Mahamat-Saleh Yahya, Merdas Mira, Viallon Vivian, Robinot Nivonirina, Biessy Carine, Jacobs Inarie, Taljaard-Krugell Christine, Zandberg Lizelle, Joffe Maureen, Gunter Marc J, Keski-Rahkonen Pekka, Dossus Laure, Rinaldi Sabina
Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.
Int J Cancer. 2025 Oct 15;157(8):1543-1556. doi: 10.1002/ijc.35503. Epub 2025 Jun 17.
The incidence of breast cancer has been steadily increasing in South Africa over the past decades, but this rise can only be partially attributed to changes in known modifiable risk factors. Metabolomics may help to elucidate novel biological pathways and identify potential biomarkers associated with cancer. We investigated the association between serum metabolites and breast cancer risk in black women from Soweto, South Africa. An untargeted ultra-high-performance LC-MS method was used to measure molecular features in serum samples from a total of 396 breast cancer cases and 396 population-based controls matched on age and demographic settings, enrolled in the South African Breast Cancer study. A total of 5820 features were detected from metabolomics analyses and 1732 were retained for statistical analysis after data pre-processing and imputation. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and false discovery rate-adjusted (FDR) confidence interval (CI) for the association of metabolite features and breast cancer risk. Overall, 12 molecular features were significantly associated with odds of breast cancer (FDR <0.05); 11 features were associated with increased odds of breast cancer, and 1 feature was associated with decreased odds of breast cancer. Of these, 7 metabolic features corresponding to 3 individual metabolites were identified. Serum levels of cortisol (OR = 1.63, 95% CI = 1.18-2.25 per 1 SD increase), kynurenine (OR = 1.38, 95% CI = 1.01-1.88), and octenoylcarnitine (OR = 1.46, 95% CI = 1.02-2.08) were associated with higher odds of breast cancer. This study suggests that metabolic pathways related to cortisol, kynurenine, and carnitine metabolism may play a role in black African women with breast cancer. These results need to be explored in prospective studies.
在过去几十年中，南非乳腺癌的发病率一直在稳步上升，但这种上升只能部分归因于已知可改变风险因素的变化。代谢组学可能有助于阐明新的生物学途径，并识别与癌症相关的潜在生物标志物。我们调查了南非索韦托黑人女性血清代谢物与乳腺癌风险之间的关联。采用非靶向超高效液相色谱-质谱法，对南非乳腺癌研究中纳入的396例乳腺癌病例和396例按年龄和人口统计学特征匹配的人群对照的血清样本中的分子特征进行测量。代谢组学分析共检测到5820个特征，经过数据预处理和插补后，保留1732个用于统计分析。采用多变量条件逻辑回归估计代谢物特征与乳腺癌风险关联的比值比（OR）和错误发现率调整（FDR）置信区间（CI）。总体而言，12个分子特征与乳腺癌几率显著相关（FDR<0.05）；11个特征与乳腺癌几率增加相关，1个特征与乳腺癌几率降低相关。其中，识别出对应于3种个体代谢物的7种代谢特征。皮质醇血清水平（每增加1个标准差，OR = 1.63，95%CI = 1.18 - 2.25）、犬尿氨酸（OR = 1.38，95%CI = 1.01 - 1.88）和辛酰肉碱（OR = 1.46，95%CI = 1.02 - 2.08）与乳腺癌更高几率相关。这项研究表明，与皮质醇、犬尿氨酸和肉碱代谢相关的代谢途径可能在患有乳腺癌的非洲黑人女性中起作用。这些结果需要在前瞻性研究中进一步探索。
