Friday, June 8, 2012

Eating Healthy; One of the Best Treatments for Genetic Predispositions to Adenocarcinomas

I came across a study rather similar to one of the examples Dr. Chernikova shared with us in her lecture; the one concerning the effects of a healthy diet on breast cancer occurrence in mice. There are, however, a two key difference between the study Dr. Cherikova bright up and this study, done by Dr. Volker Mai. First, instead of correlating dietary habits in mice to breast cancer, Mai looked into adenocarcinomas of the gastrointestinal track. Second, all of the mice within this study were bred to be carriers of APCMIN, which give them the mouse equivalent of Familial Adenomatous Polyposis (FAP). I wrote early on FAP, but the short story is that, in humans, its genetic disorder that results in hundreds to thousands of polyps in the colon and intestines due to a mutation in the APC gene that leads to over-expression of the WNT pathway.

Mai tested mice within four treatment conditions. Aside from the control group which was fed normal pellets, one group was given a diet with a calorie restriction 40% below the control, one was given a high fat diet, and the last a diet high in olive oil and supplemented with freeze-dried fruits and vegetable extracts with a total calorie count similar to that of the high fat diet. After nine weeks on the diets, necropsies were performed on all the mice. The results are nicely summarized below in Figure 1.

Figure 1. Mean (± SE) polyp numbers in ApcMin mice after 9 weeks of dietary treatment. Total polyps (▪), total polyps > 2 mm (□), colon polyps (▨). Control (n = 30); Calorie-restricted (CR) [n= 28; P versus control (total polyps) <0.0001]; Supplemented (OFV) [n = 30; P versus control (total polyps) = 0.04]; and High fat (HF) = high corn oil [n = 14; P versus control (total polyps) = 0.5].

As you can see above, there are significant differences in the numbers of total polyps (black bars) per mouse in each treatment group. The calorie restricted (CR) diet and the supplemented diet (OFV) obviously both resulted in notably lower average polyp counts than the control and high fat (HF) diets. This trend hold when the count is restricted only to polyps greater than 2mm in length, though the relative range has decreased notably. Once restricted to solely colon polyps, the results become too close to be considered significant.

Ignoring the colon-specific results, diet appears to be a firm factor in the formation of adenomas. The 40% restricted diet resulted in 57% fewer polyps on average relative to the control (P < 0.05). It's important to note that this reduction was not great enough to result in malnutrition. This large of a contrast is rather self explanatory. If these results hold true in follow up studies and carry over to humans, then calorie restriction definitely a viable means of deterring polyp formation in carriers of Familial Adenomatous Polyposis (FAP) and very possibly the numerous other genetic disorders characterized by increased risk of adenocarcinoma.

The high fat (HF) diet, while having accrued the highest average number of polyps, was not significantly larger than the control (P = 0.5). The supplemented diet (OVF), however, resulted in 33% fewer polyps on average (P = 0.04), which marks it as another viable dietary option in deterring polyp formation. With the supplimented diet, however, the best comparison that can be made is to the high fat diet as it as the overall calorieintake, food mass and % kilocalories from fat are close in both these treatments, the difference in polyp count can be attributed to the nutritional difference between the two diets. No r-value is available for this comparison, but there does seem to be a significant difference between the two diets. This suggests that in lieu of calorie restriction, people partaking of a high fat diet can simply change the contents of their diet without having to restrict calories and deter polyp formation to a significant degree.

The fact that these mice carry the equivalent of Familial Adenomatous Polyposis in humans makes the result especially promising. Given the sheer quantity in which polyps form in the colon and intestines of these patients, a 33-57% decrease in polyps can easily equate to thousands of prevented polyps over a lifetime. Such a deterrent could easily grant these patients years of additional time before the disease either overwhelms them or they're forced to undergo a colectomy (removal of the colon) as is commonly the case and results in numerous digestion complications. Furthermore, calorie-restricted and nutritionally-supplemented diets are relatively cheap means of preventing polyp formation.

Despite the strength of the overall results, personally, I initially found these results rather disappointing. As my topic revolves around andenocarcinoma of the colon, it was frustrating to find such clear distinctive results from the total polyp count while the results from only the colon came out to be statistically insignificant. The problem is how low the average number of colon polyps per mouse is. With each treatment group containing only 14-15 mice and the average colon polyp count in each group landing well below 0.5 polyps per mouse, significant results would be nigh impossible to achieve.

In addition to a larger test group, the study would have needed to extend beyond nine weeks in order to allow colon polyps more time to form and grow. Unfortunately, this probably isn't a viable option. Given how aggressively polyps formed within the small intestine during these nine weeks, any significant increase in the length of the experiment would probably prove sufficiently long enough for the polyps in the small intestine to kill off a significant number of mice in the control and high fat diet treatment groups. Possibly, by using a different animal model, significant results on the colon alone could be produced. However, despite the statistically insignificance of the colon-only data, the functionality of the formation of adenocarcinoma in the small intestines is highly comparable to that of the large intestines, so the the overall results are at least indicative of a possible trend in the colon as well.