Childhood home temperature and community connectedness can help predict how U.S. residents set their thermostats, offering new ways to encourage energy conservation and combat climate change, according to a study published July 3 in the open-access journal PLOS Climate by Dritjon Gruda from the National University of Ireland Maynooth and Paul Hanges from the University of Maryland.
Half of U.S. households’ annual electricity use goes to heating and cooling, but less than half of homeowners tweak their thermostats to save energy throughout the day. Reducing residential energy consumption (which occupies 21% of the U.S. energy pie chart) is therefore a promising strategy for curbing national energy consumption and burning fewer fossil fuels. But first, scientists seek a reliable way to provide evidence for policy makers to incentivize at-home energy conservation.
To investigate why U.S. adults heat and cool their homes the way they do, Gruda and Hanges surveyed 2,128 participants, who reported the average winter thermostat settings in their current and childhood homes. They also rated their emotional connectedness to their current communities, a metric referred to as “community fit.” The researchers controlled for age, gender, and household income, and participants were representative of the U.S. population.
Results indicated that participants’ childhood home temperatures positively predicted their current home temperatures. For example: of people who live in cold-winter locales like New York, those raised in warmer homes tend to dial up their thermostats higher than those reared in cooler abodes.
Additionally, the researchers observed that individuals with a strong sense of community belonging were more likely to align their home temperature settings with others in their community. For example: a New Yorker with strong community ties may keep their indoor climate cooler, while someone less enamored with the Big Apple may turn up the heat.
These results suggest that “policymakers may need to pivot towards campaigns that deeply resonate with the unique identity and values of individual communities” to encourage energy conservation, the researchers state.
The authors acknowledge that community connectedness may not translate directly to energy savings, especially in affluent communities, and encourage longitudinal studies to address household income and other contributing factors.
Summarizing, the authors add: “Community fit determines how low you set your thermostat during winter, and how much heating energy you save.”

Higher inflammation in young adulthood linked to lower performance in skills testing in midlife.
Young adults who have higher levels of inflammation, which is associated with obesity, physical inactivity, chronic illness, stress and smoking, may experience reduced cognitive function in midlife, a new study out of UC San Francisco has found.
Researchers previously linked higher inflammation in older adults to dementia, but this is one of the first studies to connect inflammation in early adulthood with lower cognitive abilities in midlife.
“We know from long-term studies that brain changes leading to Alzheimer’s disease and other dementias may take decades to develop,” said first author Amber Bahorik, PhD, of the UCSF Department of Psychiatry and Behavioral Sciences and the Weill Institute for Neurosciences. “We wanted to see if health and lifestyle habits in early adulthood may play a part in cognitive skills in midlife, which in turn may influence the likelihood of dementia in later life.”
In their study, publishing in Neurology on July 3, researchers found that only 10% of those with low inflammation performed poorly on testing of processing speed and memory, compared to 21% and 19%, respectively, of those with either moderate or higher levels of inflammation.
When researchers adjusted for factors like age, physical activity and total cholesterol, disparities remained in processing speed; and the researchers also found differences in executive functioning, which includes working memory, problem solving and impulse control.
The study followed 2,364 adults in the CARDIA study, which aims to identify the factors in young adulthood that lead to cardiovascular disease two-to-three decades later.

Participants were 18 to 30 years old when they entered the study and were tested four times over an 18-year period for the inflammatory marker C-reactive protein (CRP). They took the cognitive tests five years after their last CRP measurement, by which time most participants were in their forties and fifties.
About half the participants were female; a little under half were Black, and the rest were white. Some 45% had lower stable inflammation, while 16% had moderate or increasing inflammation; 39% had higher levels.
A link between inflammation and health risks
The researchers also linked higher levels of inflammation with physical inactivity, higher BMI and current smoking.
“Inflammation plays a significant role in cognitive aging and may begin in early adulthood,” said senior author Kristine Yaffe, MD, a professor of psychiatry and behavioral sciences, neurology, and epidemiology and biostatistics at UCSF. “There is likely a direct and indirect effect of inflammation on cognition.”
Yaffe is a member of the first team of experts to determine that 30% of dementia risk is preventable. Her recent research has looked at the association in midlife between fragmented sleep and lower cognition and the effects of personalized health and lifestyle changes in preventing memory loss in higher-risk older adults.
“Fortunately, there are ways to reduce inflammation — such as by increasing physical activity and quitting smoking — that might be promising paths for prevention,” Yaffe said.

