Lin Yilong, Zhang Yue, Wang Songsong, Yang Qingmo
Department of Breast Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Department of Hematology, Xiangya Hospital, Xiangya School of Medicine, Central South University, Changsha, China.
Toxicol Appl Pharmacol. 2024 Mar;484:116855. doi: 10.1016/j.taap.2024.116855. Epub 2024 Feb 8.
The evidence about the causal roles of metabolites in breast cancer is lacking. This study conducted a systematic evaluation of the potential causal relationship between 1091 human blood metabolites, 309 metabolite ratios, and the likelihood of developing breast cancer and its subtype by employing a two-sample bidirectional Mendelian randomization (MR) approach Four metabolites, including tryptophan betaine (Odds Ratio [OR] = 1.07, 95%CI = 1.04-1.10, Bonferroni-corrected P = 0.007), X-21312 (OR = 0.90, 95%CI = 0.86-0.94, Bonferroni-corrected P = 0.02), 3-bromo-5-chloro-2,6-dihydroxybenzoic acid (OR = 0.94, 95%CI = 0.91-0.96, Bonferroni-corrected P = 0.03) and X-18921 (OR = 0.96, 95%CI = 0.94-0.98, Bonferroni-corrected P = 0.04) were significantly associated with overall breast cancer using inverse-variance weighted (IVW) method. Tryptophan betaine was also significantly associated with estrogen receptor (ER)-positive breast cancer (OR = 1.08, 95%CI = 1.04-1.11, Bonferroni-corrected P = 0.03). X-23680 (OR = 1.10, 95%CI = 1.05-1.15, Bonferroni-corrected P = 0.04) and glycine to phosphate ratio (OR = 1.07, 95%CI = 1.04-1.10, Bonferroni-corrected P = 0.04) were associated with ER-negative breast cancer. Reverse MR analysis showed no significant associations between breast cancer and metabolites. This MR study indicated compelling evidence of a causal association between metabolites and the risk of breast cancer and its subtypes, underscoring the potential impact of metabolic interference on breast cancer risk and indicating the drug targets for breast cancer.
关于代谢物在乳腺癌中因果作用的证据尚缺。本研究采用两样本双向孟德尔随机化（MR）方法，对1091种人体血液代谢物、309种代谢物比率与患乳腺癌及其亚型可能性之间的潜在因果关系进行了系统评估。使用逆方差加权（IVW）方法，四种代谢物，包括色氨酸甜菜碱（优势比[OR]=1.07，95%置信区间[CI]=1.04 - 1.10，经邦费罗尼校正P=0.007）、X - 21312（OR = 0.90，95%CI = 0.86 - 0.94，经邦费罗尼校正P = 0.02）、3 - 溴 - 5 - 氯 - 2,6 - 二羟基苯甲酸（OR = 0.94，95%CI = 0.91 - 0.96，经邦费罗尼校正P = 0.03）和X - 18921（OR = 0.96，95%CI = 0.94 - 0.98，经邦费罗尼校正P = 0.04）与总体乳腺癌显著相关。色氨酸甜菜碱也与雌激素受体（ER）阳性乳腺癌显著相关（OR = 1.08，95%CI = 1.04 - 1.11，经邦费罗尼校正P = 0.03）。X - 23680（OR = 1.10，95%CI = 1.05 - 1.15，经邦费罗尼校正P = 0.04）和甘氨酸与磷酸盐比率（OR = 1.07，95%CI = 1.04 - 1.10，经邦费罗尼校正P = 0.04）与ER阴性乳腺癌相关。反向MR分析显示乳腺癌与代谢物之间无显著关联。这项MR研究表明了代谢物与乳腺癌及其亚型风险之间存在因果关联的有力证据，强调了代谢干扰对乳腺癌风险的潜在影响，并指出了乳腺癌的药物靶点。
