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 ultra-high-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 square 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 contaminants exposure and colorectal cancer risk. Further research in this area is
needed to better understand the causal relationship and public health implications.