Tag: colorectal cancer

Categories : CancerTags :

Aspirin not a Quick Fix for Preventing Colorectal Cancer

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Photo by cottonbro studio

Daily aspirin use does not offer a quick or reliable way to prevent colorectal cancer in the general population and carries immediate risks of serious bleeding, a new Cochrane review finds. 

Colorectal cancer is one of the most common types of cancer worldwide. Prevention typically involves following a healthy lifestyle and periodically undergoing routine screening tests. In recent years, researchers have also explored the role of off-the-shelf medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), in reducing the incidence of colorectal cancer.

NSAIDs, which include ibuprofen and aspirin, are commonly used to reduce inflammation, fever, and pain. However, their role in the primary prevention of colorectal cancer remains uncertain and controversial.

Researchers from West China Hospital of Sichuan University in China analysed 10 randomised controlled trials including 124 837 participants, assessing whether aspirin or other NSAIDs could prevent colorectal cancer or precancerous polyps (adenomas) in people at average risk. The team found no suitable trials for non-aspirin NSAIDs, so their conclusions focus exclusively on aspirin.

Little to no short-term benefit and uncertain long-term effects

The review found that aspirin probably does not reduce the risk of colorectal cancer in the first 5 to 15 years of use. Possible protective effects after more than 10–15 years of follow-up were observed in some studies, but the certainty of this evidence is very low.

These potential long-term benefits come from observational follow-up phases of trials, in which participants may have stopped aspirin, started it independently, or begun other treatments, making the findings vulnerable to bias.

“While the idea of aspirin preventing bowel cancer in the long run is intriguing, our analysis shows that this benefit is not guaranteed and comes with immediate risks.”

— Dr Zhaolun Cai, lead author 

Immediate and well-established risks

The findings also show clear evidence that daily use of aspirin increases the risk of serious extracranial haemorrhage and probably increases the risk of haemorrhagic stroke. 

Although higher doses carry the greatest risk, low-dose (“baby”) aspirin also raises bleeding risk. Older adults and those with a history of ulcers or bleeding disorders may be particularly vulnerable.

The authors therefore caution that any potential long-term benefit must be weighed against the immediate and well-established risk of bleeding.
 

“My biggest worry is that people might assume that taking an aspirin today will protect them from cancer tomorrow. In reality, any potential preventive effect takes over a decade to appear, if it appears at all, while the bleeding risk begins immediately.”

— Dr Bo Zhang, senior author

Not a ‘one-size-fits-all’ solution

Previous evidence has shown potential benefits for people at high genetic risk of colorectal cancer, such as those with Lynch syndrome. However, this review focuses strictly on people at average risk, and the long-term evidence for them proved highly uncertain.

The authors urge that patients should not start taking aspirin for cancer prevention without a careful conversation with their healthcare professional about their personal risk of bleeding.
 

“This review reinforces that we must move away from a one-size-fits-all approach. Widespread aspirin use in the general population simply isn’t supported by the evidence. The future lies in precision prevention – using molecular markers and individual risk profiles to identify who might benefit most and who is most at risk.”

— Dr Dan Cao, senior author

The research team concludes that the story of aspirin for cancer prevention is far more complex than previously believed and that the balance of benefits and harms changes over time.

Dr Zhang adds:

“As scientists, we must follow the evidence where it leads. Our rigorous analysis of the highest-quality trials reveals that the ‘aspirin for cancer prevention’ story is more complex than a simple ‘yes or no.’ The current evidence does not support a blanket recommendation for aspirin use purely to prevent bowel cancer.” 

Read the review here.

Source: Cochrane

Categories : CancerTags :

How Does Lifetime Alcohol Consumption Affect Colorectal Cancer Risk?

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Results from a cancer screening trial indicate that consistent heavy alcohol intake and higher average lifetime drinking are associated with increased risk.

Photo by Apolo Photographer on Unsplash

Studies have demonstrated a link between alcohol consumption and an elevated risk of colorectal cancer. New research now reveals that higher lifetime alcohol consumption is also associated with a higher risk, especially for rectal cancer, and that quitting drinking can lower a person’s risk. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

When investigators analysed data on US adults enrolled in the National Cancer Institute (NCI) Prostate, Long, Colorectal, and Ovarian (PLCO) Cancer Screening Trial who did not have cancer at baseline, they observed that 1679 colorectal cancer cases occurred among 88 092 participants over 20 years of follow-up.

