Behind the Genes

A daily low dose of aspirin could significantly reduce the risk of bowel cancer in people with Lynch syndrome, an inherited condition that increases the likelihood of developing certain cancers. In this episode, we explore the findings from the landmark CaPP3 trial, hear from a participant living with Lynch syndrome, and discuss how genomics could help shift healthcare from treatment to prevention. Our host, Sharon Jones is joined by: Dr Katie Snape, Principal Clinician for Population Health at Genomics England Professor Sir John Burn, Professor of Clinical Genetics at Newcastle University Drew Hyde, participant in the Cancer Prevention Programme (CaPP3) Links: Listen to: How can genomics help us understand cancer? "I think knowing is always a good thing. And obviously, I wish I'd known earlier, and then, I could have taken more measures earlier on. So I think knowledge is definitely a good thing. And it would be great if more people could be tested or could find out if they were carriers at an early age, I think." You can download the transcript or read it below. [00:00:00] Sharon: Welcome to Behind the Genes. In today's episode, we'll explore the research which shows how a low dose of aspirin can halve the risk of bowel cancer in people with Lynch syndrome. We'll hear about the real-life impact of living with the condition, and look at how genomics can help shape a more preventative approach to care in the future. [00:00:20] I'm Sharon Jones, and to help us unpack all of that, I'm joined by our guests, Dr. Katie Snape, principal clinician for population health at Genomics England; Sir John Burn, professor of clinical genetics at Newcastle University; and Drew Hyde, a participant in the Cancer Prevention Programme, which is also known as the CaPP3 trial. [00:00:42] So to start with the basics, Katie, can you walk us through what cancer is in simple terms? [00:00:50] Katie: Sure, Sharon. So, our body is made up of cells. Those are the building blocks that, that make us as humans and other creatures and plants. And our cells need to keep dividing throughout our lifetime as our bodies are growing and working normally. [00:01:06] And so we need to have processes in place in our body where our cells can divide, but then also stop dividing when we don't need them to carry on dividing. What happens in a cancer cell is basically that cell becomes abnormal, and it doesn't follow the normal checks and balances and rules of cell division. [00:01:23] So it starts to divide and grow uncontrollably, and it can start to invade other tissues and obviously, that can cause serious consequences. [00:01:33] Sharon: We'll hear a lot more from Dr. Katie Snape in this episode. But before we move on, I just wanted to flag that there was an episode of our Genomics 101 explainer series with Katie dedicated to helping us get to grips with how genomics can help us understand and diagnose cancer. [00:01:47] Do go and check that out. We'll put a link to that in the episode description. [00:01:54] So the World Health Organization estimates between 30 to 50% of all cancers are preventable. So, Katie, when we talk about cancer being preventable, what does that actually mean? And what's an example of cancer prevention that people might already know? [00:02:11] Katie: Yeah. So some cancers are due to chance or just mistakes happening as our cells copy. [00:02:19] Other cancers are because there has been damage to the genetic information within the cell that can be caused by certain things that can cause damage to DNA. So for example, a sort of obvious answer would be skin cancer. Skin cancers can be caused by sunlight, the, the UV light in the sun, and particularly if we burn our skin or, or get sun damage to our skin, increases the chance of us developing a skin cancer. [00:02:44] So you can think of lots of other examples such as cigarette smoking and lung cancer, and so we know that there are a number of different risk factor

In this explainer episode, we’ve asked Dr Nour Elkhateeb, clinical fellow at Genomics England and clinical geneticist for the NHS, to explain the role of a clinical geneticist. The previous episode mentioned in the conversation is linked below. What is the diagnostic odyssey? You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, let us know on podcast@genomicsengland.co.uk. You can download the transcript or read it below. Florence: What is a clinical geneticist? My name is Florence Cornish and I'm here with Nour Elkhateeb, clinical geneticist for the NHS and fellow at Genomics England, to find out more. So, Nour, before we dive into talking about clinical geneticists, could you explain what we mean by the term genetics? Nour: Hi Florence, so at its heart, genetics is the study of our genes and how they are passed down through families. Think of your genome as a huge, incredibly detailed instruction manual for building and running your body. This manual is written in a specific language, DNA, which is made up of millions of letters arranged in a specific order. And here is the interesting part, we all have tiny differences in our genetic spelling, which is what makes each of us unique. But sometimes a change in the instructions, a spelling mistake in a critical place, can affect health. Genetics is all about learning to read that manual, understand how changes in it can cause disease, how it's passed down through families and finding ways to help. Florence: And so, what kind of thing does a geneticist actually do? Nour: Well, the term geneticist can cover a few different roles, which often work together. Crudely speaking, you can think of two main types, laboratory geneticists and clinical geneticists. Laboratory geneticists are the incredible scientists who work behind the scenes. When we send a blood sample for genomic sequencing, they are the ones who use