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Using wastewater for population colorectal cancer screening and future research needs

Wurtzler, E.; Barnell, E.; Morrison, C.; Grass, C.; DuPre, N. C.; Biddle, D. J.; Jin, A.; Kavalukas, S.; Holm, R. H.; Smith, T. R.

2025-01-24 public and global health
10.1101/2025.01.22.25320996 medRxiv
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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the United States. Individual screening is typically done with either a clinical stool-based test or direct clinical examination such as a colonoscopy. Given the low compliance with current screening recommendations and the high morbidity and mortality observed in areas with health disparities, we consider whether population-based testing using human RNA biomarkers in wastewater might effectively track the presence of CRC at the neighborhood level might be feasible. Wastewater samples were collected from four clusters in Louisville, KY: three representing cancer hotspots and one serving as a control neighborhood for feasibility data. Three wastewater replicates were obtained from each cluster. Human RNA biomarkers were isolated, quantified, and their RNA concentration levels were compared to clinical correlates. All replicates showed detectable levels of human cancer-associated RNA, including CDH1, which is a colorectal neoplasia-associated biomarker. Among CRC cluster sewershed samples, 8 of 9 replicate samples (89%) had a ratio of CDH1/GAPDH >=1 while the control sewershed sample showed ratio <1 for 2 of 3 samples. These preliminary data indicate that human RNA biomarkers can be detected in pooled community wastewater samples. While we have successfully identified the presence of these markers, further investigation with additional samples and closer alignment with documented case activity is necessary.

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