DNA Methylation-Derived Immune Cell Proportions and Cancer Risk in Black Participants.

Prior cohort studies assessing cancer risk based on immune cell subtype profiles have predominantly focused on White populations. This limitation obscures vital insights into how cancer risk varies across race. Immune cell subtype proportions were estimated using deconvolution based on leukocyte DNA methylation markers from blood samples collected at baseline on participants without cancer in the Atherosclerosis Risk in Communities (ARIC) Study. Over a mean of 17.5 years of follow-up, 668 incident cancers were diagnosed in 2,467 Black participants. Cox proportional hazards regression was used to examine immune cell subtype proportions and overall cancer incidence and site-specific incidence (lung, breast, and prostate cancers). Higher T regulatory cell proportions were associated with higher lung cancer risk (hazard ratio [HR] = 1.22, 95% confidence interval [CI]= 1.06-1.41 per 1% increase in cell proportion) and a borderline increase in overall cancer risk (p=0.06). Increased memory B cell proportions were associated with significantly higher risk of prostate cancer and all cancers (HR=1.17, 95% CI=1.04-1.33 and HR=1.13, 95% CI=1.05-1.22, per 1% increase in cell proportion, respectively). Other immune cell subtypes did not display statistically significant associations with cancer risk in the main analyses. These results in Black participants align closely with prior findings in largely White populations. Our results add to the growing evidence demonstrating the important role of adaptive immunity in cancer risk.