Nutrient-Wide Association Study of 92 Foods and Nutrients and Breast Cancer Risk

Alicia K. Heath; David C. Muller; Piet A. van den Brandt; Nikos Papadimitriou; Elena Critselis; Marc Gunter; Paolo Vineis; Elisabete Weiderpass; Guy Fagherazzi; Heiner Boeing; Pietro Ferrari; Anja Olsen; Anne Tjønneland; Patrick Arveux; Marie-Christine Boutron-Ruault; Francesca Romana Mancini; Tilman Kühn; Renée Turzanski-Fortner; Matthias B. Schulze; Anna Karakatsani; Paschalis Thriskos; Antonia Trichopoulou; Giovanna Masala; Paolo Contiero; Fulvio Ricceri; Salvatore Panico; Bas Bueno-de-Mesquita; Marije F. Bakker; Carla H. van Gils; Karina Standahl Olsen; Guri Skeie; Cristina Lasheras; Antonio Agudo; Miguel Rodríguez-Barranco; Maria-José Sánchez; Pilar Amiano; María-Dolores Chirlaque; Aurelio Barricarte; Isabel Drake; Ulrika Ericson; Ingegerd Johansson; Anna Winkvist; Tim Key; Heinz Freisling; Mathilde His; Inge Huybrechts; Sofia Christakoudi; Merete Ellingjord-Dale; Elio Riboli; Konstantinos K. Tsilidis; Ioanna Tzoulaki


Breast Cancer Res. 2020;22(5) 

In This Article


Dietary factors have been extensively investigated as possible risk factors for breast cancer, but overall evidence for associations is inconsistent and inconclusive.[1] Aside from alcohol intake, for which there is strong evidence of a positive association with breast cancer risk, no convincing dietary risk factors have been identified.[1,2]

Fruits and vegetables are of particular interest due to their rich content of nutrients and phytochemicals, which are thought to have anticarcinogenic effects.[3] However, epidemiological studies assessing intake of fruit and vegetables, as well as of other foods such as meat, dairy, and soy products, have yielded inconsistent results.[1,2,4,5] Dietary fat intake has also been widely investigated as a possible risk factor for breast cancer because it is thought to increase endogenous oestrogen levels;[6,7] however, there is overall limited evidence for an association[1] and results from prospective studies are conflicting.[2,6] Based on current evidence, the 2017 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Third Expert Report on diet, nutrition, physical activity, and breast cancer concluded there is suggestive but limited evidence that intake of non-starchy vegetables, carotenoid-containing foods, and diets high in calcium might be associated with a lower risk of breast cancer.[1] It is also possible that associations of foods and nutrients with breast cancer risk might differ by menopausal status,[1] hormone receptor status of tumours,[8] and molecular subtypes.[9] Due to inconsistencies in the existing literature, the potential role of diet in breast cancer aetiology remains unclear.

We systematically evaluated an extensive list of dietary factors in relation to breast cancer risk using a nutrient-wide association study (NWAS) approach. The NWAS takes an analogous strategy to that of genome-wide association studies (GWAS), separately estimating associations for each food and nutrient measured, and using multiple comparison adjustments to select promising associations for replication in an independent study.[10] This method has been used to investigate dietary risk associations for blood pressure,[11] endometrial cancer,[12] and epithelial ovarian cancer.[13]