Chronic inflammation of the colon, especially in seniors, can lead to colon cancer through a complex interplay of immune responses, cellular damage, and changes in the tissue environment that promote tumor development. This process unfolds over many years, often beginning with persistent inflammation caused by conditions like ulcerative colitis or Crohn’s disease, which are types of chronic inflammatory colitis common in older adults.
When the colon is chronically inflamed, the immune system is continuously activated to repair tissue damage. This ongoing immune response involves immune cells such as macrophages, neutrophils, and lymphocytes releasing a variety of inflammatory molecules including cytokines, chemokines, reactive oxygen species (ROS), and nitric oxide. These substances, while intended to heal, can inadvertently damage the DNA of colon cells. DNA damage leads to genetic mutations, which are critical steps toward the transformation of normal cells into cancerous ones.
Macrophages, particularly tumor-associated macrophages (TAMs), play a pivotal role in this process. In the inflamed colon, TAMs can adopt a phenotype that supports tumor growth by producing enzymes like matrix metalloproteinases (MMPs) that remodel the tissue and facilitate cancer cell invasion. They also secrete growth factors such as epidermal growth factor (EGF) and inflammatory cytokines like IL-6 and IL-1α, which stimulate cancer cell proliferation and survival. This creates a microenvironment that favors tumor initiation and progression.
Chronic inflammation also activates key signaling pathways inside cells, including nuclear factor kappa-B (NF-κB) and signal transducer and activator of transcription 3 (STAT3). These pathways promote the expression of genes that encourage cell survival, proliferation, and angiogenesis—the formation of new blood vessels—which tumors need to grow and spread. The inflammatory environment can suppress the immune system’s ability to detect and destroy emerging cancer cells, allowing these mutated cells to evade immune surveillance.
In seniors, the risk is compounded by age-related changes in immune function and tissue repair mechanisms. Aging can impair the immune system’s efficiency, reducing its capacity to clear damaged or abnormal cells. Additionally, the cumulative exposure to inflammatory insults over time increases the likelihood of genetic mutations and epigenetic changes that drive cancer development.
The chronic inflammatory state also promotes epithelial-mesenchymal transition (EMT), a process where colon epithelial cells gain migratory and invasive properties, facilitating cancer metastasis. TAMs contribute to EMT by producing factors like transforming growth factor-beta (TGF-β) and MMPs, which break down the extracellular matrix and allow cancer cells to invade surrounding tissues.
Furthermore, chronic inflammation induces metabolic changes in colon cells, including mitochondrial dysfunction and increased production of ROS. Elevated ROS levels cause oxidative stress, further damaging DNA and cellular components, which accelerates carcinogenesis.
In summary, chronic inflammation in the colon leads to cancer in seniors through a multifaceted mechanism involving DNA damage from inflammatory mediators, promotion of tumor-supportive immune cells, activation of oncogenic signaling pathways, suppression of anti-tumor immunity, stimulation of angiogenesis, and facilitation of cancer cell invasion and metastasis. The aging immune system’s diminished capacity to control these processes makes seniors particularly vulnerable to inflammation-driven colon cancer.