A prospective study of the associations among fine particulate matter, genetic variants, and the risk of colorectal cancer.

BACKGROUND

Fine particulate matter (PM) is suspected to increase the risk of colorectal cancer, but the mechanism remains unknown. We aimed to investigate the association between PM exposure, genetic variants and colorectal cancer risk in the Prostate, Lung, Colon and Ovarian (PLCO) Cancer Screening trial.

METHODS

We included a prospective cohort of 139,534 cancer-free individuals from 10 United States research centers with over ten years of follow-up. We used a Cox regression model to assess the association between PM exposure and colorectal cancer incidence by calculating the hazard ratio (HR) and 95% confidence interval (CI) with adjustment for potential confounders. The polygenic risk score (PRS) and genome-wide interaction analysis (GWIA) were used to evaluate the multiplicative interaction between PM exposure and genetic variants in regard to colorectal cancer risk.

RESULTS

After a median of 10.43 years of follow-up, 1,666 participants had been diagnosed with colorectal cancer. PM exposure was significantly associated with an increased risk of colorectal cancer (HR = 1.27; 95% CI = 1.17-1.37 per 5 μg/m increase). Five independent susceptibility loci reached statistical significance at P < 1.22 × 10 in the interaction analysis. Furthermore, a joint interaction was observed between PM exposure and the PRS based on these five loci with colorectal cancer risk (P = 3.11 × 10). The Gene Ontology analysis showed that the vascular endothelial growth factor (VEGF) receptor signaling pathway was involved in the biological process of colorectal cancer.

CONCLUSIONS

Our large-scale analysis has shown for the first time that long-term PM exposure potential increases colorectal cancer risk, which might be modified by genetic variants.