Serum-based biomarker development for dietary macronutrient densities and their association with breast and colorectal cancer risk in a cohort of postmenopausal females.

BACKGROUND

Associations of the macronutrient composition of the diet with risks of postmenopausal breast and colorectal cancer (CRC) are uncertain, partly because of reliance on self-reported dietary data.

OBJECTIVES

This study aims to study biomarker development for several macronutrient component densities using serum and spot urine metabolomics and, when appropriate, to assess their associations with breast cancer and CRC risks in a Women's Health Initiative (WHI) cohort of postmenopausal United States females.

METHODS

We explored linear biomarker equations for log-transformed macronutrient component densities using fasting serum metabolomic profiles, with and without spot urine, in a WHI feeding study (n = 153). We used equations satisfying a cross-validated regression R2 (CV-R2) criterion to calculate potential biomarker values for 577 breast cancer cases and 181 CRC cases and their 1:1 matched controls. We used Cox regression with baseline stratification on matched pairs to examine dietary composition associations with cancer risk.

RESULTS

Serum-based biomarker equations for macronutrient component densities had CV-R2 values as follows: PUFA 46.7%, MUFA 36.3%, SFA 33.6%, carbohydrate: 32.3%, and protein: 29.4%. The inclusion of spot urine metabolites did not materially improve these values. In analyses including serum-based PUFA, MUFA, SFA, and carbohydrate densities, the breast cancer hazard ratios (HRs) (95% confidence intervals) for 20% increments in dietary densities were 0.98 (0.89, 1.07) for PUFA and 1.14 (0.97, 1.33) for MUFA. Corresponding CRC HRs were 0.98 (0.81, 1.17) and 1.46 (1.10, 1.93). Analyses based on food frequency questionnaires differed from these estimates for breast cancer but tended to agree for CRC. Intakes of dairy and meat products may help to explain observed associations.

CONCLUSIONS

In a population of United States postmenopausal females, dietary MUFA density was associated with an elevation in CRC risk. Breast cancer associations with biomarker-based macronutrient densities require further development. This trial was registered at clinicaltrials.gov as NCT00000611 (https://clinicaltrials.gov/study/NCT00000611).