Calibrated Dietary Patterns and Cancer Risk in the Women’s Health Initiative Cohorts

We developed calibration equations using metabolomics from fasting blood and 24-hour urine for Healthy Eating Index 2010 (HEI-2010) and Alternative Healthy Eating Index 2010 (AHEI-2010) to address measurement error from self-reported diet. We examined associations between metabolomic-calibrated dietary patterns and cancer risk in the Women's Health Initiative (WHI, n=108,522). Metabolomic signatures were created from a WHI Feeding (n=153;2010-2014) and WHI Observational Study (n=450;2006-2009). Dietary patterns were regressed on metabolites using the feeding study food intake records. Metabolomic-based dietary patterns were estimated from 24-hour dietary recalls, FFQ and 4DFR in the Observational Study using a stepwise approach. Cox regression estimated cancer risk of metabolomic-calibrated dietary patterns with a median follow-up of 15.8 years. Adjusted R2 for HEI-2010 and AHEI-2010 calibration equations were 57.5% and 48.8% for FFQ, 61.6% and 62.6% for 4DFR, and 52.5% and 53.2% for dietary recalls. Without calibration, a 20% increment in HEI-2010 was associated with lower risk of colorectal (HR=0.94, 95% CI=0.90-0.99), lung (HR=0.90, 95% CI=0.86-0.94), bladder (HR=0.86, 95% CI=0.75-0.99), and total invasive cancers (HR=0.98, 95% CI=0.96-0.99). With metabolomic calibration, higher HEI-2010 was associated with lower risk of lung (HR=0.79, 95% CI=0.71-0.88) and total invasive cancers (HR=0.96, 95% CI=0.92-1.00). Metabolomic-calibrated dietary patterns might mitigate measurement errors and strengthen diet-cancer associations.