Changes in serum lipids related to the presence of experimental colon cancer

Abstract

Summary People at risk from coronary heart disease and large bowel cancer are drawn from the same urbanised, industrialised Western populations. Whilst changes in blood lipids are well recognised in heart disease, little is known of their role in large bowel cancer. This study investigates serial alterations in blood lipids in the 1,2-dimethylhydrazine (DMH) rat model of colon cancer. Eighty Wistar rats received a 5 weekly regimen of DMH. At week 10, and at 5 weekly intervals until week 40, random groups of 10 rats were killed and blood taken for total and free cholesterol, phospholipids, triglycerides and liver enzymes. All colonic neoplasms were histologically classified either as adenomas or carcinomas with groups being allocated into tumour-free (n = 16) or tumour-bearing (n = 54), the latter group being further sub-divided into animals with adenoma alone (n =8) and those with carcinoma (n = 46). Results were considered both sequentially and according to tumour status. Sequential results showed that with increase in colonic neoplasms with time there were accompanying increases in free and % free cholesterol and in phospholipids (P<0.001). There were no changes in total cholesterol, triglycerides or liver enzymes. Results according to tumour status showed that whilst there was no difference in total cholesterol or triglycerides between tumour-free and tumour-bearing rats, there was a significant increase in free (P<0.01) and % free cholesterol (P<0.001) and a decrease in phospholipids in the tumour-bearing animals (P<0.001). There was no difference in any serum lipid between tumour-free and adenoma-bearing rats. In animals with carcinoma, while there was no difference in total cholesterol or triglycerides, there was an increase in free (P<0.005) and % free cholesterol (P<0.001) and a decrease in phospholipids (P<0.001) compared to tumour-free rats.The data show for the first time a clear relationship between blood lipids and the presence or absence of large bowel cancer.The incidence and mortality rates for large bowel cancer are the second highest of all malignant disease in Western society (American Cancer Society, 1978). Although the cause(s) of colon cancer is unknown, epidemiological studies have implicated dietary fats in the pathogenesis of this disease (Wynder, 1975;Doll, 1978;Wynder & Reddy, 1983). More specifically, cholesterol in the diet has been shown to be co-carcinogenic in animals (Cruse et al., 1978(Cruse et al., ,1982 and there is indirect evidence for a similar role in man (Cruse et al., 1979;Broitman, 1981).Populations at high risk for colorectal cancer (CRC) are similarly at high risk of coronary heart disease (CHD) (Hill, 1975;Wynder & Shigematsu, 1967) and a common factor for both diseases is the high fat intake of the 'at risk' population (Hill, 1975). The familiar direct relationship between serum cholesterol levels and CHD probably reflects a causal role between hypercholesterolaemia and atherosclerosis (Lewis, 1983). Recent evidence also indicates that a direct but inverse relation...

Hypertriglyceridemia is positively correlated with the development of colorectal tubular adenoma in Japanese men

“…This suggests overlapping mechanisms that increase the risk of colon cancer and hyperlipidemia. On the contrary, other reports failed to detect a significant association between serum levels of triglyceride as well as cholesterol and risk of colorectal cancer in human [16,17] and animal studies [18] . Thus, the true association between circulating lipid levels and colonic neoplasm development has not been satisfactorily determined in humans.…”

Concurrent suppression of hyperlipidemia and intestinal polyp formation by NO-1886, increasing lipoprotein lipase activity in Min mice

“…At present, it still cannot be stated with certainty whether hyperlipidemia is a leading cause of intestinal polyp formation. Colon tumors induced by 1,2-dimethylhydrazine in rats, however, are not linked to serum lipid levels (19). As hyperlipidemia and polyp formation could be related to Apc-deficiency independently, we now address whether low LPL activity and high serum lipid levels could promote intestinal polyp formation in these mice.…”

Silibinin alleviates hyperlipidaemia, restores mucin content, modulates TGF-β and fosters apoptosis in experimental rat colon carcinogenesis

“…The findings of the present study showed a significant increase in the levels of serum lipid profile other than HDL demonstrating a hyperlipidaemic state that is associated with massive tumour burden in DMH alone administered rats. In contrast it has been reported that there are no notable changes in serum triglycerides and total cholesterol in rats with colon tumours induced by 1,2-dimethylhydrazine though there was an increased tumour burden (Barton, Cruse, & Lewin, 1987). Hence it can be speculated that high dietary fat played a remarkable role in eliciting hyperlipidaemia in the DMH model.…”