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Publications

Journal Article Ahead of print

PubMed: 42520943 DOI: 10.1016/j.ajcnut.2026.101456

One-carbon metabolism nutrients and polygenic risk scores in relation to breast cancer risk: A nested case-control study within the EPIC cohort.

Am J Clin Nutr

Authors: José María Gálvez-Navas, Laia Peruchet-Noray, Esther Molina-Montes, Miguel Rodríguez-Barranco, Carine Biessy, Christian Skødt Antoniussen, Christina C Dahm, Cecilie Kyrø, Christina Dahl, Pierre-Emmanuel Sugier, Yazdan Asgari, Thérèse Truong, Geneviève Nicolas, Renée Turzanski-Fortner, Charlotte le Cornet, Matthias B Schulze, Lorenzo Milani, Giovanna Masala, Martina Quartiroli, Simona Signoriello, Rosario Tumino, Marta Crous-Bou, Olatz Mokoroa, Daniel Rodríguez-Palacios, Camino Trobajo-Sanmartín, Alicia K Heath, Laure Dossus, Inge Huybrechts, María-José Sánchez

Affiliations

  • Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Spain; Andalusian School of Public Health, Cuesta del Observatorio, 4, 18011, Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain.
  • Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Wood Lane, London W12 0HZ, United Kingdom; Nutrition and Metabolism Brach (NME), International Agency for Research on Cancer (IARC), Lyon, France.
  • Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Spain; Andalusian School of Public Health, Cuesta del Observatorio, 4, 18011, Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Department of Nutrition and Food Sciences, Faculty of Pharmacy, University of Granada, 18011, Granada, Spain.
  • Nutrition and Metabolism Brach (NME), International Agency for Research on Cancer (IARC), Lyon, France.
  • Department of Public Health, Aarhus University, Aarhus, Denmark.
  • Danish Cancer Institute, Copenhagen, Denmark.
  • Paris-Saclay University, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France; Université Paris Cité, CNRS, MAP5, Paris, France.
  • Paris-Saclay University, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France.
  • Hormones and Cancer Group, Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway.
  • Hormones and Cancer Group, Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
  • Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
  • Center for Biostatistics, Epidemiology, and Public Health, Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy.
  • Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
  • Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy.
  • Medical Statistics Unit, University "L. Vanvitelli", Naples, Italy.
  • Hyblean Association for Epidemiological Research, AIRE ONLUS Ragusa, Italy.
  • Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona 08908, Spain; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
  • Biogipuzkoa Health Research Institute, Group of Epidemiology of Chronic and Communicable Diseases, San Sebastián, Gipuzkoa, Spain; Ministry of Health of the Basque Government, Sub-Doctorate for Public Health and Addictions of Gipuzkoa, San Sebastián, Gipuzkoa, Spain.
  • Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Spain; Department of Epidemiology, Murcia Regional Health Council-IMIB, Murcia, Spain.
  • Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Spain; Instituto de Salud Pública y Laboral de Navarra, 31003 Pamplona, Spain; Navarre Institute for Health Research (IdiSNA), 31008, Pamplona, Spain.
  • Cancer Epidemiology and Prevention Unit, School of Public Health, Imperial College London, London, United Kingdom.

Abstract

BACKGROUND

One-carbon metabolism (1CM) regulates critical processes to carcinogenesis. However, the influence of 1CM-related nutritional and genetic factors on breast cancer (BC) risk remains unclear.

OBJECTIVE

To assess the impact of 1CM-related nutrients and genetic variants with BC risk.

METHODS

Case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 3067 incident BC cases and 3067 matched controls from seven European countries. Individual 1CM-nutrient intakes and nutritional scores for B-vitamins and all 1CM-related nutrients were evaluated. Dietary intakes were collected via country- and center-specific questionnaires. Tissue-specific polygenic risk scores (PRS) for lower expression of 1CM genes were developed using expression-quantitative-trait-loci (eQTLs) from BC-relevant tissues (mammary, adipose, hepatic, adrenal, ovarian and uterine). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for established risk factors. Interactions between nutritional scores and PRS, and between B-vitamins score and alcohol intake, were evaluated.

RESULTS

Per one standard deviation (OR 1-SD) of higher intakes of vitamin B2 (OR 1-SD 0.93; 95%CI 0.87, 0.99), vitamin B12 (OR 1-SD 0.94; 95%CI 0.89, 0.99) and B-vitamins score (OR 1-SD 0.97; 95%CI 0.95, 0.99), inverse associations were observed with BC risk. Lower expression of 1CM genes in adipose tissue was associated with higher risk among premenopausal females (OR 1.12; 95%CI 1.02, 1.23) but not among postmenopausal women. The inverse association between B-vitamins score and BC risk varied by alcohol consumption (β =0.010; 95%CI 0.001, 0.021; P = .044); this association was not observed among females consuming more than 16 g/d of alcohol. No nutritional score-PRS interactions were observed.

CONCLUSION

Higher intake of B-vitamins was associated with reduced BC risk. Adipose tissue-specific downregulation of 1CM genes may differentially influence BC risk by menopausal status. These findings support the biological plausibility of 1CM in breast carcinogenesis and highlight the potential importance of adequate B-vitamin intake.

MeSH

Nutrients, Genes, Breast Neoplasms, Vitamins, Case-Control Studies, Neoplasms, Food, Breast, Carcinogenesis, Nutritional Physiological Phenomena, Tissues, Alcohol Drinking, Genetic Risk Score