Swedish researchers have created a questionnaire test for home use that quickly identifies high risk of heart attack. A study shows that it has the same level of accuracy as blood tests and blood pressure measurements.
The study, published in Journal of the American Heart Association, uses data from the SCAPIS population study, which is based at the University of Gothenburg, with the Swedish Heart Lung Foundation as its main sponsor.
The study was led by Göran Bergström, Professor of Clinical Physiology at Sahlgrenska Academy at the University of Gothenburg, senior physician at Sahlgrenska University Hospital, and principal investigator for SCAPIS.
“A heart attack often comes out of the blue,” he says. “Many of those who suffer heart attacks are apparently healthy and asymptomatic, but have fatty deposits in the coronary arteries, known as atherosclerosis. Our test makes it possible to identify almost two-thirds of people aged 50-64 who have significant coronary atherosclerosis and are therefore at high risk of cardiovascular disease.”
Algorithm identifies people at risk
The home test consists of 14 questions that take five to eight minutes to answer. These questions relate to factors including age, gender, weight, waist circumference, smoking, high blood pressure, high blood fats, diabetes, and family history of cardiovascular disease.
According to the study, by combining information from the responses in a special algorithm, the home test can detect 65% of individuals at the highest risk of cardiovascular disease.

“The results show that our home test is as accurate as a clinic examination using blood tests and blood pressure measurements,” continues Professor Bergström. “If we can make the test widely available within healthcare, it can save lives and prevent suffering by helping us to identify those who are at high risk of heart attack or who are currently undertreated.”
Early warnings can save lives
The study is based on data from 25,000 individuals aged 50-64 included in SCAPIS. All participants had their coronary arteries examined using computed tomography, which provides an image of the degree of atherosclerosis.
By comparing the images of the heart with questionnaires completed by the participants, the researchers were able to see which factors had the closest links with the degree of atherosclerosis. The research team has also launched studies in Sweden and on data from the United States, to evaluate how the test works on different groups.
Identifying people at risk before disease occurs is one of the main objectives of the Swedish Heart Lung Foundation’s focus on SCAPIS. As the foundation’s Secretary-General Kristina Sparreljung explains:
“A test that can provide early warnings would save many lives and a great deal of suffering. The results of Professor Bergström’s study are therefore extremely interesting.”

