Bowel Cancer: Wastewater Surveillance Shows Promise for Early Detection

Detecting a biomarker for bowel cancer – CDH1 – in wastewater could offer a novel, community-level early warning system for the disease, according to a proof-of-concept study published online in the Journal of Epidemiology & Community Health. The research suggests wastewater surveillance might complement existing screening programs and facilitate focus resources on areas where early detection efforts could be most effective, particularly as rates of bowel cancer are rising among younger adults.

In the United States, over 154,000 new cases of colorectal cancer are estimated annually, making it the third most common cancer and the second leading cause of cancer-related deaths. A key challenge is that the disease is often diagnosed at a late stage, reducing treatment options and survival rates. This new approach aims to shift that dynamic.

How Wastewater Surveillance Works

Wastewater, the water flushed from homes and businesses, contains a wealth of biological information shed in urine and feces. Researchers have successfully used wastewater to monitor for infectious diseases like polio and COVID-19. This study explores whether the same principle could apply to cancer detection. The premise is that detectable levels of cancer-related biomarkers in wastewater could signal a higher prevalence of the disease within a community.

The study, led by researchers at the University of Louisville, focused on Jefferson County, Kentucky. They analyzed data from patients treated for bowel cancer at a local tertiary care center between 2021 and 2023, identifying geographical areas with a high concentration of cases. These “clusters” were defined as areas with more than four bowel cancer cases within a half-mile radius. Researchers then compared cancer incidence rates from these clusters with state cancer registry data spanning 1995 to 2018.

Four geographical areas were selected for wastewater analysis: three with high bowel cancer incidence and one control area where few patients from the tertiary care center or state registry lived. Samples were collected three times from each of the four sewersheds on July 26, 2023, at 7:00, 10:00, and 13:00 hours.

CDH1 and GAPDH: The Biomarkers Analyzed

The researchers analyzed the wastewater samples for two key compounds: CDH1 and GAPDH. CDH1 is a gene associated with hereditary diffuse gastric cancer and lobular breast cancer, but its presence can also be an indicator of colorectal cancer. Research published in 2022 highlights the association between CDH1 germline variants and colon polyp phenotypes. GAPDH (glyceraldehyde 3-phosphate dehydrogenase) served as a control marker, indicating general cell maintenance and providing a baseline for comparison.

All samples from all four areas showed detectable levels of both compounds. However, the levels of CDH1 relative to GAPDH varied significantly. Cluster 1 exhibited the highest levels, with an average CDH1/GAPDH ratio of 20, while Cluster 2 had a ratio of 2.2, and Cluster 3 had a ratio of 4. The control cluster showed the lowest ratio at 2.6.

The researchers noted that Cluster 1 had more than double the number of known patients from the tertiary care center per 100 people compared to the other two clusters, potentially explaining the higher biomarker levels. They also acknowledged that some residents in the control cluster may have received cancer treatment elsewhere, influencing the results.

What the Findings Mean – and What They Don’t

This study is a crucial first step, demonstrating the feasibility of detecting cancer biomarkers in wastewater. The variation in CDH1/GAPDH ratios across the clusters suggests a potential correlation between biomarker levels and cancer incidence. However, it’s key to emphasize that this is a proof-of-concept study with several limitations.

The researchers caution that it’s currently unclear how the CDH1:GAPDH ratio in wastewater directly relates to the number of new bowel cancer cases. It’s also unknown whether the detected biomarkers represent diagnosed or undiagnosed cases. The small sample size and limited geographical scope further restrict the generalizability of the findings. According to Facing Our Risk, individuals with a CDH1 mutation have an increased risk for lobular breast cancer and hereditary diffuse gastric cancer.

The sensitivity and specificity of this wastewater-based approach for detecting bowel cancer biomarkers require validation in larger and more diverse populations. Further research is needed to determine the optimal sampling methods, biomarker thresholds, and data analysis techniques.

The Context of Rising Colorectal Cancer Rates

The study’s findings are particularly relevant given the concerning trend of increasing colorectal cancer incidence, especially among younger adults. Traditional screening methods, such as colonoscopy and stool-based tests, are effective but rely on individual participation. This can be a barrier for communities facing social and economic challenges.

Wastewater surveillance offers a potentially non-invasive and cost-effective way to monitor cancer prevalence at the community level. By detecting elevated biomarker levels across broader areas, public health officials could target specific regions for more intensive screening efforts. This approach could lead to earlier diagnosis and improved outcomes, particularly in underserved populations.

Public Health Implications and Next Steps

The researchers suggest that this approach could also help identify areas with a lower likelihood of case discovery, allowing for timely alerts to clinicians. This proactive approach could complement existing screening programs and contribute to a more comprehensive cancer surveillance system.

However, several steps are needed before wastewater surveillance can be implemented as a routine public health practice. Larger-scale studies are required to validate the findings and establish reliable biomarker thresholds. Standardized protocols for sample collection, analysis, and data interpretation are also essential. The United States Multi-Society Task Force on Colorectal Cancer currently recommends starting regular screening at age 45.

Future research should also investigate the potential for detecting biomarkers for other types of cancer in wastewater. This could pave the way for a broader, more comprehensive approach to cancer surveillance and prevention. The study authors emphasize the need for a collaborative research agenda to explore the full potential of wastewater-based epidemiology for population health monitoring.