Current drinkers with an average lifetime alcohol intake of ≥ 14 drinks per week (heavy drinkers) had a 25% higher risk of developing colorectal cancer and a 95% higher risk of developing rectal cancer compared with those with an average lifetime alcohol intake of < 1 drink per week (light drinkers).

When further considering drinking consistency, heavy drinking throughout adulthood was linked to a 91% higher risk of colorectal cancer compared with consistent light drinking. In contrast, no evidence of increased colorectal cancer risk was observed among former drinkers, and former drinkers had lower odds of developing noncancerous colorectal tumours, or adenomas (which may go on to become cancerous) than current drinkers averaging < 1 drink per week, suggesting that alcohol cessation may lower individuals’ risks. These data were limited, however.

The association between alcohol consumption and increased risks observed in this and other studies might be explained by carcinogens produced from alcohol metabolism or alcohol’s effects on gut microbes. Additional studies are needed to test whether these mechanisms are involved.

“Our study is one of the first to explore how drinking alcohol over the life course relates to both colorectal adenoma and colorectal cancer risk. While the data on former drinkers were sparse, we were encouraged to see that their risk may return to that of the light drinkers,” said co–senior author Erikka Loftfield, PhD, MPH, of the NCI, part of the National Institutes of Health.

Source: Wiley

Categories : Cancer Diet and NutritionTags :

Sugary Drinks May Increase Risk of Metastasis in Advanced Colorectal Cancer

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A new study from researchers at The University of Texas MD Anderson Cancer Center shows that the glucose-fructose mix found in sugary drinks directly fuels metastasis in preclinical models of advanced colorectal cancer. The study was published in Nature Metabolism.

A research team led by Jihye Yun, PhD, assistant professor of Genetics, studied how sugary drinks may affect late-stage colorectal cancer. Using laboratory cancer models, they compared the effects of the glucose-fructose mix found in most sugary drinks with those of glucose or fructose alone. Only the sugar mix made cancer cells more mobile, leading to faster spread to the liver – the most common site of colorectal cancer metastasis.

The sugar mix activated an enzyme called sorbitol dehydrogenase (SORD), which boosts glucose metabolism and triggers the cholesterol pathway, ultimately driving metastasis. This is the same pathway targeted by statins, common heart drugs that inhibit cholesterol production. Blocking SORD slowed metastasis, even with the sugar mix present. These findings suggest that targeting SORD could also offer an opportunity to block metastasis.

“Our findings highlight that daily diet matters not only for cancer risk but also for how the disease progresses once it has developed,” Yun said. “While these findings need further investigation, they suggest that reducing sugary drinks, targeting SORD or repurposing statins may benefit patients with colorectal cancer.”

The Yun Laboratory is interested in studying how diet affects the intestine and cancer development, and they have made important discoveries on the impacts of sugary drinks on colorectal cancer.

Sugar has long been indirectly linked to an increase in cancer risk through obesity. However, a previous study by Yun’s lab challenged that view, showing that even moderate intake of sugary drinks directly fuelled tumour growth in early-stage colorectal cancer, independent of obesity. The current study was done to determine how sugary drinks may impact later-stage disease.

While this study needs further clinical investigation, the results suggest that reducing sugary drinks and targeting the SORD enzyme may offer opportunities to reduce colorectal cancer metastasis. Additional studies are warranted to confirm these results outside of preclinical models.

Further, Yun explained it may be worthwhile to consider revisions to current dietary recommendations to reduce sugary drink consumption in this patient population. To meet nutritional needs, many patients with cancer are encouraged to have nutritional supplement drinks and concentrated juices that contain high glucose and fructose content.

Source: The University of Texas MD Anderson Cancer Center

Categories : CancerTags :

Aspirin Found to Halve Recurrence for Certain Colorectal Cancers

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A Swedish-led research team at Karolinska Institutet and Karolinska University Hospital has shown in a new randomised clinical trial that a low dose of the well-known medicine aspirin halves the risk of recurrence after surgery in patients with colon and rectal cancer with a certain type of genetic alteration in the tumour.

Every year, nearly two million people worldwide are diagnosed with colorectal cancer, and 20–40% develop metastases.

