Cancer and Obesity: Understanding the Connection

Key Takeaways

Links Between Obesity and Cancer
Obesity is associated with increased risk and altered outcomes across several cancer types, including colorectal, melanoma, and thyroid cancers. Mechanistic pathways link excess adiposity to cancer hallmarks such as chronic inflammation, metabolic dysfunction, and hormonal disruption. Early-life excess weight development may influence future cancer risk through intermediate biological changes.

Childhood Obesity and Cancer Risk
Higher BMI in childhood is linked to an increased risk of developing obesity-related cancers later in life, particularly among women. Risk increases with greater severity of obesity. Current prevention strategies targeting childhood obesity are often limited in reach, intensity, and long-term impact.

Impact of Obesity on Cancer Outcomes
Obesity influences cancer prognosis, treatment planning, and screening participation. Individuals with obesity are more likely to experience dose capping during chemotherapy and reduced uptake of screening. Some inverse associations between obesity and cancer outcomes may reflect reverse causation or confounding. Screening protocols may require adjustment for populations with obesity-related conditions such as type 2 diabetes.

Melanoma and Thyroid Cancer Considerations
Associations between obesity and melanoma remain inconsistent and may vary by population characteristics and study design. Incidence of young-onset thyroid and colon cancers appears to be rising and may present more aggressively.

Data and Communication Considerations
Limited availability of historical body composition data constrains long-term research on obesity and cancer. Person-first, inclusive, and non-stigmatising communication should be embedded across research activities to support meaningful engagement and avoid harm, particularly in studies involving children and young people.

Future Directions and Next Steps

• Prioritise cohort studies using body composition data to explore associations with cancer risk, progression, and long-term outcomes
• Investigate how higher body weight in childhood may relate to early-onset and more aggressive forms of cancer later in life
• Examine how medications used in obesity management (e.g. GLP-1 receptor agonists) may influence cancer risk and outcomes
• Strengthen inclusion of people living with obesity in oncology trials and apply stratified analyses to improve relevance and equity
• Embed non-stigmatising, person-centred principles across all stages of cancer and obesity research, from design to dissemination

Transcripts are auto generated, if you spot an error, please email enquiries@easo.org

Speaker 1
00:00 – 03:26
Hello to everybody. I am Luca Bugetto. I am the Vice President of the European Association for the Study of Obesity for Southern Europe. And today I will be the chair of this very nice IESO COMMS webinar dedicated to understanding the connection between obesity and cancer. a very hot topic and a very interesting one. Welcome to this webinar and thanks for joining this webinar. The webinar topic is about the relationship between obesity and cancer. I am sure that you will learn a lot for this webinar because we have very two distinguished speakers today. The speakers will be Jennifer Baker and Andrew Rinehan. I will introduce them much more in detail later. I need to inform you that the webinar is recorded. And recording and any relevant resource will be available in the IESO video archive soon after the session. This webinar is part of the monthly COMS webinars that have helped to share knowledge and expertise across the EASOCOMS network to enhance obesity management and patient care. And please encourage your colleagues to share the webinars and to attend the webinars also in the future. You will have the opportunity to ask questions. Please do this through the chat. We will address the question in the last 15 minutes of the webinar. It is also important for you to complete the anonymous feedback form that you will receive and emphasize and what is valuable for you, also for letting us to improve our future webinars structure. I will use maybe one minute more before starting to remember to you some important events that IESO will organize this year. In particular, I would stress the IESO COMS Summit 2025 that will be held in Paris in the first and second day of December this year. You will receive much more detail in the future and you will also have information on the EASOCOM’s websites. Of course, remembering that the last European Congress of obesity that we had in May, a very nice Congress with a lot of attendees and a lot of science inside, I wish to invite you to start to think in your participation at the next European Congress on Obesity that we have

Speaker 2
03:26 – 03:26
in

Speaker 1
03:26 – 04:12
Istanbul, in Turkey, on 12-15 May 2026. This is a lot of things, so I think that IESO is doing the best for you for improving obesity science and management in Europe and also outside Europe. So I think now that we can move to the content of the webinar. We will have two talk. The first talk, the title of the first talk is “Obesity and Cancer, Understanding the Evidence.” And the speaker will be Jennifer Becker. Jennifer is IESO President

Speaker 2
04:12 – 04:13
-elect

Speaker 1
04:14 – 05:02
and Head of Life Course Epidemiology Center for Clinical Research and Prevention in Copenhagen University in Denmark. Is internationally, she is internationally recognized for her work on the long-term association between obesity and health in general. And in the today talk, Dr. Baker, Jen, will explore the evidence linking obesity and cancer risk across different cancer types, highlighting the key findings for life course research. So Jennifer, I think that we can start with your talk. The floor is yours. And thank you for participating in this event.

Speaker 3
05:04 – 05:19
Wonderful. Thank you, Luca. So I am attempting to share my screen. It’s always the most exciting part of a talk on Zoom. And are you seeing the proper screen or the notes screen?

Speaker 1
05:22 – 05:24
– Not in the full screen yet, Jennifer.