Neuroendocrine tumors, including small cell lung cancer and neuroendocrine prostate cancer, are very aggressive with high chances of spreading. However, many individuals develop resistance to few available treatment options, leading to poor patient outcomes. Researchers are therefore aiming to develop new therapeutic methods that focus on the disease-specific molecular mechanisms of these tumors.
In a recent article published in Molecular Therapy: Nucleic Acids, a team of researchers at Osaka University describe a strategy targeting one such mechanism, called RNA splicing.
RNA splicing is the process by which cells remove certain portions of messenger RNA (mRNA) molecules. This produces the mature mRNA that contains the instructions for making a protein for a specific gene. Because incorrect RNA splicing can result in dysfunctional or overactive proteins, this process can significantly contribute to disease development.
The team focused on a protein named the RE1-silencing transcription factor (REST), which typically represses certain genes that support neuroendocrine phenotypes. Interestingly, an abnormally spliced form of REST mRNA is expressed at high levels in neuroendocrine tumors.
“Incorrect splicing of REST mRNA can cause the resulting protein to lose its function, which can lead to neuroendocrine cancer development,” says Keishiro Mishima, lead author of the study. “Our group aimed to develop a molecular method that could be used to correct REST splicing patterns.”
The team used molecules called amido-bridged nucleic acid-based splice-switching oligonucleotides (SSOs). These SSOs were designed to interact with a specific portion of the REST mRNA molecule, allowing it to splice into its normal form. The researchers implanted neuroendocrine cancer cells under the skin of lab mice to form tumors. They then injected the mice into the abdomen with saline or SSO, monitored tumor growth and collected blood samples.
“We examined the levels of certain biochemical markers in the mice serum samples to ensure the SSO treatment did not induce any liver toxicity,” explains Masahito Shimojo, senior author “In parallel, we treated neuroendocrine cancer cell lines in culture with the SSOs to obtain in vitro data to support our in vivo findings.”
REST SSO treatment led to considerably fewer viable cancer cells than the control treatment. In addition, a significantly reduced tumor size was observed in mice injected with REST SSOs. The team then conducted further molecular analyses to examine the expression patterns of the genes that REST typically represses under normal conditions.
“Following treatment, REST-controlled gene expression levels significantly decreased in SSO-treated tumors compared with the control-treated tumors,” says Shimojo. “This indicated that the SSO promoted the restoration of REST function.”
Overall, the study demonstrates that this unique and novel therapeutic approach holds promise for intractable neuroendocrine cancers.

A new Finnish study from University of Turku shows that already a 30-minute exercise can increase the proportion of tumor-killing white blood cells in the bloodstream of breast cancer patients.
White blood cells, the cells of our immune system, fight against cancer, bacteria, and viruses. However, not all white blood cells destroy cancer cells and some can even promote cancer growth. The most important cell types that destroy cancer cells are cytotoxic T cells and natural killer cells. Cell types that support cancer growth include, for example, regulatory T cells and myeloid derived suppressor cells.
“The balance of different types of white blood cells determines whether the immune system works to destroy cancer or to support it. If there are more cancer-destroying cells than cancer-promoting cells in the tumor area, the body is more capable of fighting cancer,” says lead author, Doctoral Researcher Tiia Koivula from the University of Turku, Finland.
Twenty breast cancer patients who had just been diagnosed and therefore had not yet started their cancer treatments participated in the study. During the study, the patients pedaled a bicycle ergometer for 30 minutes at a resistance of their own choosing. Blood samples were taken from the patients at rest before the pedaling, during the exercise, and after the exercise.
Blood samples were analysed to calculate the amount of many different types of white blood cells, and the amounts measured during the exercise were compared to those at rest.
During the exercise, the amount of several different white blood cell types increased in the bloodstream. The number of cancer-destroying cytotoxic T cells and natural killer cells increased the most. On the other hand, the number of cancer-promoting regulatory T cells and myeloid derived suppressor cells did not change.
The researchers also examined the proportions of different white blood cell types relative to the total white blood cell count, and found that the proportion of natural killer cells increased significantly, while the proportion of myeloid derived suppressor cells decreased.

“We found that during the exercise, the number and proportion of cancer-destroying cells increases in the bloodstream, while the proportion of cancer-promoting cells either stays the same or decreases. However, it is still unclear whether these changes seen in the bloodstream also lead to changes in the white blood cell counts in tumor area,” says Koivula and continues:
“In this study, it was seen that the number of almost all white blood cell types decreased back to resting values one hour after the exercise. With the current knowledge, we cannot say where the white blood cells go after the exercise, but in preclinical studies, cancer-destroying cells have been seen to migrate into the tumor area.”
The researchers also analysed whether different types of breast cancer affect the exercise responses of white blood cells. The researchers found that the larger the tumor, the less the number of natural killer cells increased, and if the breast cancer was estrogen and/or progesterone receptor-positive, the number of cytotoxic T cells increased less than in hormone receptor-negative cancers.
“In our previous study, we found small indications that the type of breast cancer might affect the effects of exercise on white blood cells, which is why we wanted to examine it further. However, the correlations we found were not very strong and therefore, no decisive conclusions can be drawn from the results. According to current knowledge, it is beneficial for all cancer patients to exercise, and our recent study supports this notion,” Koivula encourages.