Previous observational studies have suggested that aspirin may reduce the risk of certain cancers and possibly also the risk of recurrence after surgery in patients with colorectal cancer harbouring mutations in genes within the PIK3 signaling pathway. These genes regulate key cellular processes such as growth and division. When mutated, these processes can become dysregulated, leading to uncontrolled cell proliferation and cancer development.

Randomised clinical trials were lacking

Prior findings have been inconsistent and no randomised clinical trials had previously confirmed the association. To address this gap, the ALASCCA trial was initiated, with the results now been published in The New England Journal of Medicine.

The current study included more than 3500 patients with colon and rectal cancer from 33 hospitals in Sweden, Norway, Denmark, and Finland. Patients whose tumours showed a specific genetic mutation in the PIK3 signalling pathway – a mutation found in approximately 40% of patients – were randomised to receive either 160mg of aspirin daily or a placebo for three years after surgery.

For patients with the genetic mutation in PIK3, the risk of recurrence was reduced by 55% in those who received aspirin compared with the placebo group.

“Aspirin is being tested here in a completely new context as a precision medicine treatment. This is a clear example of how we can use genetic information to personalise treatment and at the same time save both resources and suffering,” says first author Anna Martling, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and senior consultant surgeon at Karolinska University Hospital.

Less favourable environment for cancer

So how does aspirin reduce the risk of recurrence of colon and rectal cancer? The researchers believe that the effect is likely due to aspirin acting through several parallel mechanisms – it reduces inflammation, inhibits platelet function and tumour growth. This combination makes the environment less favourable for cancer.

“Although we do not yet fully understand all the molecular links, the findings strongly support the biological rationale and suggest that the treatment may be particularly effective in genetically defined subgroups of patients,” says Anna Martling.

The researchers believe that the results could have global significance and influence treatment guidelines for colon and rectal cancer worldwide. Anna Martling sees the fact that the drug is well established as a major advantage.

“Aspirin is a drug that is readily available globally and extremely inexpensive compared to many modern cancer drugs, which is very positive,” says Anna Martling.

Source: Karolinska Institutet

Categories : Cancer Diet and NutritionTags :

Can Vitamin D Help Prevent Colorectal Cancer?

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The science is promising – but not straightforward

Photo by Michele Blackwell on Unsplash

Justin Stebbing, Anglia Ruskin University

The potential role of vitamin D in preventing and treating colorectal cancer (CRC) has attracted growing research interest – especially as CRC rates are rising, particularly among younger adults. This isn’t a new area of study. Low vitamin D levels have long been linked to a higher risk of developing colorectal cancer.

One large study involving over 12 000 participants found that people with low blood levels of vitamin D had a 31% greater risk of developing CRC compared to those with higher levels. Similarly, another study reported a 25% lower CRC risk among individuals with high dietary vitamin D intake.

Data from the Nurses’ Health Study – a long-term investigation of American nurses – showed that women with the highest vitamin D intake had a 58% lower risk of developing colorectal cancer compared to those with the lowest intake.

Now, a review highlights vitamin D’s promise in colorectal cancer prevention and treatment – but also underscores the complexity and contradictions in current research.

While observational data, which follow people’s use of vitamin D, and mechanistic studies, to investigate how vitamin D works in the laboratory, suggest protective effects, this isn’t confirmed by larger trials.

In fact, randomised controlled trials (RCTs), in which some people receive vitamin D and others don’t, the gold standard by which treatments are judged, reveal inconsistent outcomes. This highlights the need for a balanced approach to its integration into public health strategies.

Vitamin D is synthesised in the skin in response to sunlight and exerts its biological effects through vitamin D receptors (VDRs) found throughout the body, including in colon tissue. When activated, these receptors help regulate gene activity related to inflammation, immune response and cell growth – processes central to cancer development and progression.

Preclinical studies have shown that the active form of vitamin D (calcitriol) can suppress inflammation, boost immune surveillance (the immune system’s ability to detect abnormal cells), inhibit tumour blood vessel growth and regulate cell division – a key factor in cancer development, as demonstrated in my recent research.

Epidemiological studies, which track health outcomes across large populations over time, consistently find that people with higher blood levels of vitamin D have a lower risk of developing CRC. This paints a hopeful picture, suggesting that something as simple as getting more vitamin D – via sun exposure, diet, or supplements – could lower cancer risk.

But the story gets more complicated.

Mixed results

When it comes to medical decision-making, randomised controlled trials (RCTs) are the gold standard. These studies randomly assign participants to receive either a treatment (like vitamin D) or a placebo, helping eliminate bias and isolate cause-and-effect relationships.

