Cardiovascular Risks Associated With Celecoxib and Rofecoxib Dose/Drugs continued...
A randomized controlled dietary modification study was undertaken among 48,835 postmenopausal women aged 50 to 79 years who were also enrolled in the WHI. The intervention promoted a goal of reducing total fat intake by 20%, while increasing daily intake of vegetables, fruits, and grains. The intervention group accomplished a reduction of fat intake of approximately 10% more than the 8.1 years of follow-up. There was no evidence of reduction in invasive CRCs between the intervention and comparison groups with a HR of 1.08 (95% CI, 0.90–1.29). Likewise, there was no benefit of the low-fat diet on all-cancer mortality, overall mortality, or cardiovascular disease.
Explanations for the conflicting results regarding whether dietary fat or meat intake affects the risk of CRC  include:
- Validity of dietary questionnaires used.
- Differences in the average age of the population studied.
- Variations in methods of meat preparation (in some instances, mutagenic and carcinogenic HCAs could have been released at high temperatures).
- Variability in the consumption of other foods such as vegetables.
In addition, some epidemiological studies have reported lower incidence rates of colon cancer in populations with high intakes of both fat and fiber, compared with populations with high levels of fat but low levels of fiber consumption. Although far from clear-cut, the available evidence suggests CRC risk is possibly associated with some interaction of dietary fat, protein, and caloric intake.
Six case-control studies and two cohort studies have explored potential dietary risk factors for colorectal adenomas.[20,105] Three of the eight studies found that higher fat consumption was associated with increased risk. High fat intake has been found to increase the risk of adenoma recurrence following polypectomy. In a multicenter randomized controlled trial (RCT), a diet low in fat (20% of total calories) and high in fiber, fruits, and vegetables did not reduce the risk of recurrence of colorectal adenomas.
Thus, the evidence is inadequate to determine whether reducing dietary fat and meat would reduce CRC incidence.
A central effect of bile acids in the etiology and pathogenesis of CRC has been claimed. An increased bile acid concentration in the intestinal tract accompanies a high-fat diet because bile acids are released from the gallbladder after fat ingestion. The concentration of bile acids in the colon is heavily influenced by the amount and type of fat in the diet. The potential mechanism of action of bile salts in colorectal carcinogenesis is unknown, although it has been suggested that it is mediated by diacylglycerol. The conversion of dietary phospholipids to diacylglycerol by intestinal bacteria is enhanced by a high-fat diet. It is proposed that diacylglycerol enters the cell directly, stimulating protein kinase C, which is involved in intracellular signal transduction. There is no high quality evidence from either observational studies or RCTs to substantiate this claim.