If you feel like your six-year-old has suddenly gotten extra fussy about the texture of their dinner, don’t worry. It will pass. A new study from the University of Copenhagen’s Department of Food Science demonstrates that at the age of six, children prefer to avoid crunch in their peanut butter, berries in jam and pieces of fruit in yogurt,
In the study, the researchers asked 485 children between the ages of five and twelve to choose between six different foods with and without lumps, seeds and pieces of fruit in them. The foods were bread, orange juice, peanut butter, strawberry jam, yogurt and tomato soup. The researchers showed children drawings of these foods both with and without lumps, and then asked them to choose between them.
In 76 percent of the instances, six-year-olds opted for foods without lumps, the highest preference rate observed across the age groups.
“The fact that children in general are not happy with too many lumps in food is probably something many people can recognize, but this is the first time that a scientific study has linked a specific age group, namely six-year-olds, so clearly to this food preference,” says Dr. Ching Yue Chow, first author of the study.
To get answers that were as precise as possible, the researchers have used real foods to test how consistent children were in answering these questions in other studies.
Protection against dangerous foods
According to Ching Yue Chow, there may be an explanation for why children’s fear of complex texture in food peaks around the age of six.

“Food neophobia is often described as the reluctance to eat new or unfamiliar foods. It is thought to be a protective function to prevent children from eating potentially poisonous foods or other dangerous things when they start to become more independent. Studies have reported that food neophobia starts from a low baseline at weaning. It increases sharply as a child becomes more mobile and independent, reaching a peak at around 6 or 7 years old.
As such, it makes sense that this particular group in our study does not like too many lumps in food, as it is at this age that they are most cautious when it comes to food,” explains Ching Yue Chow.
The researchers also examined whether chunk size in food has anything to say. But here, they found no unequivocal answer.
“It seemed that the children generally had no problem in distinguishing different sizes of chunks when foods were in their mouths. For them, it’s mostly about the presence or absence of chunks,” says Ching Yue Chow.
However, despite there being a low point in the desire to eat food with chunks at the age of six, it gradually goes the other way in 7-12-year-olds, the study shows. And this is supported by our previous knowledge in advance of how children’s food preferences mature with age.
“As children reach school age, they may become more influenced by classmates and others within their circle to try new types of food and have more of a desire to expand their horizons. We can also see that the proportion that would like to have food with chunks in food grows in concert with their age in the study,” says Ching Yue Chow.

New dishes may need to be introduced 8-15 times
And according to the researcher, the “anti-chunk phase” that 6-year-olds have, you have to accept as a parent, although it can be frustrating when the kids don’t want to eat the food they’re served. But that can easily change once they’re past the critical age of six. You just have to keep trying — often up to 15 times, the recommendation goes:
“A lot of research on children and foods shows that repeated exposures to new dishes have a positive effect on whether they’ll bother eating them. Specifically, it is about giving children the opportunity to taste new food while there is something on the plate that they already know. Often they need to be presented with the new dish 8-15 times before they develop preference for it, but persistence pays off,” explains Ching Yue Chow.
Furthermore, it’ a good idea to avoid compulsions and rewards for children to eat their vegetables.
“Rewarding a child with an ice cream if they eat their broccoli, is a very short-term strategy. Because the moment you remove the ice cream, they don’t want to eat the healthy foods. At the same time, you shouldn’t pressure a child or try to force them to eat certain things, because you risk that they will eat the new food even less than before because they associate it with something negative,” says Ching Yue Chow.
The new research results shed more light on the food preferences of children between the ages of five and twelve, which the researcher hopes can make parents and the food industry wiser about our relationships with food.
“It is important to understand the underlying psychology of children when you, as a parent, serve them food and when you as a company develop new products to avoid children becoming unnecessarily picky. Here, I hope that our study can serve as an inspiration to parents and those who develop new food products,” concludes Ching Yue Chow.
The 6-year-olds like lumps in their food the least:
About the study: The research was carried out in a close collaboration between Future Consumer Lab, Department of Food Science, University of Copenhagen and the CASS Food Research Centre at Deakin University, Australia. The researchers behind the study are: Ching Yue Chow, Anne C. Bech, Annemarie Olsen, Russell Keast, Catherine G. Russell and Wender L.P. Bredie. The study involved 485 Australian children aged 5-12 years. The study is funded by Innovation Fund Denmark and Arla Foods.