Unfortunately, RCTs on vitamin D and CRC have produced mixed results.

For example, the VITAL trial – a major RCT involving over 25 000 participants – found no significant reduction in overall colorectal cancer incidence with 2000 IU/day of vitamin D supplementation over several years.

However, a meta-analysis of seven RCTs did show a 30% improvement in CRC survival rates with vitamin D supplements, suggesting potential benefits later in the disease course rather than for prevention.

On the other hand, the Vitamin D/Calcium Polyp Prevention Trial found no reduction in the recurrence of adenomas (pre-cancerous growths) with supplementation, raising questions about who benefits most, and at what dosage.

Adding to the uncertainty is the question of causation. Does low vitamin D contribute to cancer development? Or does the onset of cancer reduce vitamin D levels in the body? It’s also possible that the observed benefits are partly due to increased sunlight exposure, which itself may have independent protective effects.

The big picture

These discrepancies highlight the importance of considering the “totality of evidence” – treating each study as one piece of a larger puzzle.

The biologic plausibility is there. Observational and mechanistic studies suggest a meaningful link between vitamin D and lower CRC risk. But the clinical evidence isn’t yet strong enough to recommend vitamin D as a standalone prevention or treatment strategy.

That said, maintaining sufficient vitamin D levels – at least 30ng/mL – is a low-risk, cost-effective health measure. And when combined with other strategies like regular screening, a healthy diet, physical activity, and personalised care, vitamin D could still play a valuable role in overall cancer prevention.

Vitamin D is not a miracle cure – but it is part of a much broader picture. Its role in colorectal cancer is promising but still being defined. While it’s not time to rely on supplements alone, ensuring adequate vitamin D levels – through sun exposure, diet, or supplements – remains a smart choice for your health.

Colorectal cancer is a complex disease, and tackling it requires an equally nuanced approach. For now, that means focusing on evidence-based lifestyle changes, regular screenings, and staying informed as new research unfolds.

Justin Stebbing, Professor of Biomedical Sciences, Anglia Ruskin University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : Cancer GastrointestinalTags :

Low-carb Diet’s Colorectal Cancer Risk is Mediated by the Gut Microbiome

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Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

Researchers from the University of Toronto have shown how a low-carbohydrate diet can worsen the DNA-damaging effects of some gut microbes to cause colorectal cancer.

The study, published in the journal Nature Microbiology, compared the effects of three different diets: normal, low-carb, or Western-style with high fat and high sugar, each in combination with specific gut bacteria on colorectal cancer development in mice.

They found that a unique strain of E. coli bacteria, when paired with a diet low in carbs and soluble fibre, drives the growth of polyps in the colon, which can be a precursor to cancer.

“Colorectal cancer has always been thought of as being caused by a number of different factors including diet, gut microbiome, environment and genetics,” says senior author Alberto Martin, a professor of immunology at U of T’.

“Our question was, does diet influence the ability of specific bacteria to cause cancer?”

To answer this question, the researchers, led by postdoctoral fellow Bhupesh Thakur, examined mice that were colonized with one of three bacterial species that had been previously linked to colorectal cancer and fed either a normal, low-carb or Western-style diet.

Only one combination, a low-carb diet paired with a strain of E. coli that produces the DNA-damaging compound colibactin, led to the development of colorectal cancer.

The researchers found that a diet deficient in fibre increased inflammation in the gut and altered the community of microbes that typically reside there, creating an environment that allowed the colibactin-producing E. coli to thrive.

They also showed that the mice fed a low-carb diet had a thinner layer of mucus separating the gut microbes from the colon epithelial cells. The mucus layer acts as a protective shield between the bacteria in the gut and the cells underneath. With a weakened barrier, more colibactin could reach the colon cells to cause genetic damage and drive tumour growth. These effects were especially strong in mice with genetic mutations in the mismatch repair pathway that hindered their ability to fix damaged DNA.

While both Thakur and Martin emphasize the need to confirm these findings in humans, they are also excited about the numerous ways in which their research can be applied to prevent cancer.

Defects in DNA mismatch repair are frequently found in colorectal cancer, which is the fourth most commonly diagnosed cancer in Canada. An estimated 15 per cent of these tumours having mutations in mismatch repair genes. Mutations in these genes also underlie Lynch syndrome, a genetic condition that significantly increases a person’s risk of developing certain cancers, including colorectal cancer.

