Study on Nutritional Metabolomics and Breast Cancer Risk

Introduction

A recent study has utilized nutritional metabolomics to identify diet-related metabolites that may serve as potential risk factors for breast cancer. The findings suggest that prediagnostic serum concentrations of metabolites associated with alcohol, vitamin E, and animal fats correlate with an increased risk of breast cancer. Currently, breast cancer remains the leading cause of cancer-related deaths among women globally.

Role of Dietary Factors

There is an increasing body of evidence highlighting the impact of dietary factors on the pathophysiology of breast cancer. However, previous research has often yielded inconsistent and inconclusive results regarding specific dietary exposures linked to breast cancer risk. This inconsistency may stem from reliance on self-reported dietary assessments used in earlier population-based studies.

Advancements in Metabolomics

Metabolomics, which involves the identification of dietary metabolites through advanced analytical technologies, offers a method to address the limitations of self-reported dietary data. This approach allows for the simultaneous evaluation of various diet-related exposures and the metabolic processes they influence, providing a more accurate assessment of biomarkers that mediate the relationship between diet and cancer.

Study Overview

A recent study published in *The American Journal of Clinical Nutrition* employed a nutritional metabolomics approach to investigate the associations between diet-related metabolites and subsequent breast cancer risk. Mary C Playdon and colleagues conducted a nested case-control study involving prediagnostic serum concentrations of diet-related metabolites and post-menopausal breast cancer in women from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer screening trial cohort. The study aimed to replicate and expand on diet-related metabolites identified in earlier research and evaluate their relationship with breast cancer risk, stratified by Estrogen Receptor (ER) status.

Methodology

The study analyzed prediagnostic serum concentrations of diet-related metabolites in 621 postmenopausal women diagnosed with invasive breast cancer and 621 matched controls. A partial Pearson correlation was calculated between 617 metabolites and 55 food items, food groups, and vitamin supplements, based on the 2015 Dietary Guidelines for Americans and a 137-item self-administered food frequency questionnaire. Odds Ratios (OR) for the associations between diet-related metabolites and breast cancer risk were computed using conditional logistic regression.

Key Findings

Out of 617 identifiable serum metabolites, 133 were significantly associated with multiple dietary exposures. Notably, three metabolites were linked to overall breast cancer risk: caprate (a saturated fatty acid related to butter), g-carboxyethyl hydrochroman (CEHC, a vitamin E derivative linked to desserts), and 4-androsten-3b,17b-diol-monosulfate (an alcohol-related androgen).

Furthermore, 19 metabolites showed significant associations with Estrogen Receptor positive (ER+) breast cancer. Among these, two were butter-related caprate, one was fried food-related, 12 were alcohol-related, and three were associated with vitamin E (tocopherol). The relationship between vitamin E and ER+ breast cancer risk varied depending on the tocopherol isomer. Additionally, metabolites linked to margarine, desserts, and butter were positively associated with ER- breast cancer, although not significantly.

Conclusions and Limitations

The authors assert that this study marks the first instance of using metabolomics to analyze pre-diagnostic circulating diet-related metabolites in relation to breast cancer risk. The study’s strengths include its large sample size, the number of metabolites identified, and the robustness of the metabolomics platform. Moreover, the serum samples were collected prior to diagnosis, ensuring comparable handling of cases and controls.

However, the study also faced limitations. Serum samples were collected one year after participants completed the food frequency questionnaire, and the analysis was confined to metabolites identifiable by the metabolomics platform. Additionally, the study was underpowered to detect associations with ER- breast cancer, and the predominantly white postmenopausal female population limits the generalizability of the results to a more diverse demographic.

Implications for Future Research

The findings suggest a significant role of diet in the etiology of postmenopausal breast cancer, particularly indicating that prediagnostic serum concentrations of metabolites related to alcohol, vitamin E, and animal fats have a moderately strong association with ER+ breast cancer risk. Future studies should continue to employ nutritional metabolomics to enhance the understanding of dietary metabolites as potential breast cancer risk factors.

Written by Preeti Paul, MS Biochemistry
Reference: Mary C Playdon, Regina G Ziegler et al; Nutritional metabolomics and breast cancer risk in a prospective study, AJCN, June 2017