Speaker 3
05:25 – 05:26
– Not in full screen yet. Indeed,

Speaker 1
05:26 – 05:27
this is exciting.

Speaker 3
05:30 – 05:33
Is it there now? We just practiced a minute

Speaker 2
05:33 – 05:34
ago. – Yes, it was.

Speaker 3
05:35 – 06:52
– Excellent. Wonderful, wonderful. Thank you again for the opportunity to be here today and to share with you about obesity and cancer. In terms of conflict of interest, I have no conflicts of interest with regards to this presentation, but I have received consulting fees from Novo Nordisk AS. So as a reminder to always set the stage, it’s important how we speak about and show obesity. Obesity is a disease per international definitions. People-first language applies to obesity. This is standard practice for other diseases. We say people with diabetes, not diabetics, for example. So this is how we should talk about obesity as well. And it’s also incredibly important that we use positive imagery for obesity. And just as a reminder, free resources exist and here’s the website for that. So the topic of today is incredibly important and timely. It’s the links between obesity and cancer. As a reminder, overweight and obesity are medical conditions marked by an abnormal and/or excessive accumulation of body fat that presents a risk to health. What we see here in the circle is a perfectly healthy adipocyte. This is the fundamental unit that leads to obesity.

Speaker 4
06:54 – 06:54
– A lovely one.