amazing technology to read the billions of letters in that person's instruction manual. The job is to find the one tiny spelling mistake among those billions of letters that might be causing a health problem. Clinical geneticists like me are medical doctors specialised in the field of genetics, and we work face-to-face with patients and families in a hospital or a clinic setting. You can think of us as the bridge between the incredibly complex science of the genomics lab and the real-life health journey of the person in front of them. We diagnose, manage and provide support for individuals and families who are affected by or at risk of genetic conditions. And we translate that complex genetic information into meaningful information for the patient, the family and the other doctors as well. Florence: So, let's talk a little bit more about clinical geneticists. What stage of someone's genomics journey are they likely to see you? What are some typical reasons they might get referred, for example? Nour: That's a really good question. So, people actually can be seen by clinical geneticists at almost any stage of life, and for many different reasons. Let me give you some examples. We see a lot of babies and children. A family may be referred to us if their baby is born with health problems that do not have a clear cause, or if a child is not developing as expected. And sometimes families may have been searching for answers for years, or what we call a diagnostic odyssey, but no one has been able to find a single unifying diagnosis to explain their challenges. And our job is to see if there is a genetic explanation that can connect all the dots. Florence: You touched there on the diagnostic odyssey, and I know we don't have time to dive into that right now, but if listeners want to learn more about this, then they can check out our previous Genomics 101 podcast: What is the Diagnostic Odyssey?

In this episode of Behind the Genes, we explore the hopes, concerns and complex questions raised by the idea of a lifetime genome — a single genomic record used across a person’s life to guide healthcare decisions. Drawing on conversations from Genomics England’s Public Standing Group on the lifetime genome, our guests explore what it might mean for individuals, families and society to have their genome stored from birth, and how it could transform healthcare. The discussion reflects on the potential for earlier diagnoses, better treatments and long-term prevention, alongside pressing ethical concerns such as data security, consent, and the impact on family dynamics. Participants share their views and discuss the future role of genomic data in medicine, with insights into how trust, equity and public dialogue must shape this evolving field. Our host for this episode, Dr Harriet Etheredge, is joined by Suzalee Blair-Gordon and Gordon Bedford, two members of the Genomics England’s Public Standing Group on the lifetime genome, and Suzannah Kinsella, Senior Associate at Hopkins Van Mil, a social sciences research agency that helped to facilitate this work. Together, they consider the broader societal implications of lifetime genomic data, and how public involvement can help guide policy and practice in the UK and beyond. This conversation is part of our ongoing work through the Generation Study, exploring how genomics can be used responsibly and meaningfully from birth onwards. You can listen to some of our Generation Study episodes by following the links below. What can we learn from the Generation Study? How has design research shaped the Generation Study? What do parents want to know about the Generation Study? "This isn’t just a science project, it’s about designing a future where everyone feels included and protected. We need more voices, parents, young people, underrepresented communities, to keep shaping it in the right direction." You can download the transcript, or read it below. Harriet: Welcome to Behind the Genes. Suzalee: I have come to terms with the thought that life is unpredictable and I have already begun to accept any health condition that comes my way. Believe you me, I have been through the stage of denial, and yes, I have frozen upon hearing health diagnoses in the past but now I believe that I am a bit wiser to accept the things that I cannot change and to prepare to face the symptoms of whatever illness I am to be dealt with or to be dealt to me. If the analysis of my genome can help me to prepare, then yes, I am going to welcome this programme with open arms. Harriet: My name is Harriet Etheredge, and I am the Ethics Lead on the Newborn Genomes Programme here at Genomic England. On today’s episode I’m joined by 3 really special guests, Suzalee Blair and Gordon Bedford, who are members of Genomics England’s Public Standing Group on Lifetime Genomes, and Suzannah Kinsella, Senior Associate at Hopkins Van Mil, a social sciences research agency that has helped us to facilitate this work. Today we’ll be discussing the concept of the lifetime genome. What do we mean when we say, ‘lifetime genome’? How can we realise the promise of the lifetime genome to benefit people’s healthcare whilst at the same time really appreciating and understanding the very real risks associated? How do we collectively navigate ethical issues emerging at this genomic frontier? If you enjoy today’s episode, we would really love your support. Please share, like and give us a 5-star rating wherever you listen to your podcasts. And if there’s a guest that you’d love to hear on a future episode of Behind the Genes, please contact us on podcast@genomicsengland.co.uk. Let’s get on with the show. I’ll start off by asking our guests to please introduce yourselves. Suzalee, over to you. Suzalee: Thanks, Harriet. So I am a proud mum of two kids, teacher of computing at one of the best academic trusts in the UK, and I am also

