Exploring the genotoxic and tumorigenic potential of artificial food dyes and implications for colorectal cancer risk in socioeconomically disadvantaged communities.

Abstract

e22580 Background: The artificial food dyes Blue No. 1, Blue No. 2, and Red 40 are common in processed foods and have been increasingly scrutinized for their potential biological effects. Experimental evidence links these dyes to DNA damage, immune dysregulation, and colonic inflammation, raising concerns about their possible role in cancer-related pathways despite regulated safety thresholds. Exposure is disproportionately higher in socioeconomically disadvantaged communities due to reliance on ultra-processed foods, food deserts, and constraints within nutrition assistance programs like SNAP. As early-onset colorectal cancer incidence rises, these populations face uneven burdens. Chronic dietary exposure to synthetic dyes may influence colorectal tumorigenesis through inflammatory signaling and PANX1-mediated immune responses. This study synthesizes current evidence on artificial food dyes and nutritional inequity to evaluate their potential contribution to EOCRC risk in vulnerable groups. Methods: A narrative literature review was conducted using peer-reviewed studies and regulatory reports from PubMed, NIH-affiliated databases, major scientific journals, and federal agencies, with findings synthesized qualitatively to assess biological pathways and EOCRC disparities related to Blue No. 1, Blue No. 2, and Red 40. Results: Across peer-reviewed studies, Blue No. 1, Blue No. 2, and Red 40 were associated with biological processes relevant to colorectal carcinogenesis. Blue No. 1 showed genotoxic effects in human lymphocytes, including DNA strand breaks, an early event in colorectal tumorigenesis. Blue No. 2 exposure was linked to tumor formation under certain experimental conditions and caused reproductive toxicity and tissue disruption in animal models, suggesting dysregulated cellular repair pathways. Pannexin-1 (PANX1) hemichannel activity promoted colonic inflammation, pathogenic CD4⁺ T-cell responses, and tumor progression, with elevated PANX1 expression associated with worse survival in colon cancer patients. Although Blue No. 1 inhibits PANX1 activity, its broader genotoxic effects suggest multiple, potentially opposing biological interactions. Red 40 consistently exacerbated colitis and immune-mediated intestinal inflammation through microbiome-dependent pathways and pro-inflammatory cytokine signaling. Population-level studies showed that low-income and SNAP-participating populations consume more ultra-processed foods and experience worse EOCRC outcomes, highlighting structural exposure risks. Conclusions: Synthetic food dyes may contribute to EOCRC through genotoxic, inflammatory, and immune-signaling pathways. Structural inequities increase exposure in low-income communities, highlighting the need for human based studies to clarify risks and guide policy.