Aspirin for prevention of colorectal cancer in the elderly: friend or foe?

Abstract

Cancer is the leading cause of death among men and women aged 60-79 years. Colorectal cancer is the third most common cancer in males and the second most common in females, with about 0.8 million deaths worldwide per year. Individuals older than 50 years account for 20-50% of colonic adenomas. Several measures have been proposed to decrease colorectal cancer risks, such as an increase in dietary fiber, use of aspirin, and physical activity. Nonsteroidal anti-inflammatory drugs have been proposed as protective agents against the development of colorectal cancer and colorectal adenomas. Aspirin was the first pharmacological agent endorsed by the United States Preventive Services Task Force screening for colorectal cancer chemoprevention. Although studies have shown up to 40% colorectal cancer risk reduction in individuals at average risk, data regarding this benefit are inconsistent. Several recent studies show that prophylactic use of aspirin in elderly subjects may not be beneficial in preventing the occurrence of colorectal cancers. Given the risks associated with aspirin, such as non-fatal and fatal bleeding events, aspirin's role should be redefined, especially in individuals at risk of bleeding. This review provides a discussion of the recent studies on the role of aspirin use in elderly individuals at risk of colorectal cancer.

Keywords: Aspirin; cancer prevention; chemoprophylaxis; colorectal cancer; elderly.

Figure 1

Schematic illustration of aspirin’s role in colorectal cancer prevention Cyclooxygenase (COX) dependent pathway (Left panel): Inhibition of COX-1 in platelets and COX-2 in epithelial cells. Prostaglandins (PGs) are important derivatives of arachidonic acid. Prostaglandins and thromboxane A2 (TXA2) play a role in platelet aggregation, atherosclerosis, and vasoconstriction. Prostaglandin E2 (PGE2) receptor is involved in cell growth, survival, and proliferation. It is an essential target for hydroxyprostaglandin dehydrogenase (HPDG). COX metabolism also involves gene by environment (GxE), single nucleotide polymorphisms (SNP) rs2920421 and rs2965667, and prostaglandin M (PG-M). COX independent pathway (Right panel): WNT β-catenin is an important target for aspirin by inhibition of protein phosphatase 2A (PP2A). It is also inhibited by the peroxisome proliferator activated receptor (PPAR) induced by the paracrine effect of PGE2. Chromosome 8q24 has an important SNP, rs6983267, which lowers the expression of MYC proto-oncogene via WNT signaling. Furthermore, aspirin mediates its effects via a mitogenic activated protein kinase (MAPK) signaling cascade, nuclear factor kappa beta (NF-kB) and resulting apoptosis (via c-myc and c-fos). Aspirin exerts its anti-inflammatory effects by targeting soluble tumor necrosis factor (TNF) receptor 2 and macrophage inhibitory cytokine (MIC). These actions induce a reduction in the generation of cytokines interleukin (IL) -1 and -6, TNF and chemokines