As COVID-19 spread globally in 2020, many countries swiftly closed their borders to prevent the disease from entering. However, there was little scientific evidence to support the effectiveness of such measures.
While post-COVID research has extensively focused on the efficacy of internal travel restrictions, cross-border travel has received less attention due to challenges in accessing quality data. In a major multidisciplinary collaboration effort across Finland, Sweden, Norway, and Denmark, a group of researchers — including mathematicians, physicists and computer scientists — have published a pioneering study on the spread of infections across Nordic borders from spring until the end of 2020. The report sheds light on the efficacy of cross-border travel restrictions, helping us better understand which measures actually make a difference.
‘There have been many studies using data and modelling within countries, but this cross-border research is rather unique,’ says Associate Professor of Mathematics Lasse Leskelä from Finland’s Aalto University.
The researchers developed a sophisticated mathematical model relying on a long trail of footwork gathering travel data from the four neighbouring countries. Focus was on the short-term spread of the disease at a stage of the pandemic when infections had already started to spread within each country.
Border closures a blunt tool
The modelling revealed that cross-border closures were only likely to have significant impact in very specific scenarios. For example, a substantial disparity in disease prevalence between two countries would have to be accompanied by a high volume of cross-border traffic for restrictions to notably impact spread. It is notable that even though Sweden’s comparatively loose restrictions in 2020 contributed to the nation having vastly more case numbers than in neighbouring Finland, the overall impact of cross-border travel on the Finnish disease situation was low in absolute terms.
‘The way I see these results is that the closing of borders was mostly not very well justified. This was done out of uncertainty, because countries did not know what else to do. Since it has so many adverse effects, my take on this is that in the future, such drastic measures must be very carefully considered’, says Professor Tapio Ala-Nissilä from Aalto University.

However, the researchers point out that in different stages of a pandemic situation, there can be many layers of complexity. If a government must act, choosing between restricting local populations within its borders versus restricting travel across them, the latter may prove the better option.
‘According to our model, travellers from Sweden were over 10 times more likely to have COVID-19 in the summer of 2020 than the domestic Finnish population. So if you think about when the restrictions should hit and who should be affected, it would make more sense to place restrictions on these travellers at this time,’ Assistant Professor Mikko Kivelä from Aalto University points out.
The model also shows interesting differences between types of travel. Commuters, who may spend half a day in the destination country at a time, played a smaller role in spreading infections than vacationers who possibly spent their entire infectious periods in the country.
Preparing for the next pandemic
Kivelä emphasises that in spring 2020, decision-makers were faced with myriad uncertainties that made it impossible to reliably analyse and estimate the effects of their countermeasures. This is also where the current study makes its most significant contribution — as a predictive model for future use.
‘The really important part is that we have developed different ways of looking at this question: a mathematical machinery to answer questions about what border control interventions are necessary and when to apply,’ says university researcher Mikhail Shubin from the University of Helsinki.
Although the current study pertains to the Nordics, the researchers say that it can be applied to other countries as well. The main concern is getting reliable and comparable data. Often, even if the outward appearance of a particular data set is promising, details like reporting delays will complicate its usage.
‘Access to mobility is not easy to gain, and within the Schengen area in particular there is no detailed tracking for who moves where. You need to have access to lots of data sets, from road crossings to railroads, ferries and aeroplanes. We also used mobile phone data to validate our findings,’ explains Leskelä. ‘Usually, to do this detailed modelling, you need personal contacts and you need to build trust.’
The study is part of the NordicMathCovid project. The project includes teams from Finland, Sweden and Norway and involves a number of universities and public institutions across the Nordics. Supported by NordForsk, the project started in September 2020 and has produced research on pandemic flows and vaccination strategies from varying angles.