Speaker 3
06:54 – 22:52
– A good one. When it comes to cancer, this occurs when body cells grow uncontrollably and spread to other parts of the body. In the circle, you see the number 200. I have that there because there are more than 200 forms of cancer. It’s such a simple word for such a complex disease. And today we’re gonna explore the evidence linking obesity with cancer. If we consider the landscape of overweight and obesity in Europe, it turns out that one in two adults are living with overweight or obesity. If we dial the clock back and look into children and adolescents, it turns out that one in three are living with overweight or obesity. This is not a small public health challenge. It’s also a challenge for the individuals. If we look at the landscape of cancer in Europe, it turns out that one in three individuals in Europe will have cancer before the age of 75 years. So again, another incredible personal and public health challenge. And we’re here today because when we put this picture together, you can see that an immense number of individuals will be affected. Now the links between obesity and cancer, they’re not just here in a map, they’re not They exist. What we see here are the hallmarks of cancer and the progressing factors for cancer. So in cancer, the cells become incredibly efficient at evading growth suppressors, avoiding immune destruction. They become good at inducing angiogenesis and so on. This is a really incredibly central figure to cancer research. If we tie obesity into this, Obesity has a role in deregulating cellular energetics, thus providing a mechanistic link between the two. Furthermore, hyperinsulinemia, which goes along with obesity, it ties into sustaining proliferative signaling, again, another mechanistic link to cancer. Furthermore, there’s altered macrophage function in obesity, which ties into avoiding immune destruction. Inflammation to tumor-promoting inflammation, adipostromal cells going into inducing angiogenesis. And furthermore, there’s reduced apoptosis, which again ties into resisting cell death and providing this mechanistic link to cancer. When it comes to the landscape for the links between adult obesity and cancer, they’re quite well-established. There’s two really key organizations. One is the International Agency for the Research on Cancer, which is part of the WHO. And the other one is the World Cancer Research Fund. Both of these bodies have been incredibly busy working across decades, really trying to show the scientific evidence linking adult obesity to cancer. So in about 2016, a group of us were convened in Lyon in France, and Andrew was there as well. So it’s a real pleasure to share this session with him today, Professor Andrew Ranahan, that is. And this picture is actually us standing on the steps. I wish that I could show you the picture from the handbook that we created at this event, but the difficulty is the picture on the cover is quite stigmatizing, so I choose not to show it anymore. Times have passed and things moved on. So again, positive imagery is incredibly important. And another really key report is by the World Cancer Research Fund. Again, they comb through the evidence so that we don’t have to. The totality of what this has really shown is that there’s well-established links between adult obesity and 13 forms of cancer illustrated here in this graphic. Undoubtedly, there are more links, but at the time these reviews were conducted and they take an incredible amount of time, effort and money, these additional forms weren’t so strongly supported by the evidence, but I think as time goes on, we will see these additional forms. Now, this is the landscape for adult obesity and cancer. There’s no questions asked, But you know, if we think back to that map I showed you, we know that one in three children and adolescents are living with overweight and obesity. So as a life course epidemiologist, this really to me begs the question, what about body size earlier in life and cancer? Are there potential mechanisms linking these two together? Well, indeed there are. Childhood is a time of rapid cellular division and there’s an increased opportunity for cellular damage. This is incredibly germane to what we think about cancer because there can be many, many years, even decades between the initial mutation and the clinical detection of a cancer. There’s certainly hormonal exposures during this period of growth. Additionally, there’s exposure to classic carcinogens as these children become adolescents. And furthermore, childhood is a period of long bone growth And there are thoughts that insulin-like growth factor one, which relates to bone, also relates to an increased risk of cancer. So there are plausible mechanisms. Over the past, I dare say decades, we’ve been doing work in this area using the Copenhagen School Health Records Register. Because if we want to know how childhood body size relates to cancer, fortunately cancer has an increasing incidence at later adult ages, we need to turn to more historic records because the individuals do need to become old enough to unfortunately experience cancer for us to be able to study the topic. In the register that we use, there’s 406,350 boys and girls, but the really key part is they’ve been born from 1930 to 1996. They are measured in school, just like we see this nurse here measuring this boy. They had their heights and weights measured from seven to 13 years of age. And the really key thing is this is a population-based cohort, it includes virtually all school children in Copenhagen. And of course, the really key point is this information has been computerized and we are adding additional years and we’ve moved on in technology. So we’re doing machine reading the records, but within these records, each child has an individual identification number issued by the Danish government. So this allows us a one-to-one linkage with a variety of registers. And it just so happens, we have an incredibly world-renowned cancer register. And this has really been the fundamental basis for most of our work. So today I’m gonna share just a few results. First, I’m gonna give you a broad overview of our work. Then I’m gonna talk a little bit about growth trajectories. And then I’m gonna really dial in to colorectal cancer. So when we look at BMI and cancer, what I have here is a graph on the X-axis as the Hadza ratio. If we see the estimate lying to the left of the line, it means that a higher BMI in childhood decreases the risk of cancer. If the estimate lies to the right, it means higher the BMI, higher the risk of cancer. So as you might expect, and this is what we found, that when it comes to cancer forms, especially the ones which are obesity-related as highlighted here, plus a few others, We typically find the higher the BMI in childhood, the higher the risk of cancer. These risks are incredibly pronounced for those of the endometrium and ovary, and this aligns very closely to what’s seen in adults. But nonetheless, BMI in childhood is not related to all forms of cancer, and we find no findings for glioma or brain cancer, melanoma or skin cancer, and rectal cancer. Then we do have the one outline finding that the higher the BMI in childhood, the higher the risk of breast cancer. This