Association between trans fatty acids and Subtypes of breast cancer: A Mendelian randomization study

Abstract

Abstract Conventional observational studies have revealed a potential correlation between trans fatty acids (TFAs) and breast cancer risk. However, there are inconsistencies among pertinent research findings, and well-powered analyses according to breast cancer subtypes have rarely been carried out. The relationship between TAFs and breast cancer subtypes was assessed using two-sample Mendelian randomization (MR). Genetic instruments were obtained from the European Pedigree TFAs of the CHARGE Consortium (n = 8013). Outcome GWAS summary statistics were obtained from the Breast Cancer Association Consortium (BCAC) on 122,977 cases and 105,974 controls of European ancestry. Out of them, 69,501 cases were identified as estrogen receptor (ER)-positive, and 21,468 cases were identified as ER-negative. The human epidermal growth factor receptor 2 (HER2) phenotype breast cancer cases were obtained from the FinnGen GWAS. Specifically, there were 12,783 instances of HER2-negative breast cancer (with 149,394 controls) and 7,729 cases of HER2-positive breast cancer (with 149,279 controls). We found that higher levels of circulating cis,trans-18:2 TFAs were positively associated with HER2-positive breast cancer (MR-Egger, p = 0.02, odds ratio [OR] = 6.403, 95% confidence interval [CI] = 1.565–26.194; IVW random-effects, p = 0.03, OR = 3.368, 95% CI: 1.080–10.507). The results of this extensive MR study provided evidence for a correlation between cis, trans-18:2TFAs, and HER2-positive breast cancer risk. We found no evidence of a causative relationship between TFAs and other subtypes of breast cancer, despite observational studies reporting a correlation between TFAs and breast cancer.