Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Aging (Albany NY). 2024 Aug 2;16(15):11626-11655. doi: 10.18632/aging.206042.
Previous studies provide evidence that metabolites are associated with breast cancer (BC). However, the causal relationship between blood metabolites and BC remains unclear.
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.
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.
Our study has respectively demonstrated the connection between blood metabolites and HER+ or HER- BC by genetic means, thereby offering opportunities for therapeutic targets.
先前的研究表明，代谢物与乳腺癌（BC）有关。然而，血液代谢物与 BC 之间的因果关系尚不清楚。
本研究通过综合两样本孟德尔随机化分析，确定了 1400 项公开的代谢因子遗传数据与人类表皮生长因子受体阳性（HER+）BC 或 HER- BC 之间的因果关联。
硫酸表雄酮水平（OR=1.07，95%CI=1.021.10， = 0.0013）、5α-雄烷-3β，17β-二醇单硫酸盐（2）水平（OR=1.07，95%CI=1.031.12， = 0.0012）、甘氨胆酸水平（OR=0.85，95%CI=0.770.93， = 0.0007）和胆烷醇酮葡糖苷酸水平（OR=1.12，95%CI=1.051.20， = 0.0013）与 HER+BC 呈因果相关。5 种代谢物与 HER- BC 呈因果相关：香草酸甘氨酸水平（OR=1.14，95%CI=1.061.22， = 0.0003）、甲状腺素水平（OR=1.26，95%CI=1.111.44， = 0.0004）、1-棕榈酰-2-亚油酰基-GPI（16:0/18:2）水平（OR=0.86，95%CI=0.790.94， = 0.0010）、N-乙酰苯丙氨酸水平（OR=1.12，95%CI=1.051.19， = 0.0007）和葡萄糖-甘露糖比值（OR=1.15，95%CI=1.06~1.24， = 0.0008）。鉴定出两种常见的因果相关代谢物：γ-谷氨酰谷氨酸和 X-12849 水平。
本研究通过遗传手段分别证明了血液代谢物与 HER+或 HER- BC 之间的联系，从而为治疗靶点提供了机会。
