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Diet-Related Metabolites Associated with Breast Cancer Risk Factors

 A recent study used nutritional metabolomics to identify diet-related metabolites as potential breast cancer risk factors. The findings show that prediagnostic serum concentrations of metabolites related to alcohol, vitamin E, and animal fats were associated with an increased breast cancer risk.

Breast cancer is currently the leading global cause of cancer-related deaths in women. There is growing evidence for the role of dietary factors in breast cancer pathophysiology. However, most of the findings have been inconsistent and inconclusive regarding specific dietary exposures associated with breast cancer risk, possibly due to self-reported dietary assessments used in previous population based studies. Metabolomics, the study of identifying dietary metabolites using sophisticated analytical technologies to help explain diet-related health outcomes, provides a means to overcome the limitation imposed by self-reported dietary data. Nutritional metabolomics allows for simultaneous evaluation of several diet-related exposures and the metabolic processes they influence. Thus, metabolomics provides a means to accurately evaluate biomarkers that mediate diet-cancer relations.

A recent study published in The American Journal of Clinical Nutrition used a nutritional metabolomics approach to examine diet-related metabolite associations with subsequent breast cancer risk. Mary C Playdon and colleagues conducted a nested case-control study of prediagnostic serum concentrations of diet-related metabolites and post-menopausal breast cancer in women in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer screening trial cohort. The objective of the study was to use the more sensitive and comprehensive metabolomics platform to replicate and expand the diet-related metabolites identified in previous studies as well as evaluate relations between diet-related metabolites and breast cancer risk. The results were stratified by Estrogen Receptor (ER) status.

Prediagnostic serum concentrations of diet related metabolites were examined in 621 postmenopausal women with invasive breast cancer and 621 matching controls. Partial Pearson correlation between 617 metabolites and 55 foods, food groups, and vitamin supplements was calculated based on 2015 Dietary Guidelines for Americans and derived from a 137-item self-administered food frequency questionnaire. Diet-related metabolites were evaluated in breast cancer analysis. Odds Ratio (OR) for the 90th vs. 10th percentile for the associations between diet-related metabolites and breast cancer risk were calculated using conditional logistics regression.

There were 617 identifiable serum metabolites evaluated, of which 133 were found to be significantly associated with more than one dietary exposures. Three out of these 113 diet-related metabolites were associated with overall breast cancer risk- butter related caprate, a saturated fatty acid; dessert-related g-carboxyethyl hydrochroman (CEHC), a vitamin E derivative and alcohol related 4 androsten-3b,17b-diol-monosulfate, an androgen.

A total of 19 metabolites were significantly associated with Estrogen Receptor positive breast cancer. Two of these were butter-related caprate; 1 was fried food-related; 12 were alcohol related, and 3 were vitamin E (tocopherol)-related. Vitamin E had a positive or inverse association with ER+ breast cancer depending on the tocopherol isomer. Metabolites associated with margarine (g-CEHC glucuronide), desserts ((g-CEHC), and butter (caprate) were positively but not significantly associated with ER- breast cancer.

The authors claim that this was the first study to use metabolomics to evaluate pre-diagnostic circulating diet-related metabolites for breast cancer risk analysis. The large study size, the large number of metabolites identified, and stability of metabolomics platform are some of the strengths of this study. In addition, the serum samples collected were pre-diagnostic and cases and controls were handled comparably. The study also had a few limitations. Serum samples were obtained one year after the participants filled in the food frequency questionnaire. The analysis was restricted to identified metabolites measured by metabolomics platform and the study was underpowered to detect ER- breast cancer associations. Furthermore, the study population was mainly white postmenopausal women; therefore, results cannot be generalized to a diverse population.

The findings of this study imply the role of diet in postmenopausal breast cancer etiology. Pre-diagnostic serum concentrations of metabolites related to alcohol, vitamin E, and animal fats were found to have a moderately strong association with ER+ breast cancer risk. Nutritional metabolomics should be further applied in future studies to generate better understanding about 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



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