Associations of serum lead with colorectal cancer: data from NHANES 1999-2020

Background: Exposure to lead, a harmful heavy metal, is one of the risk factors for the development of Colorectal cancer (CRC). However, limited information is available on the impact of serum lead on the incidence of CRC. Therefore, this study utilized data from the National Health and Nutrition Examination Survey (NHANES) to explore the relationship between serum lead and CRC. Methods: A total of 32,894 American adults from the 1999-2020 NHANES cycles were included in this study, among whom 225 reported having CRC. Additionally, we also collected data on 3,024 other cancer patients from the same period. Weighted logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for the risk of CRC associated with serum lead, with adjustments for potential confounding factors. Restricted cubic spline (RCS) analysis was conducted to examine the dose-response relationship between serum lead and the risk of CRC. Concurrently, we performed propensity score matching (PSM) analysis and validated our conclusions through ICP-MS quantification in clinical tissue specimens. Results: This study revealed that patients diagnosed with CRC exhibited significantly elevated serum lead levels in comparison to both the general population and other cancer cohorts. Weighted logistic regression analysis showed a significant positive correlation between serum lead and the risk of CRC with or without adjusting for sociodemographic variables, BMI, diabetes, hypertension, and other covariates. The RCS model detected a dose-response relationship. Subgroup analysis indicated that the association between serum lead and CRC was similar across different sociodemographic characteristics, health behaviors, and comorbidities. However, the risk of CRC increased with higher serum lead levels among individuals aged ≥45, males, whites, BMI ≥24, alcohol users, smokers, and patients with diabetes. Despite the lack of statistically significant differences in lead levels after PSM analysis-potentially attributable to cohort size variations-our ultimate ICP-MS quantification of clinical tissues revealed markedly elevated lead concentrations in CRC specimens (p <0.0001). Conclusion: This cross-sectional study indicates a significant positive correlation between serum lead and the risk of CRC. Further prospective studies are needed to confirm these findings and elucidate the underlying mechanisms.