title: 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 = 1.02-1.38 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.
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: NaNa
authors.identifier: 0000-0003-4671-0211
authors.initials: N
authors.lastname: Keum
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Chen
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Biostatics, Harvard T.H. Chan School of Public Health, Boston, MA.|Division of MPE Molecular Pathological Epidemiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Reiko
authors.initials: R
authors.lastname: Nishihara
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Emilie
authors.initials: E
authors.lastname: Zoltick
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hamada
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martinez Fernandez
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hanyuda
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Department of Epidemiology and Biostatistics and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kosumi
authors.affiliation: Division of MPE Molecular Pathological Epidemiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Nowak
authors.affiliation: Division of MPE Molecular Pathological Epidemiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Iny
authors.initials: I
authors.lastname: Jhun
authors.affiliation: Division of MPE Molecular Pathological Epidemiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: T Rinda
authors.initials: TR
authors.lastname: Soong
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Fred K
authors.identifier: 0000-0001-8193-7150
authors.initials: FK
authors.lastname: Tabung
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
authors.affiliation: Department of Medicine, Yale School of Medicine, New Haven, CT.|Department of Medicine, Yale School of Medicine, New Haven, CT.|Smilow Cancer Hospital, New Haven, CT.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meyerhardt
authors.affiliation: Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Kimmie
authors.initials: K
authors.lastname: Ng
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Division of MPE Molecular Pathological Epidemiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.|Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.|Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Kana
authors.initials: K
authors.lastname: Wu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004032:Diet; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006282:Health Personnel / Q000706:statistics & numerical data; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D009726:Nurses / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D001786:Blood Glucose; D007328:Insulin
keywords: FASN; PIK3CA; colorectal cancer; colorectal cancer survival; glycemic index; glycemic load; insulin index; insulin load; insulin signaling pathway