is actually well-known, it’s been replicated in numerous cohorts, and there’s some really good fundamental biological reasons for this. I’m happy to explain further, but I’m not gonna go closer into this today. Instead, what I’m gonna do is take a look at, with this research I’m showing in front of you, this is typically a BMI, body mass index at a single age. What we were asking ourselves is a single age enough, should we capture the full trajectory of growth across childhood? And indeed, this is what I’m gonna show you in our next study. So what we did was we grouped all of those obesity-related cancers, the ones I’ve highlighted here in red, according to the IRC and WHO, and we performed a study. So what we did, we looked at how BMI in childhood related to all obesity-related cancers, thinking there’s similar mechanistic links between the two. Again, we use children of the Copenhagen School Health Records Register. These children were born from 1930 to 1988. We needed them to be old enough to enter into the study. And we linked to a variety of registers. What we did was we used latent class trajectory modeling to really create patterns of growth, the totality of the children’s growth across childhood. So on the x-axis is age, on the y-axis is body mass index. And you can see children fell into five classes in these data, which we termed anything from below average up to the class of obesity. I should say in our data, we don’t have nearly as many children in the obesity class because these are historical records, but nonetheless, we still do have children in that trajectory. So what we did, we looked at the data, we made our linkages, And it turned out we had more than 7,200 cases in men and more than 702,000 cases of these cancers in women. So what I have here is our final results from this project. On the X-axis is the childhood BMI trajectory. And in this case, we’re gonna compare everything back to average. On the X-axis is the incidence rate ratio. So if the estimate lies above the dotted line, it means there’s an increased risk. And if it’s below, it means there’s decreased risk. we perform this analysis separately for men and women. Women are in the circles and men are in the squares. And when we do this, a clear pattern emerges. We can see that for below average, the estimates, although not always statistically significant particularly for the women, they tended to fall below the line, saying that a below average BMI is somewhat protective against obesity-related cancer. And again, compared to average, the above average trajectory, we can see the estimates were a little bit above, only statistically significant in women, but we’re looking at the total pattern here. But by the time we reach the overweight and obesity trajectories, we can really see that children in these trajectories had a much higher risk of having obesity-related cancer in adulthood. So this is the total picture of what we’re finding. And if we think about this and apply it to contemporary populations today, this does not paint a good picture for future health. Now, as I said, this is a broad stroke, you know, everything’s put together. So what does it look like if we dial into just one form of cancer? So I’m gonna end my talk today with a little bit deeper dive into colon cancer. Now, again, we’ve already seen that BMI in childhood is associated with an increased risk. Well, what I’m gonna show you is what this really means. So if we think for a second or two about colon cancer, it’s the third most common cancer form in Europe. The five-year survival rate is greater than 90% in many countries. The incidence increases from age 50 years, but we do know, and perhaps you’ve heard of the media, that rates are rising in the under 50s. So what we have here on the right is a map of Europe and the age standardized rates. The darker the color, the higher the rates. That’s not good. And we can see where we are in Denmark. We’re actually amongst some of the highest. So this is a really common form of cancer. it’s really important to understand there’s something we can do to help prevention earlier in life. And if we do consider colon cancer risk factors, they are the typical array of what we expect when we talk about cancer. There’s some we can modify, some we can’t. As for example, family history, you can’t change it. Age, you can’t change it. But when it comes to alcohol, smoking, physical activity and dietary factors, those are modifiable, as is adiposity. In this particular study, again, we used the school health records, we used a different subset of the data because we needed the individuals to be of age 40. It was just a way we did the data because colon cancer, fortunately, is quite rare below 40. So, what we see here in this particular study was an older study. We only had 2,676 cases in women and men, but what we were able to do was look at BMI individual ages. So this is the data underlying that graphic I showed you a few minutes ago. On the x-axis we have age, on the y-axis we have the hazard ratio. And again, an estimate above the dotted line means the higher the BMI, the higher the risk, or below means the higher the BMI, the lower the risk. And really what we see at any age between 7, 10, or 13 years of age, the higher the BMI, the higher the risk. These point estimates mean the associations are linear. So how do we put this into perspective? If we consider an average height boy, but one who weighs 5.5 kilograms more, the boy who weighs that amount more has a 9% increased risk. So we aren’t talking about really large amounts of excess weight, we’re talking about these small amounts which translate to this increase in risk. Now, right now, as I mentioned, BMI and colon cancer risk is really in focus in the media. It’s also an important priority of the World Cancer Research Fund. The World Cancer Research Fund has a flagship program. In this research program, which is called the Global Cancer Update, they go through the literature on a continuous basis, and they really go through and examine what strength of evidence do we have that this factor is related to cancer with a large focus on prevention. So what we just completed, I was fortunate part of the project, where they reviewed the literature on childhood BMI, adolescent BMI and young adult BMI, and they came up with a grading of the evidence as strong probable. In World Cancer Research Fund terminology, this is the highest evidence possible. So it means the higher the BMI, any of these early life periods, the higher the risk of colon cancer. But really the thing that’s good about this is, it does mean there’s potential for prevention. And with that, I will end up with some key takeaways. Obesity is a gateway disease to cancer. These risks increase at levels below obesity, in many cases as a continuous increase. And we can see that obesity already in early life indicates risks for adult cancer. So I think the key message really is, and I really look forward to hearing Professor Renehan’s talk, that prevention, treatment, and management of obesity at all life stages is essential to prevent many cancer forms. And with that, I will say thank you for your attention, my funding for these studies, and of course to my wonderful collaborators. Thank you.