“Can we identify which Lynch syndrome patients harbour these colibactin-producing microbes?” asks Martin. He notes that for these individuals, their findings suggest that avoiding a low-carb diet or taking a specific antibiotic treatment to get rid of the colibactin-producing bacteria could help reduce their risk of colorectal cancer.

Martin points out that a strain of E. coli called Nissle, which is commonly found in probiotics, also produces colibactin. Ongoing work in his lab is exploring whether long-term use of this probiotic is safe for people with Lynch syndrome or those who are on a low-carb diet.

Thakur is keen to follow up on an interesting result from their study showing that the addition of soluble fibre to the low-carb diet led to lower levels of the cancer-causing E. coli, less DNA damage and fewer tumours.

“We supplemented fibre and saw that it reduced the effects of the low-carb diet,” he says. “Now we are trying to find out which fibre sources are more beneficial, and which are less beneficial.”

To do this, Thakur and Martin are teaming up with Heather Armstrong, a researcher at the University of Alberta, to test whether supplementation with a soluble fibre called inulin can reduce colibactin-producing E. coli and improve gut health in high-risk individuals, like people with inflammatory bowel disease.

 “Our study highlights the potential dangers associated with long-term use of a low-carb, low-fibre diet, which is a common weight-reducing diet,” says Martin.

“More work is needed but we hope that it at least raises awareness.”

Source: University of Toronto

Categories : Cancer GastrointestinalTags :

Scientists Find a Molecule that Promotes Gut Healing and Stifles Tumour Growth

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

Researchers at Karolinska Institutet have found a molecule that can both help the intestines to heal after damage and suppress tumour growth in colorectal cancer. The discovery could lead to new treatments for inflammatory bowel disease (IBD) and cancer. The results are published in the journal Nature.

Many patients with inflammatory bowel disease (IBD) such as Crohn’s disease or ulcerative colitis do not respond to available treatments, highlighting the need to identify novel therapeutic strategies. In this study, researchers propose that promoting mucosal healing through tissue regeneration could be a valid alternative to immunosuppressive drugs.  

“However, it’s virtually impossible to promote tissue regeneration without the risk of inducing tumour growth, as cancer cells can hijack the body’s natural healing processes and start to grow uncontrollably,” says lead author Srustidhar Das, research specialist in Eduardo Villablanca’s research group at Karolinska Institutet. “We’ve now identified a molecule that can help the intestines to heal after damage while suppressing tumour growth in colorectal cancer.” 

New drug candidates 

In their search for new ways to treat IBD, the researchers have identified a handful of molecules with drug-candidate potential. They found that activation of a protein called the Liver X receptor (LXR) can promote regeneration and suppress tumour growth in colorectal cancer. 

“The discovery of both these functions was astonishing,” says last author Eduardo J. Villablanca, docent at Karolinska Institutet. “We now need to study how LXR controls tumour formation more closely.” 

The researchers used a collection of advanced technologies to conduct their study, which included mapping the transcriptome of intestinal cells. The researchers also cultivated what are known as 3D organoids: small, three-dimensional cell structures that mimic the function and structure of the body’s own organs, albeit in miniature format. 

They then used spatial transcriptomics to map the gene expression in the different tissues, a technique that has been developed at SciLifeLab by scientists from the Royal Institute of Technology (KTH) and Karolinska Institutet in Sweden. 

Third most common cancer 

Patients, the third most common type in Sweden, are often treated with chemotherapy and radiotherapy, but this can cause irritation and swelling of the bowel mucosa with subsequent chronic intestinal inflammation. 

“Thus, this new therapeutic molecule has the potential to treat not only IBD patients but also cancer patients to prevent chronic bowel disorders after radiotherapy and/or chemotherapy,” says Eduardo J. Villablanca. 

Source: Karolinska Institutet

Categories : Cancer New Compounds and TreatmentsTags :

Crop-destroying Fungus Yields a Potential Colorectal Cancer Treatment

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Plant fungus provides new drug with a new cellular target

Human colon cancer cells. Credit: National Cancer Institute

Novel chemical compounds from a fungus could provide new perspectives for treating colorectal cancer, one of the most common and deadliest cancers worldwide. The fungus, Bipolaris victoriae, is otherwise known as a fungal plant pathogen which in the 1940s caused the “Victoria blight”, decimating oats and similar grains in the US.

