Vicente Morales-Oyarvide1, Chen Yuan1, Ana Babic1, Sui Zhang1, Donna Niedzwiecki2, Jennie C Brand-Miller3, Laura Sampson-Kent4, Xing Ye2, Yanping Li4, Leonard B Saltz5, Robert J Mayer1, Rex B Mowat6, Renaud Whittom7, Alexander Hantel8, Al Benson9, Daniel Atienza10, Michael Messino11, Hedy Kindler12, Alan Venook13, Shuji Ogino1,14,15,16, Kana Wu4, Walter C Willett4,14, Edward L Giovannucci14,17, Brian M Wolpin1, Jeffrey A Meyerhardt1, Charles S Fuchs18, Kimmie Ng1. 1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. 2. Alliance Statistics and Data Center, Duke University, Durham, NC. 3. Institute of Obesity, Nutrition, and Exercise, University of Sydney, Sydney, Australia. 4. Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA. 5. Memorial Sloan Kettering Cancer Center, New York, NY. 6. Toledo Community Hospital Oncology Program, Toledo, OH. 7. Hôpital du Sacré-Coeur de Montréal, Montreal, Canada. 8. Loyola University Stritch School of Medicine, Naperville, IL. 9. Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL. 10. Virginia Oncology Associates, Norfolk, VA. 11. Southeast Clinical Oncology Research Consortium, Mission Hospitals, Asheville, NC. 12. University of Chicago Comprehensive Cancer Center, Chicago, IL. 13. University of California at San Francisco Comprehensive Cancer Center, San Francisco, CA. 14. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA. 15. Department of Pathology, Brigham and Women's Hospital, Boston, MA. 16. Department of Pathology, Harvard Medical School, Boston, MA. 17. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 18. Yale Cancer Center, Smilow Cancer Hospital and Yale School of Medicine, New Haven, CT.
Abstract
BACKGROUND: Evidence suggests that diets inducing postprandial hyperinsulinemia may be associated with increased cancer-related mortality. The goal of this study was to assess the influence of postdiagnosis dietary insulin load and dietary insulin index on outcomes of stage III colon cancer patients. METHODS: We conducted a prospective observational study of 1023 patients with resected stage III colon cancer enrolled in an adjuvant chemotherapy trial who reported dietary intake halfway through and six months after chemotherapy. We evaluated the association of dietary insulin load and dietary insulin index with cancer recurrence and survival using Cox proportional hazards regression adjusted for potential confounders; statistical tests were two-sided. RESULTS: High dietary insulin load had a statistically significant association with worse disease-free survival (DFS), comparing the highest vs lowest quintile (adjusted hazard ratio [HR] = 2.77, 95% confidence interval [CI] = 1.90 to 4.02, Ptrend < .001). High dietary insulin index was also associated with worse DFS (highest vs lowest quintile, HR = 1.75, 95% CI = 1.22 to 2.51, Ptrend= .01). The association between higher dietary insulin load and worse DFS differed by body mass index and was strongest among patients with obesity (HR = 3.66, 95% CI = 1.88 to 7.12, Pinteraction = .04). The influence of dietary insulin load on cancer outcomes did not differ by mutation status of KRAS, BRAF, PIK3CA, TP53, or microsatellite instability. CONCLUSIONS:Patients with resected stage III colon cancer who consumed a high-insulinogenic diet were at increased risk of recurrence and mortality. These findings support the importance of dietary management following resection of colon cancer, and future research into underlying mechanisms of action is warranted.
RCT Entities:
BACKGROUND: Evidence suggests that diets inducing postprandial hyperinsulinemia may be associated with increased cancer-related mortality. The goal of this study was to assess the influence of postdiagnosis dietary insulin load and dietary insulin index on outcomes of stage III colon cancerpatients. METHODS: We conducted a prospective observational study of 1023 patients with resected stage III colon cancer enrolled in an adjuvant chemotherapy trial who reported dietary intake halfway through and six months after chemotherapy. We evaluated the association of dietary insulin load and dietary insulin index with cancer recurrence and survival using Cox proportional hazards regression adjusted for potential confounders; statistical tests were two-sided. RESULTS: High dietary insulin load had a statistically significant association with worse disease-free survival (DFS), comparing the highest vs lowest quintile (adjusted hazard ratio [HR] = 2.77, 95% confidence interval [CI] = 1.90 to 4.02, Ptrend < .001). High dietary insulin index was also associated with worse DFS (highest vs lowest quintile, HR = 1.75, 95% CI = 1.22 to 2.51, Ptrend= .01). The association between higher dietary insulin load and worse DFS differed by body mass index and was strongest among patients with obesity (HR = 3.66, 95% CI = 1.88 to 7.12, Pinteraction = .04). The influence of dietary insulin load on cancer outcomes did not differ by mutation status of KRAS, BRAF, PIK3CA, TP53, or microsatellite instability. CONCLUSIONS:Patients with resected stage III colon cancer who consumed a high-insulinogenic diet were at increased risk of recurrence and mortality. These findings support the importance of dietary management following resection of colon cancer, and future research into underlying mechanisms of action is warranted.
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