posted on Wednesday, 17th December 2025
Not tagged.
Permalink
Today the "home team" had our last CaPP meeting before
submitting an amended version of the CaPP3 paper to Lancet
Gastroenterology and Hepatology for consideration for
publication. We originally submitted to Lancet who did not
feel the result was of sufficient general interest and offered
transfer to their specialist subsidiary journal which is,
nevertheless, a world leading journal with a very strong "impact
factor". We are working on our response to the referees'
comments and hope to see the primary report fully published in time
for the meeting in March in Singapore of the International Society
for Gastrointestinal Hereditary Tumours (InSiGHT) where I have the
honour of being an invited speaker.
Today was also an opportunity for Tim Bishop and Faye Elliott to
send their best wishes over Teams to Lynn Reed and Lynne Longstaff
who will be leaving us at the end of the month when the current
CaPP3 grant from Cancer Research UK comes to an end. Lynne
has been with the University for 40 years and became a member of
the CaPP team in 2014. Lynn joined the CaPP team 25 years
ago. They have been vital members of the international CaPP
community and will be greatly missed.
Tim Bishop and I will be leading another funding bid to Cancer
Research UK in the New Year to supplement the recent award by CRUK
of the SPARC programme (suppress platelet activation, reduce
cancer) which I co-lead with Ruth Langley from the MRC until 2029
and which will build on the CaPP biobank. More on this in the
New Year. Fin Macrae has also bid for funds to continue
support of the Australian follow up while we hope the teams in
Finland, Spain and Israel will continue to feed data into the new
REDCap database hosted by our hospital.
As most who read this are already aware, our conclusion from the
data gathered to date is that a "baby" aspirin is as effective at
preventing Lynch cancers as the 600mg dose used in CAPP2.
This involves some complex statistics and, as we predicted, it will
be necessary to continue our follow up to count cancers for a few
more years to finalise the proof. We are particularly
interested to check out the effect of having a higher body
weight. We think people who are significantly overweight will
need extra aspirin. The new guideline of the UK Cancer
Genetics Group will recommend 75mg daily in the UK and 150mg for
those with a BMI over 30. A series of international consensus
meetings of Lynch syndrome experts over the last couple of years
has agreed that people with Lynch syndrome should be advised to
take aspirin and recommends being guided on dose by the CaPP3
result.
New research has identified a chemical in the urine called
thromboxane which is released by platelets. In the
bloodstream, this chemical affects the body's defences against
cancer by making the white blood cells less powerful. Aspirin
suppresses the release of this chemical. In 2026 we will be
inviting all people who took part in CaPP3 to agree to collect a
urine sample at home and send this by mail to Newcastle to add to
our CaPP biobank. We can then begin to link the thromboxane
levels to future cancer risk. This could be a useful test in
the future to decide when to take aspirin and how much is
needed.
For now, thanks again to Lynn and Lynne for their many years of
service and Seasons Greetings to all who support our Cancer
Prevention Programme.
John Burn
An interview from the CGA conference in St Louis after I
presented the CaPP3 results:
https://www.youtube.com/watch?v=oexnbYBZrlw
Keynote Session - Should I Take an Aspirin? Aspirin
Chemoprevention in Lynch Syndrome - 2nd Annual Lynch
Syndrome Scientific Symposium, Daner-Farber Cancer Institute,
Boston:
https://www.youtube.com/watch?v=dwufGCxoPlQ&list=PLPLXayOtubE3TnXOKMLpNBa1CTAFLB06y&index=5
posted on Thursday, 15th February 2024
Not tagged.
Permalink
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