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Background  We examined the role of the insulinemic potential of diet and lifestyle in the development of cancers of the digestive system, using two plasma C-peptide-based indices: the empirical dietary index for hyperinsulinemia (EDIH) and empirical lifestyle index for hyperinsulinemia (ELIH).    Methods  We used Cox regression to analyze data on 45 816 men (Health Professionals Follow-up Study, 1986–2012) and 74 191 women (Nurses’ Health Study, 1984–2012) to examine associations between EDIH and ELIH scores and digestive system cancers. We computed the diet-only score (EDIH) from food-frequency questionnaires administered every 4 years. The lifestyle score (ELIH) included diet, body mass index, and physical activity. Outcomes included incident cancer of the digestive system (mouth, throat, esophagus, stomach, small intestine, and colorectum) and its accessory organs (pancreas, gallbladder, and liver).  P  values were two-sided.    Results  We found direct associations between higher insulinemic potential of diet or lifestyle and risk of developing digestive system cancers in both men and women. The pooled multivariable hazard ratios (HRs) for participants comparing the highest to lowest EDIH quintile were: HR = 1.27, 95% confidence interval (CI) = 1.15 to 1.40,  P  trend  < .001 for digestive system cancers; HR = 1.30, 95% CI = 1.17 to 1.45,  P  trend  < .001 for digestive tract cancers (excluding accessory organs); and HR = 1.15, 95% CI = 0.93 to 1.41,  P  trend  = .48 for digestive accessory organ cancers. The same associations were stronger with the lifestyle score: HR = 1.47, 95% CI = 1.23 to 1.76,  P  trend  < .001 for digestive system cancers; HR = 1.49, 95% CI = 1.14 to 1.95,  P  trend  = .001 for digestive tract cancers; and HR = 1.43, 95% CI = 1.17 to 1.73,  P  trend  < .001 for digestive accessory organ cancers.    Conclusions  The findings suggest that interventions to reduce the insulinemic potential of diet and lifestyle may be a means of preventing digestive system cancer.

Association of the Insulinemic Potential of Diet and Lifestyle With Risk of Digestive System Cancers in Men and Women