Dietary glycemic and insulin scores and colorectal cancer survival by tumor molecular biomarkers

Na Na Keum, Chen Yuan, Reiko Nishihara, Emilie Zoltick, Tsuyoshi Hamada, Alejandro Martinez Fernandez, Xuehong Zhang, Akiko Hanyuda, Li Liu, Keisuke Kosumi, Jonathan A. Nowak, Iny Jhun, T. Rinda Soong, Teppei Morikawa, Fred K. Tabung, Zhi Rong Qian, Charles S. Fuchs, Jeffrey A. Meyerhardt, Andrew T. Chan, Kimmie NgShuji Ogino, Edward L. Giovannucci, Kana Wu

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Accumulating evidence suggests that post-diagnostic insulin levels may influence colorectal cancer (CRC) survival. Yet, no previous study has examined CRC survival in relation to a post-diagnostic diet rich in foods that increase post-prandial insulin levels. We hypothesized that glycemic and insulin scores (index or load; derived from food frequency questionnaire data) may be associated with survival from specific CRC subtypes sensitive to the insulin signaling pathway. We prospectively followed 1,160 CRC patients from the Nurses' Health Study (1980–2012) and Health Professionals Follow-Up Study (1986–2012), resulting in 266 CRC deaths in 10,235 person-years. CRC subtypes were defined by seven tumor biomarkers (KRAS, BRAF, PIK3CA mutations, and IRS1, IRS2, FASN and CTNNB1 expression) implicated in the insulin signaling pathway. For overall CRC and each subtype, hazard ratio (HR) and 95% confidence interval (95% CI) for an increase of one standard deviation in each of glycemic and insulin scores were estimated using time-dependent Cox proportional hazards model. We found that insulin scores, but not glycemic scores, were positively associated with CRC mortality (HR = 1.19, 95% CI = 1.02–1.38 for index; HR = 1.23, 95% CI = 1.04–1.47 for load). The significant positive associations appeared more pronounced among PIK3CA wild-type cases and FASN-negative cases, with HR ranging from 1.36 to 1.60 across insulin scores. However, we did not observe statistically significant interactions of insulin scores with PIK3CA, FASN, or any other tumor marker (p interaction > 0.12). While additional studies are needed for definitive evidence, a high-insulinogenic diet after CRC diagnosis may contribute to worse CRC survival.

Original languageEnglish
Pages (from-to)2648-2656
Number of pages9
JournalInternational Journal of Cancer
Volume140
Issue number12
DOIs
StatePublished - 15 Jun 2017

Keywords

  • colorectal cancer
  • colorectal cancer survival
  • FASN
  • glycemic index
  • glycemic load
  • insulin index
  • insulin load
  • insulin signaling pathway
  • PIK3CA

Fingerprint

Dive into the research topics of 'Dietary glycemic and insulin scores and colorectal cancer survival by tumor molecular biomarkers'. Together they form a unique fingerprint.

Cite this