Abstract
BACKGROUND: Reducing the incidence of breast cancer and improving its prognosis have become significant challenges for the global public health sector. We aimed to investigate the role of circulating triglycerides in the occurrence and survival of patients with breast cancer, while focusing on the possible differential effects by molecular subtypes of breast cancer. METHODS: We used a Mendelian randomization approach to analyze publicly accessible genome-wide association study data, including triglyceride levels, breast cancer risk, and survival prognosis. We performed a two-sample causality inference analysis using the inverse-variance weighted method. We used both Mendelian randomization-Egger regression and weighted median methods for model verification. Heterogeneity was evaluated using Cochran's Q test, and sensitivity analyses were performed using the leave-one-out method, Mendelian randomization-Egger intercept test, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier test. RESULTS: The results revealed a negative causal relationship between triglyceride levels and overall breast cancer risk (odds ratio [OR] = 0.94, confidence interval [CI] = 0.89-0.99, p = 0.011), luminal A breast cancer risk (OR = 0.93, CI = 0.87-0.99, p = 0.014), and human epidermal growth factor receptor 2 (HER2)-enriched breast cancer risk (OR = 0.84, CI = 0.73-0.96, p = 0.010). However, no statistically significant correlations were observed for the luminal B, luminal B HER2-negative, and triple-negative subtypes. Furthermore, triglyceride levels showed a positive causal relationship with the risk of survival prognosis in patients with estrogen receptor-negative breast cancer (OR = 1.33, CI = 1.00-1.76, p = 0.047). However, no statistically significant impact was observed on the survival of patients with overall breast cancer or patients with estrogen receptor-positive, HER2-positive, and HER2-negative breast cancer. CONCLUSIONS: The potentially complex role of circulating triglycerides in the incidence and survival of patients with breast cancer provides a new perspective on the heterogeneity of the effects of triglycerides on breast cancer, thereby promoting the development of precise medical strategies. Moreover, our findings contribute to an increased understanding of overall health among patients and clinicians alike.