Causal role of blood metabolites in HER-positive and HER-negative breast cancer: a Mendelian randomization (MR) study.

BACKGROUND

Previous studies provide evidence that metabolites are associated with breast cancer (BC). However, the causal relationship between blood metabolites and BC remains unclear.

METHOD

Comprehensive two-sample Mendelian randomization analysis was conducted to determine the causal association between 1400 publicly available genetic data on metabolic factors and human epidermal growth factor receptor positive (HER+) BC or HER- BC in this study.

RESULT

Epiandrosterone sulfate levels (OR = 1.07, 95% CI = 1.02 ~ 1.10, = 0.0013), 5alpha-androstan-3beta,17beta-diol monosulfate (2) levels (OR = 1.07, 95% CI = 1.03 ~ 1.12, = 0.0012), glycohyocholate levels (OR = 0.85, 95% CI = 0.77 ~ 0.93, = 0.0007) and etiocholanolone glucuronide levels (OR = 1.12, 95% CI = 1.05 ~ 1.20, = 0.0013) were causally correlated with HER+ BC. 5 metabolites were causally correlated with HER- BC: Vanillic acid glycine levels (OR = 1.14, 95% CI = 1.06 ~ 1.22, = 0.0003), Thyroxine levels (OR = 1.26, 95% CI = 1.11 ~ 1.44, = 0.0004), 1-palmitoyl-2-linoleoyl-GPI (16:0/18:2) levels (OR = 0.86, 95% CI = 0.79 ~ 0.94, = 0.0010), N-acetylphenylalanine levels (OR = 1.12, 95% CI = 1.05 ~ 1.19, = 0.0007) and Glucose-to-mannose ratio (OR = 1.15, 95% CI = 1.06 ~ 1.24, = 0.0008). Two common causally related metabolites were identified: Gamma-glutamyl glutamate and X-12849 levels.

CONCLUSIONS

Our study has respectively demonstrated the connection between blood metabolites and HER+ or HER- BC by genetic means, thereby offering opportunities for therapeutic targets.