Chemists have overcome a major hurdle in synthesizing a more stable form of heterocycle — a family of organic compounds that are a common component of most modern pharmaceuticals.
The research, which could expand the toolkit available to drug developers in improving the safety profiles of medications and reducing side effects, was published in Science by organic chemists at the University of British Columbia (UBC), the Massachusetts Institute of Technology (MIT), and the University of Michigan.
“Azetidines are a particularly useful, stable form of heterocycle, but synthesizing them has been incredibly challenging,” says Dr. Corinna Schindler, Canada Research Chair in synthetic solutions for bioactive compounds at UBC and senior author on the paper.
Heterocycles play a major role in the design of modern drug families — including cancer drugs and antibiotics. Some reviews indicate 85 per cent of all biologically active chemical entities contain a heterocycle.
But many heterocycles currently used in pharmaceutical design tend to oxidize under physiological conditions. This can lead to off-target effects and challenges with the safety profiles of medications.
Azetidines — organic compounds that contain three carbon atoms and one nitrogen atom, and are liquid at room temperature — are known to be metabolically robust and don’t undergo oxidation reactions under physiological conditions.
“This is something that synthetic organic chemists have tried to achieve for a long time, and we’re hopeful this will enable researchers to develop new synthetic transformations of azetidines with more useful chemical and medical functions,” says Dr. Schindler, whose lab conducted the research at the University of Michigan with graduate student Emily Wearing and in conjunction with Dr. Heather Kulik’s lab at the Massachusetts Institute of Technology.
The team used light-driven reactions and a computational approach to the problem and for the first time were able to engage compounds called imines productively in reactions to form new azetidines.

