<br>一项西班牙多中心研究（MCC-Spain）中饮用水中硝酸盐和三卤甲烷暴露的代谢组学特征和结直肠癌风险,Environmental Science & Technology

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一项西班牙多中心研究（MCC-Spain）中饮用水中硝酸盐和三卤甲烷暴露的代谢组学特征和结直肠癌风险
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2023-11-14 , DOI: 10.1021/acs.est.3c05814
Jose A Alcolea _{1,

2,

3} , Carolina Donat-Vargas _{1,

2,

3,

4} , Anastasia Chrysovalantou Chatziioannou ₅ , Pekka Keski-Rahkonen ₅ , Nivonirina Robinot ₅ , Antonio José Molina _{6,

7} , Pilar Amiano _{2,

8} , Inés Gómez-Acebo _{2,

9} , Gemma Castaño-Vinyals _{1,

2,

3,

10} , Lea Maitre _{1,

2,

3} , Marc Chadeau-Hyam ₁₁ , Sonia Dagnino _{11,

12} , Sibo Lucas Cheng ₁₁ , Augustin Scalbert ₅ , Paolo Vineis ₁₁ , Manolis Kogevinas _{1,

2,

3,

10} , Cristina M Villanueva _{1,

2,

3,

10}

Affiliation

ISGlobal, c/Dr. Aiguader 88, Barcelona 08003, Spain.
CIBER Epidemiología y Salud Pública (CIBERESP), Avenida Monforte de Lemos, 3-5, Pabellón 11, Planta 0, Madrid 28029, Spain.
Universitat Pompeu Fabra (UPF), c/Doctor Aiguader 88, Barcelona 08003, Spain.
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden.
International Agency for Research on Cancer, 25 avenue Tony Garnier, CS 90627 69366, Lyon, France.
Research Group in Gene - Environment and Health Interactions (GIIGAS)/Institute of Biomedicine (IBIOMED), Universidad de León, Campus Universitario de Vegazana, León 24071, Spain.
Faculty of Health Sciences, Department of Biomedical Sciences, Area of Preventive Medicine and Public Health, Universidad de León, Campus Universitario de Vegazana, León 24071, Spain.
Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa; BioGipuzkoa (BioDonostia) Health Research Institute, San Sebastián 20013, Spain.
Universidad de Cantabria-IDIVAL, Avenida Cardenal Herrera Oria S/N, Santander 39011, Spain.
IMIM (Hospital del Mar Medical Research Institute), c/Doctor Aiguader 88, Barcelona 08003, Spain.
MRC Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom.
Transporters in Imaging and Radiotherapy in Oncology (TIRO), School of Medicine, Direction de la Recherche Fondamentale (DRF), Institut des Sciences du Vivant Frédéric Joliot, Commissariat à l'Energie Atomique et aux Énergies Alternatives (CEA), Université Côte d'Azur (UCA), 28 Avenue de Valombrose, Nice 06107, France.

我们调查了来自西班牙多病例对照项目的 296 例病例和 295 例对照中与饮用水中三卤甲烷（THM）和硝酸盐暴露相关的代谢组学特征以及与结直肠癌风险相关的代谢组学特征。使用超高效液相色谱-四极杆飞行时间质谱法对血液样品进行非靶向代谢组学分析。在数据质量控制、标准化和插补后进行各种单变量和多变量关联分析。对对照中的氯仿、溴化 THM、总 THM 和硝酸盐以及病例对照状态进行线性回归和偏最小二乘分析，以及通过询问暴露变量与代谢组学特征之间的相关性来区分结直肠癌病例与对照组的 N 整合模型。结果显示，共有 568 个代谢组学特征与至少一种水污染物或结直肠癌相关。注释的代谢物和通路分析表明，许多途径可能参与暴露于这些水污染物与结直肠癌之间的联系，包括烟酰胺、细胞色素 P-450 和酪氨酸代谢。这些发现为潜在的生物学机制和与水污染物暴露和结直肠癌风险相关的潜在生物标志物提供了见解。需要在这一领域进行进一步研究，以更好地了解因果关系和公共卫生影响。

"点击查看英文标题和摘要"

Metabolomic Signatures of Exposure to Nitrate and Trihalomethanes in Drinking Water and Colorectal Cancer Risk in a Spanish Multicentric Study (MCC-Spain)

We investigated the metabolomic profile associated with exposure to trihalomethanes (THMs) and nitrate in drinking water and with colorectal cancer risk in 296 cases and 295 controls from the Multi Case-Control Spain project. Untargeted metabolomic analysis was conducted in blood samples using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. A variety of univariate and multivariate association analyses were conducted after data quality control, normalization, and imputation. Linear regression and partial least-squares analyses were conducted for chloroform, brominated THMs, total THMs, and nitrate among controls and for case-control status, together with a N-integration model discriminating colorectal cancer cases from controls through interrogation of correlations between the exposure variables and the metabolomic features. Results revealed a total of 568 metabolomic features associated with at least one water contaminant or colorectal cancer. Annotated metabolites and pathway analysis suggest a number of pathways as potentially involved in the link between exposure to these water contaminants and colorectal cancer, including nicotinamide, cytochrome P-450, and tyrosine metabolism. These findings provide insights into the underlying biological mechanisms and potential biomarkers associated with water contaminant exposure and colorectal cancer risk. Further research in this area is needed to better understand the causal relationship and the public health implications.

更新日期：2023-11-14

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