indices in obese and lean women
  2. Design and conduct a pilot randomized six-week feeding trial to explore the separate effects of two diets designed to decrease luminal iron versus a control diet on systemic inflammation, iron status, and hepcidin; fecal iron concentration; colonic inflammation; and gut microbiota composition in obese women.

Design: A cross-sectional and prospective design will be utilized. The cross-sectional study will enroll anthropometrics, body composition, venous blood draw, and surveys will be completed. Following, participants will collect a fecal sample at home and complete a dietary recall corresponding to the 3 days prior to fecal collection. For the prospective feeding trial, the 40 obese women from the cross-sectional study will be randomized to one of the three six-week diets. During week 6 of the feeding trial, participants will be asked to collect another fecal sample and complete a corresponding dietary recall. Post-trial, the obese women will attend a study visit at which anthropometrics, body composition, venous blood draw, and surveys will be completed.

Principal investigator
Funding Agency

American Cancer Society (Grant No. MRSG 14-025-01 CNE)    

Start date
07/01/2014
End date
06/30/2019
Total award
$683,000
About this grant

Dr. Tussing-Humphries is supported by an American Cancer Society Mentored Research Scholar Grant. 

Related publications


Springfield S, Odoms-Young A, Tussing-Humphreys L, Freels S, Stolley M. Adherence to American Cancer Society and American Institute of Cancer Research dietary guidelines in overweight African American breast cancer survivors. J Cancer Surviv. 2019;13(2):257–268. doi:10.1007/s11764-019-00748-y

Mears M, Tussing-Humphreys L, Cerwinske L, et al. Associations between Alternate Healthy Eating Index-2010, Body Composition, Osteoarthritis Severity, and Interleukin-6 in Older Overweight and Obese African American Females with Self-Reported Osteoarthritis. Nutrients. 2018;11(1):26. Published 2018 Dec 22. doi:10.3390/nu11010026

Yazici C, Wolf PG, Kim H, et al. Race-dependent association of sulfidogenic bacteria with colorectal cancer. Gut. 2017;66(11):1983–1994. doi:10.1136/gutjnl-2016-313321.

Buscemi J, Miguel YS, Tussing-Humphreys L, et al. Rationale and design of Mi-CARE: The mile square colorectal cancer screening, awareness and referral and education project. Contemp Clin Trials. 2017;52:75–79. doi:10.1016/j.cct.2016.11.009.

Pusatcioglu CK, Nemeth E, Fantuzzi G, et al. Systemic and tumor level iron regulation in men with colorectal cancer: a case control study. Nutr Metab (Lond). 2014;11:21. Published 2014 May 13. doi:10.1186/1743-7075-11-21.

News releases


Iron May Be Key Link Between Obesity and Colon Cancer by Elizabeth Mendes for the American Cancer Society (March 4, 2015)