Using wastewater for population-level colorectal cancer surveillance: a future research agenda

Individual screening for colorectal cancer (CRC) is typically performed through either direct clinical examination, such as a colonoscopy, or an approved non-invasive test that measures CRC markers shed from the tumour into stool. There are known barriers to current screening recommendations.

We present feasibility data demonstrating the detection of CRC-associated RNA biomarkers in community wastewater. RNA expression values for GAPDH (housekeeping marker) and CDH1 (colorectal neoplasia-associated marker) were quantified via droplet digital PCR. The CDH1 region evaluated in this study represents overall CDH1 concentration in wastewater samples, with elevated expression shown to be associated with colorectal neoplasia. Four neighbourhood clusters were assessed in this study: three CRC clusters (CRC Clusters #1-#3) and one control region (Control Cluster #1).

Average normalised colorectal neoplasia-associated RNA markers (CDH1/GAPDH) for CRC clusters were 20.0 (CRC Cluster #1), 2.2 (CRC Cluster #2) and 4.0 (CRC Cluster #3); average normalised colorectal neoplasia-associated RNA markers (CDH1/GAPDH) for Control Cluster #1 were 2.6.

Our data provide proof of principle for a novel application of wastewater surveillance to track potential cancer burden. We demonstrate that CDH1 is detectable in wastewater, potentially accelerating the development of this approach for epidemiological studies. Further investigation with additional samples and closer alignment with documented case activity will be necessary in future population-level CRC surveillance research.