Speaker 1
22:54 – 24:31
>> Thank you, Jennifer. Thank you for this very interesting talk. And then thank you for your last sentence, emphasizing the need for intervention early in life in order to prevent this complication in particular. But in general, we can extend this concept to all the complications of obesity indeed. I remember to the attendees the possibility to ask question through the chat function of the Zoom. We will have a discussion about question at the end of the meeting. And then I will move to the second talk for today. The title of the talk is Clinical Management Issues in Patients Living with Obesity. and cancer. And I am very happy today to have as a speaker, Professor Andrew Renehan. Andrew is Professor of Cancer Studies and Surgery at the University of Manchester and Honorary Consultant, Colorectal and Peritoneal Surgeon at the Christie’s NIH Foundation Trust in the UK. Professor Renehan’s clinical and academic work breaches cancer treatment and metabolic diseases. In this session, Andrew will explore key considerations in the clinical care of people living with both obesity and cancer. Please, Andrew, the floor is yours and I will enjoy your presentation.

Speaker 5
24:34 – 41:55
Thank you very much, Luca, and thank you for setting the scene there, Jennifer. My main funders are NIHR in the UK and also Cancer Research UK and I’ve also received funding from the World Cancer Research Fund. And I was hoping, okay. So it’s, you know, it’s never a problem to reiterate what your previous speaker has said. This is a big disease. In most European countries this is the second commonest cause of cancer after smoking and in women the rates of attributable risk are probably of the order of nine to ten percent. So in some countries it’s even a greater cause of cancer than smoking. However my talk is really based about what happens after the diagnosis of cancer and what’s the effect of cancer thereafter. I’m going to cover three areas. I’m going to look at prognosis. I’m going to look at the issue around dose capping in chemotherapy. And this is an example of where obesity can impact upon treatment. And I’m going to go backwards a little bit and then look at whether obesity impacts upon cancer screening. And up to about 20 years ago, we thought that if obesity increases cancer risk, the likelihood is that it also affects adversely the progression of cancer after diagnosis, and that it would be associated with a worst outcome, specifically disease-free survivals and recurrence-free survivals. And again, the WCRF recognized these set of questions, and they’re set about in the same thoroughness that Jennifer has already alluded to, this comprehensive reviews, which not only meta-analyzes the data, but also then critiques it against set criteria and comes up with this matrix of evidence, which is based on the number of studies, the quality of the data, the heterogeneity, the biological mechanisms and the size of the effect. So these are all considered by these panels. And we come up with these categories of strong evidence, weak or limited evidence, and then strong evidence of no effect. And within this, you have slightly different categorizations of wording for incidents and for survivorship. But you will see these echoed in my next lot of slides. So the CUP or the Continuous Update Program looked at initially breast cancer. This was published in 2022, just at the back end of the pandemic. And a lot of this work is thankful to a unit within Imperial College, which really are experts in the area of metro analysis and how they analyse this and present this data, as you can see, as these continuous curves. So this is a story for breast cancer and specifically for postmenopausal breast cancer. And you can see that with increasing BMI, there is a modest but steady increase in the risk of, in this case, the outcome here was breast cancer specific mortality. So this is where the death is attributed to the actual disease. So this would suggest that in this condition that being overweight and obese is in fact worsening your overall prognosis. And the panels looked at this thoroughly and they came up with the conclusion that the evidence was strong. I was fortunate to be part of a group that looked at this in more detail for colorectal cancer and this was published in the December issue of 2023. It was actually published as four papers looking at not only obesity but also other lifestyle and physical activity. But this summarizes the specific story for obesity and colorectal cancer outcomes. And specifically in this example, this is for the risk of recurrence-free survival. So again, we’re looking at the effect on outcomes that are cancer related. And you would think that this is looking favorable, or consistent, I should say, with the previous slide, when you look at the right-hand side of the curve. But you also see on the left-hand side of the curve that there’s this potential paradox that the lower weights do worse. And we now know that in cancer like colon cancer, where many of them present with emergencies, there’s in fact a lot of weight loss. And this is called reverse causation. And in this case, together with a lot of other limitations in these studies, and these are all observational studies, there was concerns about confounding, there was concerns about selection biases. So the committee in fact concluded that the evidence was limited and the likelihood of causality was in fact there was no conclusion drawing. So the conclusion here is it differs from that for breast cancer and that limits us in terms of clinicians trying to give recommendations for this cancer. We can say there are associations but we don’t know whether we can give firm recommendations that weight loss is going to impact upon the subsequent outcome and course of the disease. And this introduces the observation of the obesity paradox, which has been observed in cancer as it was observed there. And I’ll show you subsequent examples where it applies in prostate cancer. And this is a phenomenon where, in fact, being slightly overweight, you see a potential benefit, which is a paradox. But we think in a lot of cases, this is due to the crudeness of the measure of BMI, confounding detection bias, and again, this issue of reverse causation. And there’s a further specific form of selection bias called collider bias, which I’m not going in detail here, but it’s a specific area where there’s more than one risk factor which are colliding together to give an exaggerated effect. So this is an example that I was involved with some years ago with Peter Campbell in the US in the American Society for Cancer, where we had data that looked at endometrial cancer. Sorry, we did this for colorectal and for endometrial. And what it’s showing here is that they had data of pre-diagnosis and post-diagnosis BMI. And we were able to show that there is a BMI stage migration, a downward stage migration, that these people lose weight, even in those that start at obese and overweight, there is a downward migration. And this gives, again, a spurious association when it comes to looking at this in association studies. And not surprisingly, this migration was greater the greater the stage of disease. So with distant disease, you had this reverse causation, which gives a spurious outcome. I’m now going to look at the issue of dose capping. And this introduces the concept of mediation analysis. And this is asking the question, is the effect on survival, if there is an adverse effect, is it truly through a direct effect, i.e. obesity is impacting on all those hallmarks of cancer that Jennifer referred to, or in the case of cancer, is obesity or patients with obesity being adversely disadvantaged. And one way to look at this is to look at dose capping. Now at a simple level, and this is known as the indirect effect, at a simple level, we can look at the first dose of chemotherapy. So chemotherapy is given over many, many cycles. And you can look to see if the oncologist has dosed it downwards. One of our PhD students, Corinna, looked at this in great detail in a consortium across a number of out of chemotherapy trials in colon cancer. And she clearly showed across many different regimens that there is dose capping going on in the order, and these are percentages on the Y-axis, that in patients who are obese, there can be dose capping, i.e. a reduction of greater than 5% of the order of 20 or 30%. As I say, it’s across the board and you can see a stepwise effect that is significant. I won’t spend a lot of time on this, but you can go into this in a lot more detail and finesse this and look at the relative dose intensity and the cumulative relative dose. So this takes account of the fact that chemotherapy is given over many doses and the dose capping may not occur at the first dose, but it may occur subsequently. And you can look to see if this is related to obesity. And the answer is that it was. I won’t show those in detail, but this affects, disadvantages the patient with obesity across the whole course of their treatment. Another student went on to look at this as a master’s, again in the adjuvant chemotherapy setting, this time in non-metastatic, no positive breast cancer. And he looked at three large studies. You can see the sizes of them there, 700, 1600 and 900. So well over 3,000 women here, again across a variety of different regimens. And again, he consistently showed that these patients get dose capped. But he failed to demonstrate whether this actually transformed into a deleterious effect on survival, but this in turn may affect the actual numbers we were dealing with or it may affect that there are other factors involved. But there is a potential here for patients to be disadvantaged by a reduction in dose. Another student looked across five trials, this time in the metastatic setting of prostate cancer And on this occasion, we again show the dose capping, but we also showed this paradoxical inverse association with serum PSA, which is routinely measured in the metastatic setting of prostate cancer. PSA is used for screening, but it’s also used for monitoring. And these effects are absolutely enormous. These are not subtle effects that we see sometimes in the screening setting. These are huge effects. And again, we felt that in this setting, what we were demonstrating here was that with more aggressive disease, we were seeing a greater inverse association with BMI. And again, we were concerned that there was reverse causation going on in this cancer. And again, we showed the obesity paradox in this setting. So my final three slides deal with two cancer settings. This is now in screening. In the UK and in many European countries, we have routines of vital screening where women are invited free of charge in our society here in the UK to screening. But the uptake is very variable and it runs at about 65 to 70 percent. It varies by social class and also by age. But this metro analysis shows that it’s also affected by BMI. It’s a modest six or seven percent, but it’s certainly there for overweight and it increases to approximately 20% for the obese. So this is for non-participation. And almost identical results when you come to look at breast cancer. This is a Danish study, the Danish health and diet study, which again showed non-participation and you can see that there is a stepwise effect with increased obesity, there’s an increased amount of non-participation and again in this example the curve is u-shaped and those that were underweight also are an increased probability of non-participation, particularly for most for postmenopausal women. Finally, I’d like to touch on, you know, do we have enough evidence to convert these kind of questions into introducing new screening? And this is work from a Harvard group who are advocates of this issue, particularly when it comes to type 2 diabetes, which of course is an obesity-related disease. And the modelling here is showing that with type 2 diabetes, individuals with this condition have an increased risk of colorectal cancer. And they argue that this has shifted forward quite considerably. So for example, in a non type 2 diabetes population, the risk is shown here of a 45-year-old group have a 10-year cumulative risk of 0.35. And they argue in their modelling that this is shifted forward to age 36 for individuals who have diabetes. And they argue that we should be bringing forward our screening of this population, because in the US, colorectal cancer screening starts at the age of 45, we should be bringing it forward to the age of 36 in type 2 diabetes. There’s a lot of assumptions in this model and I’m not yet 100% convinced and it could have enormous impact on resources of endoscopic suites within busy hospitals, but it is something to think about. So on that note, I’d like to finish by thanking all my team, some of whom were on the webinar this morning. This photograph includes a colleague of Jennifer’s, Britt, who was part of her team before the pandemic, and she came to Manchester to share some of her methodologies in the life course epidemiology, which is most important to study this topic. So thank you very much for your time and finally to thank funders, collaborators and of course patients who contribute to this work. I’ll stop sharing and happy to take questions.

