Investigating IL-6-driven inflammation and gene-environment interactions in colorectal cancer disparities among Puerto Rican Hispanics

Early-onset colorectal cancer (EOCRC) is rising in Puerto Rico despite an overall decline in colorectal cancer (CRC) incidence. Interleukin-6 (IL-6), a pro-inflammatory cytokine, has been implicated in CRC progression through inflammatory signaling, immune disruption, and DNA damage. This study explores the association between circulating IL-6 levels and IL-6-related single nucleotide polymorphisms (SNPs) in EOCRC patients to examine if IL-6 contributes to cancer disparities. A case-control design was used with CRC patients (n=20) and healthy controls (n=20). Peripheral blood lymphocytes (PBLs) were collected for DNA extraction and IL-6 real-time PCR genotyping. Plasma IL-6 levels were measured via ELISA. Sociodemographic and lifestyle data were collected through surveys. In our study population, 55.1% had EOCRC, with an average diagnosis age of 51.5 years. A strong family history of CRC was reported by 71.1%. Over 70% of participants were overweight/obese, and 50.7% exercised less than once per week. Pro-inflammatory IL-6 genotypes were more common in individuals under 50 (55.6%) compared to those over 50 (44.4%). IL-6 plasma levels were elevated in controls compared to CRC patients, but differences were not statistically significant. This pilot study reveals a higher prevalence of the pro-inflammatory IL-6 genetic variant among EOCRC. Larger studies are needed to further explore IL-6's role as a contributor of EOCRC disparities. Our findings underscore the importance of fully characterizing non-familial germline genetic variants and their interactions with environmental exposures to fully understand the factors driving EOCRC disparities and to inform targeted risk stratification and prevention strategies.