As of February 2025, the Generation Study has recruited over 3,000 participants. In this episode of Behind the Genes, we explore what we have learnt so far from running the study and how it continues to evolve in response to emerging challenges. The conversation delves into key lessons from early recruitment, the challenges of ensuring diverse representation, and the ethical considerations surrounding the storage of genomic data. Our guests discuss how ongoing dialogue with communities is helping to refine recruitment strategies, improve equity in access, and enhance the diversity of genomic data. Our host Vivienne Parry, Head of Public Engagement at Genomics England, is joined by Alice Tuff-Lacey, Program Director for the Generation Study; Dalia Kasperaviciute, Scientific Director for Human Genomics at Genomics England; and Kerry Leeson Bevers, CEO of Alström Syndrome UK. For more information on the study, visit the Generation Study website, or see below for some of our top blogs and podcasts on the topic: Podcast: What do parents want to know about the Generation Study? Podcast: How has design research shaped the Generation Study? Blog: What is the Generation Study? "We always have to remember, don’t we, that if people say no to these things, it’s not a failure to on our part, or a failure on their part. It’s just something they’ve thought about and they don’t want to do, and for all sorts of different reasons. And the other reflection I have about different communities is the ‘different’ bit, is that what approach works for one community may not work for another, and I think that that’s something that’s going to have to evolve over length of the study, is finding the things that are the right way, the most helpful way to approach people." You can download the transcript, or read it below. Vivienne: Hello and welcome to Behind the Genes. Alice: “And this is quite an exciting shift in how we use whole genome sequencing, because what we are talking about is using it in a much more preventative way. Traditionally, where we’ve been using it is diagnostically where we know someone is sick and they’ve got symptoms of a rare condition, and we’re looking to see what they might have. What we’re actually talking about is screening babies from birth using their genome, to see if they are at risk of a particular condition, and what this means is this raising quite a lot of complex ethical, operational, and scientific and clinical questions.” Vivienne: My name’s Vivienne Parry, and I’m Head of Public Engagement here at Genomics England, and I’m your host on this episode of Behind the Genes. Now, if you are a fan of this podcast, and of course you’re a fan of this podcast, you may have already heard us talking about the Generation Study, the very exciting Genomics England research project which aims to screen 100,000 newborn babies for over 200 genetic conditions using whole genome sequencing. Well, we’ve got more on the study for you now. What we’re doing to make it both accessible and equitable for all parents-to-be, and our plans to ensure that we continue to listen to parents, and perhaps in future, the babies as they grow up. We’ll chat, too, about emerging challenges and how we might deal with them. I’m joined in our studio by Alice Tuff-Lacey, the Programme Director for the Generation Study, and Dalia Kasperaviciute, Scientific Director for Human Genomics, both from Genomics England, and we’re delighted to welcome Kerry Leeson-Bevers, Chief Executive of Alström Syndrome UK. And I’m just going to quickly ask Kerry, just tell us about Alström Syndrome and how you’re involved. Kerry: Yes, so Alström Syndrome is an ultra-rare genetic condition. My son has the condition and that’s how I got involved. So, the charity has been around now since 1998, so quite a well-established charity, but as part of our work we developed Breaking Down Barriers, which is a network of organisations working to improving enga

In this episode, our guests explore the impact of genetic discoveries on inherited retinal dystrophies, in particular retinitis pigmentosa (RP). The discussion highlights a recent study that identified two non-coding genetic variants linked to RP, predominantly in individuals of South Asian and African ancestry. The conversation highlights how advances in whole genome sequencing are uncovering previously hidden causes of genetic disease, improving diagnostic rates, and shaping the future of patient care. It also addresses the challenges faced by individuals from diverse backgrounds in accessing genetic testing, including cultural barriers, awareness gaps, and historical underrepresentation in genomic research. Our host Naimah Callachand is joined by researcher Dr Gavin Arno, Associate Director for Research at Greenwood Genetic Centre in South Carolina, Kate Arkell, Research Development Manager at Retina UK, and Bhavini Makwana, a patient representative diagnosed with retinitis pigmentosa and Founder and Chair of BAME Vision. We also hear from Martin Hills, an individual diagnosed with autosomal dominant retinitis pigmentosa. To access resources mentioned in this episode: Access the Unlock Genetics resource on the Retina UK website Visit the BAME vision website for more information and support Find out more about the groundbreaking discovery of the RNU4-2 genetic variant in the non-coding region which has been linked to neurodevelopmental conditions in our podcast episode "Discoveries like this lead to better clinical management. We understand better the progression of the disease when we can study this in many individuals from a wide spectrum of ages and different backgrounds. We can provide counselling as Bhavini was talking about. We can provide patients with a better idea of what the future may hold for their eye disease, and potentially, you know, we are all aiming towards