In the journal Angewandte Chemie, researchers reported on the isolation and characterisation of a previously unknown class of metabolites (terpene-nonadride heterodimers). One of these compounds effectively kills colorectal cancer cells by attacking the enzyme DCTPP1, which thus may serve as a potential biomarker for colorectal cancer and a therapeutic target.

Rather than using conventional cytostatic drugs, which have many side effects, modern cancer treatment frequently involves targeted tumour therapies directed at specific target molecules in the tumour cells. The prognosis for colorectal cancer patients remains grim however, demanding new targets and novel drugs.

Targeted tumour therapies are mostly based on small molecules from plants, fungi, bacteria, and marine organisms. About half of current cancer medications were developed from natural substances. A team led by Ninghua Tan, Yi Ma, and Zhe Wang at the China Pharmaceutical University (Nanjing, China) chose to use Bipolaris victoriae S27, a fungus that lives on plants, as the starting point in their search for new drugs.

The team first analysed metabolic products by cultivating the fungus under many different conditions (OSMAC method, one strain, many compounds). They discovered twelve unusual chemical structures belonging to a previously unknown class of compounds: terpene-nonadride heterodimers, molecules made from one terpene and one nonadride unit. Widely found in nature, terpenes are a large group of compounds with very varied carbon frameworks based on isoprene units. Nonadrides are nine-membered carbon rings with maleic anhydride groups. The monomers making up this class of dimers termed “bipoterprides” were also identified and were found to contain additional structural novelties (bicyclic 5/6-nonadrides with carbon rearrangements).

Nine of the bipoterprides were effective against colorectal cancer cells. The most effective was bipoterpride No. 2, which killed tumour cells as effectively as the classic cytostatic drug Cisplatin. In mouse models, it caused tumours to shrink with no toxic side effects.

The team used a variety of methods to analyse the drug’s mechanism: bipoterpride 2 inhibits dCTP-pyrophosphatase 1 (DCTPP1), an enzyme that regulates the cellular nucleotide pool. The heterodimer binds significantly more tightly than each of its individual monomers. The activity of DCTPP1 is elevated in certain types of tumours, promoting the invasion, migration, and proliferation of the cancer cells while also inhibiting programmed cell death. It can also help cancer cells to resist treatment. Bipoterpride 2 inhibits this enzymatic activity and disrupts the now pathologically altered amino acid metabolism in the tumour cells.

The team was thus able to identify DCTPP1 as a new target for the treatment of colorectal cancer and bipoterprides as new potential drug candidates.

Source: Wiley

Categories : Cancer Diet and NutritionTags :

Study Reveals Diet is the Main Risk Factor for Colon Cancer in Younger Adults

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Photo by Alex Haney

A new Cleveland Clinic study has identified diet-derived molecules called metabolites as main drivers of young-onset colorectal cancer risk, especially those associated with red and processed meat. The NPJ Precision Oncology report, which analysed metabolite and microbiome datasets, highlighted that one of the best ways a younger ( < 60 years) adult can prevent colorectal cancer is to discuss their diet with their doctor.

Increased monitoring and screening for colorectal cancer is an extremely helpful tool. Despite the success of these methods, these data indicate physicians can take a different approach with their younger patients, says senior author and gastrointestinal oncologist Suneel Kamath,MD.

“At the end of the day, it’s impractical to apply our care models for those over 60 to younger adults simply because we cannot give everyone in the system yearly colonoscopies,” he explains. “What is much more feasible is to give everyone in the system a simple test to measure a biomarker that determines their colorectal cancer risk. Then we can give the most at-risk individuals appropriate screening.”

Former clinical fellow Thejus Jayakrishnan, MD, and Naseer Sangwan, PhD, director of the Microbial Sequencing & Analytics Resource Core co-led the work. Researchers in Cleveland Clinic’s Center for Young-Onset Colorectal Cancer provided large-scale analyses of patient data from individuals who received care for either young- or average-onset colorectal cancer at Cleveland Clinic.

One previous study from this team identified differences in the metabolites (diet-derived molecules) of young – versus average-onset colorectal cancer, while another identified differences in gut microbiome between younger and older adults with colorectal cancer. These studies provided many potential directions for studying young-onset CRC. However, when more factors are involved in cancer risk, it becomes more complicated to understand what’s going on and plan future research, Dr Sangwan says. Interactions between these factors, like when our gut bacteria consume our metabolites and produce their own, make it even more complex.