The use of wearable electronics that continuously monitor biosignals has transformed the healthcare and fitness industries. These devices are becoming increasingly common and are projected to reach a market valuation of approximately USD 572.06 billion by 2033. With this rapid growth, there is an escalating demand for high-quality bioelectrodes capable of accurately recording biosignals over extended periods. However, many of the materials currently used for bioelectrodes, such as metals, conductive polymers, and hydrogels, have limitations. They often lack the flexibility to stretch the skin without breaking and have low humidity permeability, leading to sweat buildup and discomfort.
To address these limitations, in a study published in the journal NPG Asia Materialson 20 June 2024, a research team led by Assistant Professor Tatsuhiro Horii and Associate Professor Toshinori Fujie from Tokyo Institute of Technology (Tokyo Tech) has developed a bioelectrode material that is stretchable and permeable to humidity and conforms closely to the skin. This innovative material is composed of layers of conductive fibrous networks consisting of single-wall carbon nanotubes (SWCNTs) on a stretchable poly(styrene-b-butadiene-b-styrene) (SBS) nanosheet. The nanosheet conforms tightly to the skin, allowing for precise biosignal measurements, while the carbon nanotube fibers maintain the material’s stretchability and humidity permeability.
“Self-supporting electrodes that are stretchable, permeable to humidity, and conformable to skin surface bumps are required to allow for the natural deformation of skin without restricting body movements,” says Horii.
The researchers applied SWCNTs as aqueous dispersions onto SBS nanosheets, creating multiple layers reaching a thickness of only 431 nm. Each coating of SWCNTs increased the density and thickness of the fibers, modifying the bioelectrode’s characteristics. While adding more SWCNT layers increased nanosheet stiffness (from an initial 48.5 MPa elastic modulus to 60.8 MPa for a single layer and 104.2 MPa for five layers), the bioelectrode maintained impressive flexibility. Pristine SBS nanosheets and those with one or three layers of SWCNTs (SWCNT 3rd-SBS) stretched elastically by 380% of their original length before permanent deformation. This flexibility surpasses metal electrodes like gold, which have Young’s moduli in the several-hundred-GPa range and can only stretch less than 30% of their original length before breaking.
Another crucial requirement for bioelectrodes is high water vapor permeability to prevent sweat buildup during exercise. Adding SWCNTs is beneficial as its fibrous network structure improves breathability compared to continuous films. In experiments measuring water vapor transmission rate (WVTR), researchers found that SWCNT 3rd-SBS exhibited a WVTR of 28,316 g m-2 (2 h)-1, which is twice that of normal skin.
The bioelectrode material is also highly resilient for extended use. To test the material’s durability, the researchers immersed the bioelectrodes in artificial sweat and subjected them to repeated bending, measuring the change in resistance. In these tests, they found that the resistance increased negligibly, by only 1.1 times in sweat and by 1.3 times over 300 cycles of bending. Furthermore, the SWCNT 3rd-SBS nanosheets showed little to no detachment after being rubbed ten times, indicating its suitability for prolonged use.
To assess its real-world performance, the researchers compared an SBS nanosheet with three layers of SWCNT to commercially available bioelectrode materials such as Ag/AgCl gel electrodes. The bioelectrodes were attached to the forearm, and surface electromyography (sEMG) measurements were taken during gripping motions. In this experiment, the performance of the SWCNT-SBS nanosheet was comparable to that of commercial Ag/AgCl gel electrodes, achieving similar signal-to-noise ratios of 24.6 dB and 33.3 dB, respectively.
“We obtained skin-conformable bioelectrodes with high water vapor permeabilities, which showed comparable performance in sEMG measurements to those of conventional electrodes,” concludes Fujie, highlighting the material’s promising capabilities for healthcare wearables.

Bowel cancer cells have the ability to regulate their growth using a genetic on-off switch to maximise their chances of survival, a phenomenon that’s been observed for the first time by researchers at UCL and University Medical Center Utrecht.
The number of genetic mutations in a cancer cell was previously thought to be purely down to chance. But a new study, published in Nature Genetics, has provided insights into how cancers navigate an “evolutionary balancing act.”
The researchers found that mutations in DNA repair genes can be repeatedly created and repaired, acting as ‘genetic switches’ that take the brakes off a tumour’s growth or put the brakes back on, depending on what would be most beneficial for the cancer to develop.
Researchers say the findings could potentially be used in personalised cancer medicine to gauge how aggressive an individual’s cancer is so that they can be given the most effective treatment.
Cancer is a genetic disease caused by mutations in our DNA. DNA damage occurs throughout life, both naturally and due to environmental factors. To cope with this, cells have evolved strategies to protect the integrity of the genetic code, but if mutations accumulate in key genes linked to cancer, tumours can develop.
Bowel cancer is the fourth most common cancer in the UK, with around 42,900 cases a year. Though still predominantly a cancer that affects older people, cases among the under 50s have been increasing in recent decades.
Disruption of DNA repair mechanisms is a major cause of increased cancer risk. About 20% of bowel cancers, known as mismatch repair deficient (MMRd) cancers, are caused by mutations in DNA repair genes. But disrupting these repair mechanisms is not entirely beneficial to tumours. Though they do allow tumours to develop, each mutation increases the risk that the body’s immune system will be triggered to attack the tumour.

