Metabolomics links lifestyle variables to breast cancer in the Long Island Breast Cancer Study Project

Abstract

Background/Aim: Healthy lifestyle has been associated with decreased risk of developing breast cancer. Using untargeted metabolomics profiling, we aim to identify the molecular mechanisms connecting lifestyle and breast cancer through network analysis. Methods: A total of 50 post-menopausal women with breast cancer and 50 cancer-free controls were selected from the Long Island Breast Cancer Study Project (LIBCSP). We measured untargeted plasma metabolomics using liquid chromatography- high resolution mass spectrometry (LC-HRMS). Using ‘enet’, we retained metabolites found in active molecular network (AMN) clusters for analysis. LASSO was used to explore associations between cancer status and metabolites; 14 lifestyle related variables including smoking, physical activity, alcohol consumption, meat consumption, fruit and vegetables consumption, supplemental vitamin use; and 20 covariates including various reproductive factors. LASSO was repeated to explore associations between selected lifestyle factors and metabolites. Results were displayed as a network to uncover biological pathways linking lifestyle factors to breast cancer. Results: After filtering, 1797 metabolomics peaks in the plasma samples remained. Of these, 851 "active” metabolites were retained in 197 correlation AMN clusters. Through LASSO, breast cancer status was associated with 66 "active” metabolites. Several of these metabolites were also associated with lifestyle variables including meat consumption, alcohol consumption, and supplemental β-carotene, B12 and folate use. No individual lifestyle factors were directly associated with breast cancer status through LASSO, suggesting that metabolites may act as biological intermediaries between healthy lifestyle factors and breast cancer. In particular, 13-HPODE, a metabolite linked with inflammation, was associated with breast cancer status and connected to β-carotene supplement usage through an AMN. Conclusions: We found several plasma metabolites associated with both lifestyle factors and breast cancer status. These results suggest that inflammation may play a mechanistic role linking supplement usage to breast cancer status. Keywords: breast cancer, lifestyle factors, metabolomics, network analysis