Dr Sangwan and his team then developed an AI algorithm to combine and analyse the existing studies’ datasets and clarify what factors are most relevant for future study. Surprisingly, Dr Sangwan’s analysis revealed that differences in diet (identified through analysing metabolites) accounted for a significant proportion of the differences observed between the young-onset and older-onset patients.

“Researchers – ourselves included – have begun to focus on the gut microbiome as a primary contributor to colon cancer risk. But our data clearly shows that the main driver is diet,” Dr Sangwan says. “We already know the main metabolites associated with young-onset risk, so we can now move our research forward in the correct direction.”

The team was excited to see diet play such a large role in cancer risk, because it is much easier to identify at-risk patients by counting the metabolites in their blood than it is to sequence the bacterial DNA in their stool for different microbes.

“It can actually be very complicated and difficult to change your microbiome,” explains Dr Kamath. “While it’s not always easy, it is much simpler to change your diet to prevent colon cancer.”

Addressing factors in our diet to prevent colon cancer

Younger colon cancer patients had higher levels of metabolites associated with the production and metabolism of an amino acid called arginine, and with the urea cycle compared to their older peers. These differences may be tied to long-term consumption of red meat and processed meat. The team is now analyzing national datasets to validate their Cleveland Clinic-specific findings in patients across the country.

After they show that arginine and urea cycle metabolites (and, by proxy, red and processed meat overconsumption) are elevated across younger adults with colon cancer nationwide, they plan to test whether certain diets or commercially available drugs that regulate arginine production and the urea cycle can help prevent or even treat young-onset colorectal cancer.

Dr Kamath says that even though more research is needed to understand exactly how dietary factors cause colon cancer, his current findings have already changed the way he delivers patient care.

“Even though I knew before this study that diet is an important factor in colon cancer risk, I didn’t always discuss it with my patients during their first visit. There is so much going on, it can already be so overwhelming,” says Dr Kamath. “Now, I always make sure to bring it up to my patients, and to any healthy friends or family members they may come in with, to try and equip them with the tools they need to make informed choices about their lifestyle.”

Source: Cleveland Clinic

Categories : Cancer TransplantsTags :

Transplant Beats Other Therapies for Colorectal Cancer Metastasised to the Liver

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Human colon cancer cells. Credit: National Cancer Institute

Colorectal cancer often metastasises to the liver, and for some patients, surgical removal of their liver tumours is not an option. A new study led by researchers at the Wilmot Cancer Institute and University of Rochester Medical Center (URMC) shows that a select group of patients with colorectal cancer that has spread to the liver tend to fare better if they receive a liver transplant as opposed to other common therapies.

In the study, published in JAMA Surgery, patients who had liver transplants tended to live longer without cancer progression than patients who opted for other treatments. While previous studies have shown the benefits of liver transplants for these patients, this is the first study to compare liver transplants to other treatment options.

“In any cancer treatment, it’s very easy to describe the outcomes of the patients who received the intervention, but similar patients that did not undergo the intervention can serve as a good comparison,” said Matthew Byrne, MD, a surgery resident at URMC and author of the study. “Without randomised, controlled trial data, this study offers the best evidence that is available to understand whether liver transplant provides better outcomes over other treatments.”

The study followed 33 patients whose colorectal cancer was under control, but who had liver tumours that could not be surgically removed. All 33 patients were eligible for liver transplantation, but only 20 chose to have a transplant, while 13 opted for other classical therapies, like removal of part of the liver, chemotherapy, or liver-directed therapies.

Compared to the classical therapy group, the liver transplant group had significantly higher progression-free survival rates across three years of follow-up. One year after liver transplant, 90% of patients showed no signs of cancer progression. That number dropped to 73% after two years and to 36% at three years. On the other hand, only 42% of patients who opted for other therapies were cancer-progression-free after one year, which dropped to roughly 10% after two and three years.

The transplant group also had higher overall survival rates than the standard therapy group, though the difference wasn’t statistically significant. At the three-year follow-up, 90% of transplant patients had survived, compared to 73% of patients who received other therapies.

Though this study provides solid evidence, larger clinical trials will be needed to fully understand the added benefit of liver transplant compared to other treatments for these patients, and to better refine which patients benefit most.

Source: University of Rochester Medical Center