Speaker 1
41:57 – 42:20
Thank you, Andrew, and I think that we are ready for some questions. There is a lot of content in these two presentations. Please, if you have a question, write the question in the chat, because we have a lot of attendees. This is very difficult for us to manage the

Speaker 2
42:20 – 42:20
question

Speaker 1
42:23 – 43:44
individually. So please, please write your question, and I will try to ask the question to the speakers. Just for breaking the ice, I have a small question for Jennifer. – When you, Jennifer, when you show the first studies, so the studies looking at the link in between BMI in childhood and the risk for cancer in adulthood, you confirm that most of the association that we have in the past for the adults, but with one exception, and the exception was melanoma. – Yes. – And I was a bit surprised because we have a lot of data show demonstrating a clear relationship between obesity in adults and melanoma. And we have also some evidence from the Swedish Obese Subject Study that reducing weight can reduce the risk for melanoma in adulthood. So how you can explain this discrepancy? This is the only one. Maybe it’s just a matter of number, I believe. But what do you think about?

Speaker 3
43:45 – 44:27
Yeah, thank you, Luca, for that very challenging question, shall we say. I think that within every study we’re looking at, there is a confidence interval. And there’s a range of estimates that things can be. So we did not find statistical significance. Yet I do believe the hazard ratio is a little bit in the positive direction. And I think if we do look at some of these studies, as Andrew was alluding to, many of the observational studies in this area, even if it was a clinical trial, the observational follow-up in some of them when it’s a secondary outcome, there’s certain types of biases we have to consider. So people in contact, for example, with a medical system may be more likely to be in contact and more likely to have the

Speaker 2
44:27 – 44:28
melanoma found.

Speaker 3
44:29 – 44:48
But I think you’re really getting at the idea that It’s different populations, different ages, different stages. So there’s no one answer. Maybe WCF will do a meta-analysis on it and provide us with a definitive judgment on what they find. But it’s just one of those anomalies.

Speaker 1
44:51 – 44:54
– Thank you. Thank you for the answer. Of course,

Speaker 2
44:55 – 44:58
in the

Speaker 1
44:58 – 45:02
remaining part of your talk, you emphasize the space that we have for prevention.

Speaker 3
45:07 – 45:08
– Indeed, I mean, I– – But also

Speaker 1
45:08 – 45:30
you emphasize the importance to start the prevention earlier as possible. If I am correct, can you confirm or this is my opinion personally? So do we have data about effectiveness of prevention Is that it?

