Lifestyle correlates of eight breast cancer-related metabolites: a cross-sectional study within the EPIC cohort

Abstract

Background Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2). Methods To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786). Results For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34:2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed. Conclusions These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated.

Diet and BMI Correlate with Metabolite Patterns Associated with Aggressive Prostate Cancer

“…Comparing these results to previous studies is complex; this analysis primarily investigated metabolite patterns rather than individual metabolites. Broadly in line with our results, however, positive associations of alcohol intake with some of the metabolites loading on metabolite pattern 1 (phosphatidylcholines and hydroxysphingomyelins) have previously been reported in other analyses [24][25][26][27].…”

“…The current analyses have identified dietary (fish and alcohol) and anthropometric (BMI) correlates of three metabolite patterns that were previously found to be inversely associated with more aggressive prostate cancer subtypes [1]. The implications of these associations are not yet clear; fish [33][34][35][36][37][38][39][40][41] and alcohol intakes [42][43][44][45][46][47][48][49][50][51] are not established risk factors for prostate cancer, while any associations of BMI with prostate cancer risk, of which positive associations with advanced disease and death have previously been reported [52], might be due to differences in the timing of detection of prostate cancer in men with obesity compared to men with a normal BMI [27,[53][54][55][56][57]. Furthermore, research is ongoing to determine whether the metabolite pattern-prostate cancer associations previously reported are likely to be causal.…”

Application of Metabolomics to Epidemiologic Studies of Breast Cancer: New Perspectives for Etiology and Prevention

“…A first approach is to build on the results of studies where novel metabolites were found to be associated with breast cancer risk, as in EPIC. 27 Concentrations of PCs ae C34:2, C36:2, C36:3, and C38:2 were found to be inversely associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also inversely associated with alcohol consumption and positively associated with a healthy lifestyle.…”

Impact of Lifestyle Interventions on Gynecologic Cancers: Beyond Diet and Exercise

“…The authors 54 found that reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity vs normal weight. 54 In another study, His and colleagues 55 evaluated the link between serum metabolite concentrations, lifestyle, adiposity, and breast cancer. Blood concentrations of acetylcarnitine, a metabolite, and breast cancer risk have been reported as well as lower risk associated with higher blood concentrations of seven other metabolites.…”