posted on Thursday, 15th February 2024
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The end is in sight.
Fewer than 25 of our 1879 CaPP3 recruits are now awaiting their
final 60 month follow up visit. We need to have all of
the 60-month visits completed with the data added to MACRO by
30th June 2024. This includes those participants
who withdrew but agreed to follow up and bloods, so that we can
begin the study analysis. Needless to say, the results are
eagerly awaited and will be pivotal in our efforts in the UK to
complete the repurposing of aspirin as a cancer preventive in Lynch
syndrome.
The first two years of the intervention were blinded to capture
a reliable record of adverse events in the three dosage
groups. These data are with Tim Bishop and Faye Elliott, the
study statisticians, for processing and we hope to have this
analysis ready for the summer.
We have been working for five years with colleagues in London,
Boston and Italy as part of the AsCaP programme funded by Cancer
Research UK to explore the way aspirin works. An exciting
piece of research has recently been published by our Italian
partners. They have bred a mouse which has a gene change
making it prone to bowel polyps and has the gene for COX1 out of
action. Aspirin blocks COX1 in platelets, the tiny blood
cells which block small leaks. It also blocks COX2 which is
active in inflammation. For a long time, we have assumed the
main anti-cancer effect is based on blocking COX2. In the
mouse model, stopping COX1 from working suppressed polyp
formation. This supports the idea that activated platelets
expressing COX1 might then trigger the COX2 effect. This is
important because platelets are blocked by small doses of aspirin,
and it would explain why studies involving very low dose aspirin
still show a reduced rate of cancer. If this is the main
effect of aspirin, then we would expect the similar levels of
protection against cancer in all three groups taking part in
CaPP3. On the other hand, if a direct effect on inflammation
is important, then there should be more protection with the bigger
doses.
We are now planning more research into these questions while we
await the final data from CaPP3.
In June I will attend the inaugural Cancer Prevention Conference
in Boston sponsored by Cancer Research UK, the American Cancer
Society and the US National Cancer Institute. I am a co-chair
of the conference alongside Tim Rebbeck from Harvard and Thea Tlsty
from University of California. The plan is that the three-day
conference will bring together the research community around cancer
prevention and stimulate new ideas and studies. It will be in
the UK in 2025 and continue to alternate thereafter. Needless
to say, we will be keen to talk about the CaPP3 results next
year!
John Burn
February 2024
posted on Thursday, 27th October 2022
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CaPPtains Blog - CAPP2 Resistant Starch Update
A diet supplement of resistant starch doesn't reduce colorectal
cancers in Lynch syndrome but does reduce other types of Lynch
syndrome cancer by more than half. This is the important
result from "the other half" of CAPP2, our international research
trial which began more than 20 years ago. It appeared in the
highly regarded research journal, Cancer Prevention Research in
September 2022. It has taken a long time to reach publication
because the result is surprising.
Our CAPP2 trial was double blind, which means no-one knew
whether they were taking the resistant starch or ordinary corn
starch. They mixed 2 sachets with their food each day for
between 2 and 4 years. Some people weren't able to complete
the study, but the effect was so big that the difference was clear
even if the "early dropouts" were included. This is called an
"intention to treat" analysis. The biggest effect was on cancers in
the upper gastrointestinal tract near the stomach and including
cancers in the pipes that let bile out of the liver.
Resistant starch is turned into short chain fatty acids by
bacteria in the gut. The most important of these short chain
fatty acids is butyrate which has been known for a long time to
help reduce cancer. In addition, we think the supplement of
resistant starch may have caused a long-term change in the types of
bacteria in the gut and reduced the production of chemicals called
secondary bile acids which are released in the bile and can cause
genetic damage.
Whatever the reason, the effect on cancer risk is real and it
lasts a long time. There are no important side effects so we
think that everyone with Lynch syndrome should try to increase the
amount of resistant starch in their diet.
The name resistant starch comes from the fact that some starch
is not broken down to glucose in the upper gut. This can be
because they are inside seeds, for example, or because their
chemical structure prevents the digestive enzymes from
working. The best known example is in bananas where the
starch is crystalline but gradually breaks down to glucose as the
banana ripens; hence our advice to eat a green tipped banana a
day. There are lots of other ways to increase resistant
starch. The simple answer is to aim for a "high fibre"
diet.
The important type is resistant starch, also called fermentable
fibre in America because it reaches the bowel bacteria to be broken
down by fermentation. When starches are heated they become
easier to break down in the upper gut. I once suggested that
yesterday's pizza or cold mashed potato would work too which caused
quite a social media flurry!
The take home message is that a high fibre diet is good for you,
reduces cancer risk and can help control your weight because
resistant starch has fewer useful calories. It takes us
nearer to the wild diet eaten by our ancestors.
Speaking of ancestors, the whole CAPP story began when Professor
John Mathers invited me over 30 years ago to speak at a Newcastle
University nutrition seminar where the late great Dennis Burkitt,
who first showed that fibre is good for you, was in the audience. I
think he would approve.
John Burn
October 2022