Speaker 3
45:32 – 46:31
– If you’re speaking of prevention of obesity in children and adolescents, unfortunately the data don’t support the current efforts. But again, I think it’s a matter of obesity is a disease and many of the preventive efforts have not targeted as such. I think that when we’re talking about prevention, a lot of the interventions we’ve seen have actually been health promotion. So it’d be quite surprising to find a strong impact in overweight and obesity in children. So I think now with the greater understanding that we have of obesity as a disease, my hope is that some of the prevention efforts will actually move into primary prevention and less away from health promotion. Health promotion is good for all, would never say anything bad about it. Let’s keep doing every effort we can there. But I think until now, perhaps they haven’t been targeted strongly enough at the right group of individuals and they haven’t been the type of sustained, intensive effort it takes to fight the biology of obesity. Andrew, if I

Speaker 1
46:31 – 46:32
pass to you, I see your

Speaker 3
46:32 – 46:33
hand is raised. Yeah.

Speaker 1
46:34 – 46:36
Thank you. I was going to go back

Speaker 5
46:36 – 47:36
to the discussion you were having about the melanoma, the links between obesity and melanoma. And I concur with Jennifer that it’s one of the cancers where there’s a lot of heterogeneity across the studies. And there’s a lot of discussion about the impact on individuals with obesity, and how it impacts upon their activities and whether they’re out there on the beaches, getting the sunshine and are, you know, playing the sports and stuff. I think that varies from population to population. And of course, it’s extraordinarily challenging to try and capture that in an epidemiological study. So it is one of those cancers where I think you will see, we will see different relationships across populations.

Speaker 3
47:38 – 47:44
Yeah, I completely agree with you, Andrew, I think it is a challenging anomaly. So well, well picked out Lucas, you found it, Luca, you found it.

Speaker 1
47:46 – 48:48
– And we have some questions from the chat now. People are stimulated to enter into the discussion, of course. And of course, the first question, a very expected one, I was preparing this question for you, Andrew. Should patients after cancer diagnosis recommend to lose weight? This is Mirjana Sumarac-Dumanovic. Of course, we cannot generalize, but do we have evidence that for at least for some type of cancer, then that proving that obesity management, effective obesity management could reduce the risk or the risk of recurrence or the risk of new cancer or improve the prognosis. We had a lot of discussion about this point, of course, you know, but what you can say today to this audience?

Speaker 5
48:49 – 51:02
– Yeah, this is an enormous challenge to make clinical recommendations. So I think the first starting point is what Jennifer has already alluded to, recommending people to attain close to a normal weight and a healthy lifestyle and healthy diet, of course, is to be recommended for anybody. That’s number one. Number two is while we have observational data, for example in breast cancer, that it may be associated with worse disease-related outcomes, we don’t have trial data that weight loss makes a difference. We have studies that are not far off being reported, like the Be Well study, which are in people who are at risk of breast cancer, but we still don’t know the full outcomes here. And the other area which I didn’t cover and is again relatively new is the pre-habilitation era. So most of us have talked about the post-cancer treatment, but there are certain cancers that lend themselves to having treatment of their overweight and obesity before the cancer treatment. We have some examples within our institute of men with prostate cancer where you can weight often up to 10-12 weeks before you actually treat the cancer. I’m talking about surgical prostatectomies, robotic surgical prostatectomies, where it’s an advantage to try and get those individuals to lose weight either by behavior or even in the example of potentially using pharmaceutical agents to get that weight off them within 12 weeks and make the surgery more efficient and hopefully reduce complication rates. At the moment this is all sounds good, but there are no large scale studies.

Speaker 1
51:05 – 51:30
Of course, the design of a study looking at the effect on this specific outcome is a problematic one. And I have a question, there is an additional question from the chat, and this is maybe much more for Jennifer. You demonstrate a connection

Speaker 2
51:30 – 51:33
between

Speaker 1
51:33 – 51:35
childhood obesity

Speaker 3
51:35 – 51:36
and cancer.

Speaker 1
51:36 – 51:58
So the question is about time of being in the obesity overweight group and the chance of cancer. I think that you partly respond to this question showing your results considering the pattern of weight instead of a single measurement, but maybe you can comment a bit more about that.

Speaker 3
51:59 – 53:30
Yeah, I mean I think having an understanding of the duration of exposure to obesity is critical. We were able to show it across childhood, but we’ve not been able to It’s not the lack of ideas. It’s not like Andrew says, it’s not the lack of understanding. It’s just in order to demonstrate this, we would really require repeated measurements at multiple ages. And even though Denmark is fantastic for registries, that’s not information we have available for everybody. I can say that we did have this information available for the children I showed you and some conscripts. So in the 60,000 men that would be, and Andrew, you’re a part of this study as well. And we were able to show that actually the duration does matter. So the longer the exposure, the higher the risk. We were really interested in seeing if change in the overweight obesity category between childhood and adulthood would reduce the risk. And maybe there were some indications but we couldn’t make any firm conclusions. I think if we sort of contrast this with adult obesity, oftentimes we take it at a single point and we ask how long have you been living with obesity? One year, five years. But again, this isn’t as good for the research purposes. It’s important information, but it’s not as analyzable as we would like it to be. But there’s no doubt that the duration of exposure matters. We just can’t fully quantify it with what we have available. I mean, Andrew, in your clinical practice, do you ask how long a person’s been living with obesity or is it just the snapshot of the individual at the moment?

