Merete Ellingjord-Dale1, Nikos Papadimitriou2, Michail Katsoulis3, Chew Yee1, Niki Dimou2, Dipender Gill1, Dagfinn Aune1,4,5, Jue-Sheng Ong6,7, Stuart MacGregor6, Benjamin Elsworth7, Sarah J Lewis7,8, Richard M Martin7,8,9, Elio Riboli1, Konstantinos K Tsilidis1,10. 1. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. 2. Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. 3. Institute of Health Informatics Research, Faculty of Population Health Sciences, University College London, London, United Kingdom. 4. Department of Nutrition, Bjørknes University College, Oslo, Norway. 5. Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway. 6. Statistical Genetics, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. 7. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom. 8. Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. 9. National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, United Kingdom. 10. Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.
Abstract
BACKGROUND: Observational studies have reported either null or weak protective associations for coffee consumption and risk of breast cancer. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the relationship between coffee consumption and breast cancer risk using 33 single-nucleotide polymorphisms (SNPs) associated with coffee consumption from a genome-wide association (GWA) study on 212,119 female UK Biobank participants of White British ancestry. Risk estimates for breast cancer were retrieved from publicly available GWA summary statistics from the Breast Cancer Association Consortium (BCAC) on 122,977 cases (of which 69,501 were estrogen receptor (ER)-positive, 21,468 ER-negative) and 105,974 controls of European ancestry. Random-effects inverse variance weighted (IVW) MR analyses were performed along with several sensitivity analyses to assess the impact of potential MR assumption violations. RESULTS: One cup per day increase in genetically predicted coffee consumption in women was not associated with risk of total (IVW random-effects; odds ratio (OR): 0.91, 95% confidence intervals (CI): 0.80-1.02, P: 0.12, P for instrument heterogeneity: 7.17e-13), ER-positive (OR = 0.90, 95% CI: 0.79-1.02, P: 0.09) and ER-negative breast cancer (OR: 0.88, 95% CI: 0.75-1.03, P: 0.12). Null associations were also found in the sensitivity analyses using MR-Egger (total breast cancer; OR: 1.00, 95% CI: 0.80-1.25), weighted median (OR: 0.97, 95% CI: 0.89-1.05) and weighted mode (OR: 1.00, CI: 0.93-1.07). CONCLUSIONS: The results of this large MR study do not support an association of genetically predicted coffee consumption on breast cancer risk, but we cannot rule out existence of a weak association.
BACKGROUND: Observational studies have reported either null or weak protective associations for coffee consumption and risk of breast cancer. METHODS: We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the relationship between coffee consumption and breast cancer risk using 33 single-nucleotide polymorphisms (SNPs) associated with coffee consumption from a genome-wide association (GWA) study on 212,119 female UK Biobank participants of White British ancestry. Risk estimates for breast cancer were retrieved from publicly available GWA summary statistics from the Breast Cancer Association Consortium (BCAC) on 122,977 cases (of which 69,501 were estrogen receptor (ER)-positive, 21,468 ER-negative) and 105,974 controls of European ancestry. Random-effects inverse variance weighted (IVW) MR analyses were performed along with several sensitivity analyses to assess the impact of potential MR assumption violations. RESULTS: One cup per day increase in genetically predicted coffee consumption in women was not associated with risk of total (IVW random-effects; odds ratio (OR): 0.91, 95% confidence intervals (CI): 0.80-1.02, P: 0.12, P for instrument heterogeneity: 7.17e-13), ER-positive (OR = 0.90, 95% CI: 0.79-1.02, P: 0.09) and ER-negative breast cancer (OR: 0.88, 95% CI: 0.75-1.03, P: 0.12). Null associations were also found in the sensitivity analyses using MR-Egger (total breast cancer; OR: 1.00, 95% CI: 0.80-1.25), weighted median (OR: 0.97, 95% CI: 0.89-1.05) and weighted mode (OR: 1.00, CI: 0.93-1.07). CONCLUSIONS: The results of this large MR study do not support an association of genetically predicted coffee consumption on breast cancer risk, but we cannot rule out existence of a weak association.
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