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Observational Study
. 2019 Feb 1;111(2):170-179.
doi: 10.1093/jnci/djy098.

Dietary Insulin Load and Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803 (Alliance)

Vicente Morales-Oyarvide  1 , Chen Yuan  1 , Ana Babic  1 , Sui Zhang  1 , Donna Niedzwiecki  2 , Jennie C Brand-Miller  3 , Laura Sampson-Kent  4 , Xing Ye  2 , Yanping Li  4 , Leonard B Saltz  5 , Robert J Mayer  1 , Rex B Mowat  6 , Renaud Whittom  7 , Alexander Hantel  8 , Al Benson  9 , Daniel Atienza  10 , Michael Messino  11 , Hedy Kindler  12 , Alan Venook  13 , Shuji Ogino  1   14   15   16 , Kana Wu  4 , Walter C Willett  4   14 , Edward L Giovannucci  14   17 , Brian M Wolpin  1 , Jeffrey A Meyerhardt  1 , Charles S Fuchs  18 , Kimmie Ng  1
Affiliations
Observational Study

Dietary Insulin Load and Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803 (Alliance)

Vicente Morales-Oyarvide et al. J Natl Cancer Inst. .

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.

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Figures

Figure 1.
Figure 1.
Patient flow diagram. Exclusions based on caloric intake: women, less than 500 kilocalories or greater than 3500 kilocalories per day; men, less than 600 kilocalories or greater than 4200 kilocalories per day. Q1 = questionnaire 1; Q2 = questionnaire 2.
Figure 2.
Figure 2.
Kaplan-Meier survival curves by quintiles of dietary insulin load. A) Disease-free survival. B) Recurrence-free survival. C) Overall survival. All statistical tests were two-sided.
See this image and copyright information in PMC

Comment in

  • Too Early to Worry About Blueberries.
    Azrad M, Demark-Wahnefried W. Azrad M, et al. J Natl Cancer Inst. 2019 Feb 1;111(2):103-104. doi: 10.1093/jnci/djy101. J Natl Cancer Inst. 2019. PMID: 30768207 No abstract available.

References

    1. Meyerhardt JA, Heseltine D, Niedzwiecki D, et al. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: Findings from CALGB 89803. J Clin Oncol. 2006;2422:3535–3541. - PubMed
    1. Meyerhardt JA, Giovannucci EL, Holmes MD, et al. Physical activity and survival after colorectal cancer diagnosis. J Clin Oncol. 2006;2422:3527–3534. - PubMed
    1. Meyerhardt JA, Niedzwiecki D, Hollis D, et al. Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer. JAMA. 2007;2987:754–764. - PubMed
    1. Mills KT, Bellows CF, Hoffman AE, et al. Diabetes mellitus and colorectal cancer prognosis: A meta-analysis. Dis Colon Rectum. 2013;5611:1304–1319. - PMC - PubMed
    1. Wolpin BM, Meyerhardt JA, Chan AT, et al. Insulin, the insulin-like growth factor axis, and mortality in patients with nonmetastatic colorectal cancer. J Clin Oncol. 2009;272:176–185. - PMC - PubMed

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