The Role of Dyslipidemia in Colitis-Associated Colorectal Cancer

Abstract

Dyslipidemia, characterized by metabolic abnormalities, has become an important participant in colorectal cancer (CRC). Dyslipidemia aggravates intestinal inflammation, destroys the protective mucous layer, and disrupts the balance between injury and recovery. On the other hand, antioxidants induced by oxidative stress enhance glycolysis to maintain the acquisition of ATP allowing epithelial cells with damaged genomes to survive. In the repetitive phase of colitis, survival factors enable these epithelial cells to continuously proliferate. The main purpose is to restore and rebuild damaged mucosa, mainly aiming to recover mucosal damage and reconstruct mucosa, but it is also implicated in the occurrence and malignancy of CRC. The metabolic reprogramming of aerobic glycolysis and lipid synthesis enables these transformed epithelial cells to convert raw carbohydrate and amino acid substrates, thereby synthesizing protein and phospholipid biomass. Stearoyl-CoA desaturase, responsible for the fatty acid desaturation, improves the fluidity and permeability of cell membranes, which is one of the key factors affecting metabolic rate. In response to available fat, tumor cells reprogram their metabolism to better plunder energy-rich lipids and rapidly scavenge these lipids through continuous proliferation. However, lipid metabolic disorders inhibit the function of immune-infiltrating cells in the tumor microenvironment through the cross-talk between tumor cells and immunosuppressive stromal cells, thereby providing opportunities for tumor progress. Nonsteroidal anti-inflammatory drugs and lipid-lowering drugs can decrease the formation of aberrant crypt foci, lower the burden of the adenomatous polyp, and reduce the incidence of CRC. This review provides a comprehensive understanding of dyslipidemia on tumorigenesis and tumor progression and a development prospect of lipid disorders on tumor immunity.

Dyslipidaemia Is Associated with Severe Disease Activity and Poor Prognosis in Ulcerative Colitis: A Retrospective Cohort Study in China

“…Consistent with a previous study [ 15 ], our work also showed that dyslipidaemia played a role in the incidence of tumorigenesis associated with colitis. Regarding the mechanism, dyslipidaemia has been validated to prolong the disease course and increase cumulative genetic mutations in the intestinal mucosa, leading to an increased risk of tumorigenesis [ 2 ].…”

“…It has been reported that serum lipid profiles differ not only in Eastern and Western populations [ 7 , 8 , 9 , 10 ] but also in patients with UC and the general population [ 11 , 12 ]. Remarkably, previous studies have demonstrated that serum lipid abnormalities not only aggravate disease activity in UC [ 2 , 13 ] but are also associated with an increased likelihood of surgery [ 14 ] and tumours [ 15 ] among patients with IBD, revealing a potential role of dyslipidaemia in inflammation and disease progression. However, only a few studies have assessed the association between lipid profiles and morbidity [ 16 ] and disease activity [ 13 ] of UC, and they had small sample sizes and inconsistent results.…”

High Levels Of Triglycerides And Apolipoprotein B Increase The Risk Of Colorectal Polyp Recurrence After Endoscopic Resection

“…To our knowledge, this is the rst report linking high apoB to polyp recurrence. Our ndings are consistent with studies suggesting that hypertriglyceridemia promotes the formation of reactive oxygen species that damage DNA and thereby initiate CRC 23 , and that this and other abnormalities of lipid metabolism suppress anti-tumor immune responses 14 .…”

“…Elevated triglyceride levels in serum are an independent risk factor for polyp recurrence in patients with advanced adenomas 13 . Long-term lipid stimulation suppresses anti-tumor immune responses, facilitating colorectal tumorigenesis and distant metastasis, and suppresses immune in ltrating cell function in the tumor microenvironment, thereby accelerating tumor progression 14 . On the other hand, several studies have suggested no association or negative correlation between lipid levels in blood and risk of colorectal polyps or CRC [15][16][17][18][19][20] .…”

The predictive value of routine laboratory tests for colorectal polyps: a retrospective study

“…Although there was no significant difference in TC (P=0.227) and TG (P=0.11) levels in our study, we found that LHR was an independent predictor of colorectal polyps, which indirectly reflected the relationship between dyslipidemia and colorectal polyps. A possible explanation is that dyslipidemia strengthens the inflammatory response and accelerates injury to the mucosal epithelium, which has a great influence on the occurrence of tumors (35).…”