Dr Marnix Jansen, senior author of the study from UCL Cancer Institute and UCLH, said: “Cancer cells need to acquire certain mutations to circumvent mechanisms that preserve our genetic code. But if a cancer cell acquires too many mutations, it is more likely to attract the attention of the immune system, because it’s so different from a normal cell.
“We predicted that understanding how tumours exploit faulty DNA repair to drive tumour growth — whilst simultaneously avoiding immune detection — might help explain why the immune system sometimes fails to control cancer development.”
In this study, researchers from UCL analysed whole genome sequences from 217 MMRd bowel cancer samples in the 100,000 Genomes Project database. They looked for links between the total number of mutations and genetic changes in key DNA repair genes.
The team identified a strong correlation between DNA repair mutations in the MSH3 and MSH6 genes, and an overall high volume of mutations.
The theory that these ‘flip-flop’ mutations in DNA repair genes might control cancer mutation rates was then validated in complex cell models, called organoids, grown in the lab from patient tumour samples.
Dr Suzanne van der Horst from University Medical Center Utrecht said: “Our study reveals that DNA repair mutations in the MSH3 and MSH6 genes act as a genetic switch that cancers exploit to navigate an evolutionary balancing act. On one hand, these tumours roll the dice by turning off DNA repair to escape the body’s defence mechanisms. While this unrestrained mutation rate kills many cancer cells, it also produces a few ‘winners’ that fuel tumour development.

“The really interesting finding from our research is what happens afterwards. It seems the cancer turns the DNA repair switch back on to protect the parts of the genome that they too need to survive and to avoid attracting the attention of the immune system. This is the first time that we’ve seen a mutation that can be created and repaired over and over again, adding it or deleting it from the cancer’s genetic code as required.”
The DNA repair mutations in question occur in repetitive stretches of DNA found throughout the human genome, where one individual DNA letter (an A, T, C or G) is repeated many times. Cells often make small copying mistakes in these repetitive stretches during cell division, such as changing eight Cs into seven Cs, which disrupts gene function.
Dr Hamzeh Kayhanian, first author of the study from UCL Cancer Institute and UCLH, said: “The degree of genetic disarray in a cancer was previously thought to be purely down to chance accumulation of mutations over many years. Our work shows that cancer cells covertly repurpose these repetitive tracts in our DNA as evolutionary switches to fine-tune how rapidly mutations accumulate in tumour cells.
“Interestingly, this evolutionary mechanism had previously been found as a key driver of bacterial treatment resistance in patients treated with antibiotics. Like cancer cells, bacteria have evolved genetic switches which increase mutational fuel when rapid evolution is key, for example when confronted with antibiotics. Our work thus further emphasises similarities between evolution of ancient bacteria and human tumour cells, a major area of active cancer research.”
The researchers say that this knowledge could potentially be used to gauge the characteristics of a patient’s tumour, which may require more intense treatment if DNA repair has been switched off and there is potential for the tumour to adapt more quickly to evade treatment — particularly to immunotherapies, which are designed to target heavily mutated tumours.
A follow-up study is already underway to find out what happens to these DNA repair switches in patients who receive cancer treatment.
Dr Hugo Snippert, a senior author of the study from University Medical Center Utrecht, said: “Overall our research shows that mutation rate is adaptable in tumours and facilitates their quest to obtain optimal evolutionary fitness. New drugs might look to disable this switch to drive effective immune recognition and, hopefully, produce better treatment outcomes for affected patients.”
This research was funded with grants from Cancer Research UK, the Rosetrees Trust, and Bowel Research UK.
Georgia Sturt, Research and Grants Manager at Bowel Research UK, said: “Cancer’s evasion of immune system destruction is a key element of its ability to grow and spread. Understanding exactly how bowel cancers do this is crucial to optimising treatment for patients. Bowel Research UK are delighted that our funding has contributed to producing this exciting new data, and we look forward to seeing how these discoveries could change treatments for future patients.”