Hyperinsulinemic and Pro-Inflammatory Dietary Patterns and Metabolomic Profiles Are Associated with Increased Risk of Total and Site-Specific Cancers among Postmenopausal Women

SIMPLE SUMMARY: We investigated whether dietary patterns of insulinemia, inflammation and overall dietary quality are associated with the risk of total cancer, site-specific cancers, and pathological subtypes among postmenopausal women. We followed 112,468 women, 50–79 years of age, in the Women’s Health Initiative for a median of 17.8 years, documenting 18,768 incident invasive cancers. A higher overall dietary quality was associated with lower risk of total cancer and colorectal cancer. The potential of the dietary pattern to contribute to higher insulinemia and inflammation was associated with greater risk of total cancer, colorectal cancer and more strongly associated with risk of endometrial cancer and breast cancer (including triple negative breast cancer) than overall dietary quality. Additionally, a higher score of metabolites reflecting higher dietary quality was associated with lower lung cancer risk. Dietary patterns associated with cancer risk, therefore, warrant testing in clinical trials for cancer prevention among postmenopausal women. ABSTRACT: We evaluated associations of the Empirical Dietary Index for Hyperinsulinemia (EDIH), Empirical Dietary Inflammatory Pattern (EDIP) and Healthy Eating Index (HEI2015) and their metabolomics profiles with the risk of total and site-specific cancers. We used baseline food frequency questionnaires to calculate dietary scores among 112,468 postmenopausal women in the Women’s Health Initiative. We used multivariable-adjusted Cox regression to estimate hazard ratios (HR) and 95% confidence intervals for cancer risk estimation. Metabolomic profile scores were derived using elastic-net regression with leave-one-out cross validation. In over 17.8 years, 18,768 incident invasive cancers were adjudicated. Higher EDIH and EDIP scores were associated with greater total cancer risk, and higher HEI-2015 with lower risk: HR(Q5vsQ1)(95% CI): EDIH, 1.10 (1.04–1.15); EDIP, 1.08 (1.02–1.15); HEI-2015, 0.93 (0.89–0.98). The multivariable-adjusted incidence rate difference(Q5(vs)Q1) for total cancer was: +52 (EDIH), +41 (EDIP) and −49 (HEI-2015) per 100,000 person years. All three indices were associated with colorectal cancer, and EDIH and EDIP with endometrial and breast cancer risk. EDIH was further associated with luminal-B, ER-negative and triple negative breast cancer subtypes. Dietary patterns contributing to hyperinsulinemia and inflammation were associated with greater cancer risk, and higher overall dietary quality, with lower risk. The findings warrant the testing of these dietary patterns in clinical trials for cancer prevention among postmenopausal women.