Speaker 5
53:32 – 54:11
– At the moment, it’s a snapshot. that the hospital systems are still relatively crude in how we collect data. And we tend to take it as a snapshot of that window when they present. There’s all good points. We have tried to get data to get pre-diagnosis BMI ’cause that’s far more indicative. Even in those breast cancer studies, I still have nervousness that we would have been better at having studies where we had pre-BMI, ’cause that reflects the accumulation over decades.

Speaker 1
54:14 – 54:26
– Of course, there is also a question about the importance to move from BMI to body composition analysis in analyzing the link between obesity

Speaker 2
54:26 – 54:27
and cancer

Speaker 1
54:27 – 54:37
in general. Maybe this question could be good for both of you guys. So do

Speaker 2
54:37 – 54:38
you have some data?

Speaker 1
54:39 – 54:48
Do we have some data specifically looking at this relationship considering body composition analysis or not?

Speaker 3
54:49 – 54:51
– Maybe Andrew, may I go first and

Speaker 1
54:51 – 54:51
I’ll pass

Speaker 3
54:51 – 54:51
to

Speaker 5
54:51 – 54:54
you? – Yeah, absolutely. I think this is a hot area.

Speaker 3
54:54 – 55:51
– It’s absolutely hot. So I’m an epidemiologist. I’m working at the population level. at the population level, BMI is a good enough indicator of adiposity. This is why we can make these risk assessments, but we cannot do it at the individual level, because of course we do want the deeper information on body composition. We really want to know about adipose tissue and lean mass as well. The one thing to remember in the field of cancer is cancer is a disease of later life typically. So it does mean if we wish to look at childhood, we have to go back in time. And back in the 1930s, ’40s and ’50s, DEXA wasn’t being used. It’s still not actually in schools, that’s a fine thing, but this information just wasn’t available. So at the population level, we can gain insights, but I think going forward with some of the really neat cohorts now, which are really deeply phenotyped and genotyped and also have body composition, we’ll gain answers to this really important question. Andrew.

Speaker 5
55:52 – 57:38
– So we’ve been fortunate to get funding in this area. We have both PhD students and master’s students looking at this using the UK Biobank, which is, has, their intention is to get 100,000. The Biobank has 500,000 individuals and 100,000 of them have been invited back for whole body MR scanning. And we can get data on visceral adiposity, VAT, subcutaneous sat, and also liver fat, approximately up to about 47,000 at the moment. And we’re looking at the relationships with cancer outcome. Regrettably, a bit like what Jennifer says, the UK Biobank started some 15, 20 years ago. And the cohort started in with a mean age in the 50s. This group that have had imaging was later on, and the mean age is now 65. So you’re seeing the relatively late on, it’d be nicer if we got these in the 20s, 30s, 40s. and seeing these relationships. So we are seeing some signals, it’s very early, literally came to my email last Friday. So I can’t disclose it just yet, because we need to double check it. And we also have a master’s student looking at the DEXA scans within UK Biobank. So we’ll have it at the European meeting over the coming years, Luca, for your presidency.

Speaker 2
57:38 – 57:39
It will be

Speaker 1
57:39 – 57:41
a pleasure, it will be a pleasure for us.

Speaker 5
57:41 – 57:44
If you assure us, we’ll get an oral.

Speaker 1
57:46 – 57:56
Fantastic, fantastic. Maybe Istanbul or later. We will see. We will wait for you, Andrew. So

Speaker 2
57:56 – 57:57
maybe

Speaker 1
57:57 – 58:06
we have a space for the last question because we are very close to the end of the time. Of course, we have

Speaker 2
58:06 – 58:08
an answer

Speaker 1
58:08 – 59:03
about the use of the GLP-1 or in general, increasings-based therapy in people with cancer. Maria is asking about the safety of this use apart from the well-known contraindication in people with medullary thyroid cancer. Andrew, do you have experience? You talk about the use in in prehabilitation, but what about the use, for instance, in women after breast cancer surgery or chemotherapy? Because we have also the problem that these women are using hormonal therapy. They are much more prone to weight gain for several reasons. So what about your opinion about that?

Speaker 5
59:06 – 01:00:11
I should first, again, we have another PhD student looking at this question, and he’s on the call, Matt Harris. We’re looking at it mainly in the context of incidents of disease. I hadn’t started framing the question about post-diagnosis use, Lucas, so it’s relevant. very difficult in the post treatment setting because there’s just so many other treatments going on. But just because we’re running out of time, the best data we have, of course, is if you look deep within the select trial, with four and nearly four and a half years follow up, there are data on cancer outcomes, there’s no difference in the arms just yet. But we would expect it to take up to 10 years before we would see a protective effect from these drugs if there were to be one. So this is a work in progress, Luca. Definitely another hot topic.

Speaker 1
01:00:12 – 01:00:36
Okay, thank you. Thank you. Thank you to Jennifer. Thank you to Andrew for the excellent presentation. Thank you for the attendees for listening to this webinar. I am sure that we have a lot of interesting information. Please, I remember to you to complete the feedback form because it is important for us.

Speaker 4
01:00:37 – 01:00:53
And stay tuned with EASO because we will have much more webinars coming in the next months and much more events for you. Have a good night and see you soon.