TY - JOUR
T1 - Dietary glycemic and insulin scores and colorectal cancer survival by tumor molecular biomarkers
AU - Keum, Na Na
AU - Yuan, Chen
AU - Nishihara, Reiko
AU - Zoltick, Emilie
AU - Hamada, Tsuyoshi
AU - Martinez Fernandez, Alejandro
AU - Zhang, Xuehong
AU - Hanyuda, Akiko
AU - Liu, Li
AU - Kosumi, Keisuke
AU - Nowak, Jonathan A.
AU - Jhun, Iny
AU - Soong, T. Rinda
AU - Morikawa, Teppei
AU - Tabung, Fred K.
AU - Qian, Zhi Rong
AU - Fuchs, Charles S.
AU - Meyerhardt, Jeffrey A.
AU - Chan, Andrew T.
AU - Ng, Kimmie
AU - Ogino, Shuji
AU - Giovannucci, Edward L.
AU - Wu, Kana
N1 - Publisher Copyright:
© 2017 UICC
PY - 2017/6/15
Y1 - 2017/6/15
N2 - 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.
AB - 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.
KW - colorectal cancer
KW - colorectal cancer survival
KW - FASN
KW - glycemic index
KW - glycemic load
KW - insulin index
KW - insulin load
KW - insulin signaling pathway
KW - PIK3CA
UR - http://www.scopus.com/inward/record.url?scp=85017129645&partnerID=8YFLogxK
U2 - 10.1002/ijc.30683
DO - 10.1002/ijc.30683
M3 - Article
C2 - 28268248
AN - SCOPUS:85017129645
SN - 0020-7136
VL - 140
SP - 2648
EP - 2656
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 12
ER -