A. Jin1, S. Kavalukas1, N. DuPre2 1University Of Louisville, Surgery, Louisville, KY, USA 2University Of Louisville, School Of Public Health And Informational Sciences, Louisville, KY, USA
Introduction:
Colorectal cancer (CRC) is the third most common and third most deadly cancer in the U.S., with a rising incidence among the Early Onset (<50 years old) population. Despite achieving an acceptable 70% screening rate for CRC, our state has the highest age-standardized CRC rate in the country. To date, there has been very little investigation into the role of environmental toxins that may contribute to these elevated CRC rates. Cadmium (Cd) and arsenic (As) are known human carcinogens, though past data have primarily focused on occupational exposures and their relation to CRC incidence and mortality. Until now, no one has investigated the role of these toxins in ambient exposures, nor have individual-level biospecimen data been collected.
Methods:
A pilot study was initiated in August 2023 as a clinical case-control study. CRC cases and controls were recruited from a tertiary care center undergoing procedures related to CRC cancer or screening. Participants completed a detailed questionnaire and provided urine and blood samples. As and Cd were measured using inductively coupled plasma mass spectrometer (ICP-MS) in 80 urine samples (31 CRC cases; 49 controls) and in 85 whole blood samples (27 CRC cases; 58 controls). Urinary metal concentrations were creatinine-normalized. Logistic regression was used to estimate Odds Ratios (OR) and 95% Confidence Intervals (CI) to estimate CRC incidence for a standard deviation increase in each metal adjusted for major CRC risk factors, and separately conducted this analysis among never smokers (60%).
Results:
For a standard deviation increase in each metal, the odds of Cd were 1.14 times higher for urinary As (95% CI: 0.66-1.96), 1.09 times higher for urinary cadmium (95% CI: 0.78-1.53), 1.03 times higher for blood arsenic (95% CI:0.58-1.82), and 1.19 times higher for blood cadmium (95% CI:0.80-1.79) after adjusting for age, gender, family history of colorectal cancer, and any history of smoking. Among “never smokers”, the urinary analysis was similar to the above findings, with wider 95% CI (uAs adjusted OR=1.21 95% CI 0.53, 2.75); (uCd adjusted OR=1.1 95% CI 0.47, 2.59). Blood metal results differed, albeit still not statistically significant (blood As adjusted OR=1.33 95% CI 0.61, 2.87; blood Cd adjusted OR=0.58 95% CI 0.17, 1.96).
Conclusion:
This is the first study to evaluate individual-level measurements of ambient exposures to environmental toxins and its relation to CRC. While the results are not statistically significant due to small sample sizes, this preliminary data suggests that these metals may be associated with higher CRC incidence in non-occupationally exposed individuals and non-smoking populations. The results are encouraging for ongoing investigation to determine whether carcinogenic metals may be novel CRC risk factors.