Su Yon Jung1, Wendy E Barrington, Dorothy S Lane, Chu Chen, Rowan Chlebowski, Giselle Corbie-Smith, Lifang Hou, Zuo-Feng Zhang, Min-So Paek, Carolyn J Crandall. 1. 1Translational Sciences Section, Jonsson Comprehensive Cancer Center, School of Nursing, University of California, Los Angeles, Los Angeles, CA 2Psychosocial & Community Health, School of Nursing, University of Washington, Seattle, WA 3Department of Family, Population and Preventive Medicine, Stony Brook University School of Medicine, Stony Brook, NY 4Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 5Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 6Department of Medicine, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 7Department of Preventive Medicine & Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University Chicago, IL 8Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA 9Department of Social Welfare, Konkuk University, Chungju, South Korea 10Division of General Internal Medicine, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
Abstract
OBJECTIVE: Bioavailable insulin-like growth factor-I (IGF-I) interacts with obesity and exogenous estrogen (E) in a racial disparity in obesity-related cancer risk, yet their interconnected pathways are not fully characterized. We investigated whether circulating bioavailable IGF-I acted as a mediator of the racial disparity in obesity-related cancers such as breast and colorectal (CR) cancers and how obesity and E use regulate this relationship. METHODS: A total of 2,425 white and 164 African American (AA) postmenopausal women from the Women's Health Initiative Observational Study were followed from October 1, 1993 through August 29, 2014. To assess bioactive IGF-I as a mediator of race-cancer relationship, we used the Baron-Kenny method and quantitative estimation of the mediation effect. RESULTS: Compared with white women, AA women had higher IGF-I levels; their higher risk of CR cancer, after accounting for IGF-I, was no longer significant. IGF-I was associated with breast and CR cancers even after controlling for race. Among viscerally obese (waist/hip ratio >0.85) and overall nonobese women (body mass index <30), IGF-I was a strong mediator, reducing the racial disparity in both cancers by 30% and 60%, respectively. In E-only users and nonusers, IGF-I explained the racial disparity in CR cancer only modestly. CONCLUSIONS: Bioavailable IGF-I is potentially important in racial disparities in obesity-related breast and CR cancer risk between postmenopausal AA and white women. Body fat distribution and E use may be part of the interconnected hormonal pathways related to racial difference in IGF-I levels and obesity-related cancer risk.
OBJECTIVE: Bioavailable insulin-like growth factor-I (IGF-I) interacts with obesity and exogenous estrogen (E) in a racial disparity in obesity-related cancer risk, yet their interconnected pathways are not fully characterized. We investigated whether circulating bioavailable IGF-I acted as a mediator of the racial disparity in obesity-related cancers such as breast and colorectal (CR) cancers and how obesity and E use regulate this relationship. METHODS: A total of 2,425 white and 164 African American (AA) postmenopausal women from the Women's Health Initiative Observational Study were followed from October 1, 1993 through August 29, 2014. To assess bioactive IGF-I as a mediator of race-cancer relationship, we used the Baron-Kenny method and quantitative estimation of the mediation effect. RESULTS: Compared with white women, AA women had higher IGF-I levels; their higher risk of CR cancer, after accounting for IGF-I, was no longer significant. IGF-I was associated with breast and CR cancers even after controlling for race. Among viscerally obese (waist/hip ratio >0.85) and overall nonobese women (body mass index <30), IGF-I was a strong mediator, reducing the racial disparity in both cancers by 30% and 60%, respectively. In E-only users and nonusers, IGF-I explained the racial disparity in CR cancer only modestly. CONCLUSIONS: Bioavailable IGF-I is potentially important in racial disparities in obesity-related breast and CR cancer risk between postmenopausal AA and white women. Body fat distribution and E use may be part of the interconnected hormonal pathways related to racial difference in IGF-I levels and obesity-related cancer risk.
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