Plasma carotenoids, Vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort

Marije F. Bakker, Petra H M Peeters, Veronique M. Klaasen, H. Bas Bueno-De-Mesquita, Eugene H J M Jansen, Martine M. Ros, Noémie Travier, Anja Olsen, Anne Tjønneland, Kim Overvad, Sabina Rinaldi, Isabelle Romieu, Paul Brennan, Marie Christine Boutron-Ruault, Florence Perquier, Claire Cadeau, Heiner Boeing, Krasimira Aleksandrova, Rudolf Kaaks, Tilman KühnAntonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Paolo Vineis, Vittorio Krogh, Salvatore Panico, Giovanna Masala, Rosario Tumino, Elisabete Weiderpass, Guri Skeie, Eiliv Lund, J. Ramón Quirós, Eva Ardanaz, Carmen Navarro, Pilar Amiano, María José Sánchez, Genevieve Buckland, Ulrika Ericson, Emily Sonestedt, Matthias Johansson, Malin Sund, Ruth C. Travis, Timothy J. Key, Kay Tee Khaw, Nick Wareham, Elio Riboli, Carla H. Van Gils

Research output: Contribution to journalArticlepeer-review


Background: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity. Objective: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer. Design: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER2) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided. Results: In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER2 breast tumors. The other analytes were not statistically associated with ER2 breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER2 and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER2/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution). Conclusion: Our results indicate that higher concentrations of plasma β-carotene and α-carotene are associated with lower breast cancer risk of ER2 tumors.

Original languageEnglish
Pages (from-to)454-464
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Issue number2
Publication statusPublished - Feb 1 2016


  • Antioxidants
  • Breast cancer
  • Carotenoids
  • EPIC
  • Plasma

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


Dive into the research topics of 'Plasma carotenoids, Vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort'. Together they form a unique fingerprint.

Cite this