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 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, food frequency questionnaire and 4-day food record 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 Alternative Healthy Eating Index 2010 calibration equations were 57.5% and 48.8% for food frequency questionnaire, 61.6% and 62.6% for 4-day food record, 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. Trial registration:  www.whi.org.