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 APC
MIN, 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.