being able to develop therapies for particular genes and particular diseases." You can download the transcript or read it below. Naimah: Welcome to Behind the Genes. Bhavini: The few common themes that always come out is that people don’t really understand what genetic testing and counselling is. They hear the word counselling, and they think it is the therapy that you receive counselling for your mental health or wellbeing. There is already a taboo around the terminology. Then it is lack of understanding and awareness or where to get that information from, and also sometimes in different cultures, if you have been diagnosed with sight loss, you know blindness is one of the worst sensory things that people can be diagnosed with. So, they try and hide it. They try and keep that individual at home because they think they are going to have an outcast in the community, in the wider family, and it would be frowned upon). Naimah: My name is Naimah Callachand and I am Head of Product Engagement and Growth at Genomics England. I am also one of the hosts of Behind the Genes. On today’s episode I am joined by Gavin Arno, Associate Director for Research at Greenwood Genetic Centre in South Carolina, Kate Arkell, Research Development Manager at Retina UK, and Bhavini Makwana, patient representative. Today we will be discussing findings from a recently published study in the American Society of Human Genetics Journal which identified two non-coding variants as a cause of retinal dystrophy in people commonly of South Asian and African ancestry. If you enjoy today’s episode, we’d love your support. Please like, share, and rate us on wherever you listen to your podcasts. Okay, so first of all I would like to ask each of the three of you to introduce yourselves. Bhavini, maybe we’ll start with you. Bhavini: Hi, I’m Bhavini Makwana, patient representative, and also Chair of BAME Vision. I have other roles where I volunteer for Retina UK, and I work for Thomas Pocklington Trust. Naimah: Thanks Bhavini. Gavin. Gavin: Hi, my name is Gavin Arno, I a

In this explainer episode, we’ve asked John Pullinger, Senior Bio Sample Operations Manager at Genomics England, to explain what it means to go on a diagnostic odyssey. You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel. If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk. The episodes mentioned in the conversation are linked below. Hope for those with no primary findings The impact of a genetic diagnosis on mental health You can download the transcript or read it below. Florence: What does it mean to go on a diagnostic odyssey? I'm joined by John Pullinger, Senior Bio Sample Operations Manager for Genomics England to find out more. So, John, first of all, can you explain what we mean by diagnostic odyssey? John: Yes, of course. The diagnostic odyssey is a term used to describe the journey that many people with rare conditions and their families undertake to receive an accurate diagnosis, a journey that takes on average over five and a half years. The rarity of the condition means that there are few, if any, other people affected by it, for doctors to draw their experience from. Some individuals might never receive a diagnosis. My job involves making sure that samples sent through the Genomics England processes can travel smoothly from the NHS hospitals to be sequenced and the results be reported back to the individual. We try and minimise the amount of time that samples and associated data is in our care. Florence: And for people listening who might not know, could you explain why it sometimes takes a long time for people to receive a diagnosis? John: There are estimated to be over 7,000 rare conditions. This means that healthcare professionals may not be familiar with all of them and so may not recognise them or know how to test for them. In addition to this, some conditions affect multiple parts of the body. For example, skin, the heart, and the lungs. In these cases, there will be a need to visit specialists from multiple departments, and each will be looking specifically at their own area. This could lead to referral loops where the patient needs to consult multiple healthcare professionals, all of which contributes to the time taken to receive a diagnosis. Since, for the majority of rare conditions, there is an underlying genetic cause. This means that most individuals who get a diagnosis will receive one through genomic testing, whether that be whole genome sequencing as offered here at Genomics England, or more targeted panel testing. Typically testing will identify a particular gene, which is known to be linked to a specific condition. For certain conditions, it requires a real expert in the condition to even think about testing for it. Sometimes a condition will present in a way that is different to most other people who have it. So they may have symptoms that others don't. This also adds to the buildup of time taken to receive the diagnosis. Florence: So, you mentioned earlier, John, that the diagnostic odyssey lasts an average of five and a half years. Can you explain what kind of effect this long waiting time has on individuals and their families? John: Absolutely. One aspect of the diagnostic odyssey that is important to recognise is the physical effect of the as yet undiagnosed condition that's present and affecting the individual and their family on a daily basis. Those with rare conditions may be affected by a range of emotions connected to the ongoing journey that they're on, including feelings of isolation. Also stress and anxiety. The fear of unknown can have a massive knock-on effect on the mental health of the individual and their family. And it's important to recognise the signs of this so that people can take steps to manage their mental health. Many rare conditions first present themselves in children and young