Lifestyle correlates of eight breast cancerrelated metabolites: a cross-sectional study within the EPIC cohort
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His, M... [et al.]. Lifestyle correlates of eight breast cancer-related metabolites: a cross-sectional study within the EPIC cohort. BMC Med 19, 312 (2021). [https://doi.org/10.1186/s12916-021-02183-2]
SponsorshipInstitut National du Cancer (INCA) France 2015-166; International Agency for Research on Cancer - Fondation ARC; World Health Organization; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London; Danish Cancer Society; Ligue Contre le Cancer (France); Institut Gustave Roussy (France); Mutuelle Generale de l'Education Nationale (France); Institut National de la Sante et de la Recherche Medicale (Inserm); Deutsche Krebshilfe; German Cancer Research Center (DKFZ) (Germany); German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany); Federal Ministry of Education & Research (BMBF); Fondazione AIRC per la ricerca sul cancro; Compagnia di San Paolo; Consiglio Nazionale delle Ricerche (CNR); Netherlands Government; World Cancer Research Fund International (WCRF); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain); Junta de Andalucia; Regional Government of Asturias (Spain); Regional Government of Basque Country (Spain); Regional Government of Murcia (Spain); Regional Government of Navarra (Spain); Catalan Institute of Oncology-ICO (Spain); Swedish Cancer Society; Swedish Research Council; County Council of Skane (Sweden); County Council of Vasterbotten (Sweden); Cancer Research UK 14136 C8221/A29017; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 1000143 MR/N003284/1 MC-UU_12015/1 MC_UU_00006/1 MR/M012190/1
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.