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

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 to 1.38 for index; HR=1.23, 95% CI=1.04 to 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 > .12). While additional studies are needed for definitive evidence, a high-insulinogenic diet after CRC diagnosis may contribute to worse CRC survival.

Influence of dietary insulin scores on survival in colorectal cancer patients

“…In this study, however, dietary insulin load and dietary insulin index were both strongly associated with worse patient outcome, suggesting that tumour progression among CRC patients may be influenced by acute postprandial insulin secretion in response to food intake. Our findings are consistent with a recent study using a subset of this population with measured tumour molecular markers ( N =1160), in which the overall HR for CRC-specific mortality was 1.19 (95% CI: 1.02–1.38) for an increase of one standard deviation in dietary insulin index ( Keum et al , 2017 ).…”

“…Among patients with non-metastatic CRC, elevated levels of plasma C-peptide were associated with an increased risk of CRC-specific mortality ( Wolpin et al , 2009 ). In addition, the association between dietary insulin scores and CRC survival appeared more apparent when CRC is negative for PIK3CA mutation and fatty acid synthase (FASN), two molecular markers linked to the insulin signalling pathway ( Keum et al , 2017 ). A recent study demonstrated that dietary sugar intake increases liver tumour incidence in female mice ( Healy et al , 2016 ), suggesting that a higher dietary insulin index may affect CRC progression by promoting metastasis to the liver.…”

Post-diagnosis dietary insulinemic potential and survival outcomes among colorectal cancer patients

“…Models were adjusted for age at diagnosis, post-diagnosis body mass index, total energy intake, sex, race, year of diagnosis, cancer stage, grade of tumor differentiation, location of primary tumor within the colon, post-diagnosis physical activity, post-diagnosis pack years of smoking, post-diagnosis regular aspirin use, weight change pre to postdiagnosis, post-diagnosis total alcohol intake, and pre-diagnosis EDIH score cancer prognosis has been inconsistent. Whereas one study found higher risk of colorectal cancer recurrence and death associated with higher glycemic load but not higher glycemic index [34]; another found no association between glycemic load or glycemic index and colorectal cancer survival [35]. Glycemic scores are primarily reflective of the postprandial glucose responses of carbohydrate-containing foods, whereas the EDIH score directly reflects insulin increases induced by components of the dietary pattern that may or may not be contributing to calories (e.g., coffee).…”

Lifestyle after Colorectal Cancer Diagnosis in Relation to Survival and Recurrence: A Review of the Literature

“…The dietary factors included in this review that might be linked to insulin-related pathways, a Western dietary pattern [ 23 , 42 ], sugar-sweetened beverages [ 23 , 43 ], low coffee consumption [ 25 ], and higher dietary glycemic load [ 45 ] all showed increased mortality risk. Also, a high-insulinogenic diet [ 98 ] has been associated with increased mortality risk. However, these studies were almost all conducted in the same cohort embedded in a trial of adjuvant chemotherapy (CALGB 89803) [ 25 , 42 , 43 , 45 ].…”