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Breast Cancer

Mapping the Origins of Stomach Cancer: Uncovering Early Mutations and Risk Factors

Researchers have made significant advancements in understanding the earliest stages of stomach cancer, a leading cause of cancer-related deaths worldwide, through two recent innovative studies. With a prevalence rates particularly high in East Asia, including China, this cancer often stems from chronic inflammation caused by Helicobacter pylori infection, which affects approximately 15% of the Hong Kong population. This inflammation can lead to a pre-cancerous stage known as intestinal metaplasia. The innovative studies have uncovered crucial insights into the earliest changes in the stomach that contribute to the development of stomach cancer, laying the foundation for improved prevention and early detection, ultimately saving lives.

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The researchers at the Department of Pathology, School of Clinical Medicine at the LKS Faculty of Medicine of the University of Hong Kong (HKUMed) have made significant strides in understanding the earliest stages of stomach cancer, a leading cause of cancer-related deaths worldwide. Through two innovative studies, they have uncovered crucial insights into the early changes in the stomach that contribute to the development of stomach cancer, laying the foundation for improved prevention and early detection.

While the stomach’s acidic environment aids digestion, it can induce cancer-causing mutations in normal stomach tissues as individuals age. However, the timing and mechanisms of these early changes and how they promote the progression to cancer remain largely unknown. The HKUMed researchers provided valuable insights into these processes.

Mapping the Origins of Stomach Cancer

In a collaborative study, researchers from HKUMed, the Wellcome Sanger Institute, and the Broad Institute of MIT and Harvard analyzed genetic mutations in normal stomach lining tissue using advanced genome sequencing. For the first time, they sequenced whole genomes from 238 samples and performed targeted sequencing on an additional 829 samples from individuals with and without stomach cancer in Hong Kong, the US, and the UK.

The study revealed that despite the stomach’s harsh acidic environment, the stomach lining has protective mechanisms that prevent significant mutations. The researchers found that the number of mutations increases with age, with normal stomach glands accumulating approximately 28 mutations annually. In stomach cancer patients, the mutation rate is more than double, especially in the metaplastic glands.

Professor Leung Suet-yi, co-lead author of the research and Chairperson of the Department of Pathology, School of Clinical Medicine, HKUMed, said, “By age 60, nearly 10% of the stomach lining has mutations in known cancer genes, highlighting a gradual accumulation of potential cancer-causing changes over decades. The most surprising finding was that some stomach regions exhibited chromosome abnormalities linked to chronic inflammation.”

Risk Factors and Pre-cancer Model

The researchers identified risk factors for stomach cancer, including smoking, excessive alcohol drinking, a high salt diet, and a Helicobacter pylori infection. Professor Leung elaborated, “Our multinational team found that individuals with long-term stomach inflammation had significantly more mutations or extra chromosomes, indicating the potential role of inflammation in shaping a pre-cancer environment from an early age.”

World’s First Biobank of ‘Intestinal Metaplasia’ Organoid Models

In a related study, researchers from HKUMed and the InnoHK Centre for Oncology and Immunology investigated intestinal metaplasia (IM) in which stomach cells are transformed to resemble intestine cells. This transformation significantly increases the risk of developing stomach cancer, but the process remains poorly understood.

Co-led by Professor Helen Yan Hoi-ning, Assistant Professor in the Department of Pathology at HKUMed, and Professor Suet Yi Leung, the study used organoid culture to make a 3D model of IM. Organoids, tiny versions of organs grown in the lab from a patient’s tissue, provide a realistic model for studying the progression of IM to cancer.

The study revealed that IM organoids contain ‘hybrid’ cells with a mix of both stomach and intestinal characteristics. Typically associated with cancer cells, these traits facilitate tissue spread and make identifying early warning signs crucial. Professor Yan explained, “Using organoid technology, we can identify early changes when stomach cells become pre-cancerous.”

Harnessing Innovation for Early Detection and Prevention

By uncovering the earliest mutations and risk factors associated with stomach cancer and developing a sophisticated pre-cancer model, these studies offer invaluable insights for current prevention and early detection strategies. Professor Leung Suet-yi said, “With a living cell model now available, the potential for drug development to reverse IM becomes increasingly achievable.”

These breakthroughs provide new hope in the fight against stomach cancer, potentially transforming patient outcomes and clinical practices. The findings of these studies have significant implications for the prevention and early detection of stomach cancer, offering new avenues for research and treatment that can improve patient lives worldwide.

Breast Cancer

Early Cancer Detection: New Algorithms Revolutionize Primary Care

Two new advanced predictive algorithms use information about a person’s health conditions and simple blood tests to accurately predict a patient’s chances of having a currently undiagnosed cancer, including hard to diagnose liver and oral cancers. The new models could revolutionize how cancer is detected in primary care, and make it easier for patients to get treatment at much earlier stages.

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Early Cancer Detection: New Algorithms Revolutionize Primary Care

Two groundbreaking predictive algorithms have been developed to help General Practitioners (GPs) identify patients who may have undiagnosed cancer, including hard-to-detect liver and oral cancers. These advanced models use information about a patient’s health conditions and simple blood tests to accurately predict their chances of having an undiagnosed cancer.

The National Health Service (NHS) currently uses algorithms like the QCancer scores to combine relevant patient data and identify individuals at high risk of having undiagnosed cancer, allowing GPs and specialists to call them in for further testing. Researchers from Queen Mary University of London and the University of Oxford have created two new algorithms using anonymized electronic health records from over 7.4 million adults in England.

The new models are significantly more sensitive than existing ones, potentially leading to better clinical decision-making and earlier cancer diagnosis. Crucially, these algorithms incorporate the results of seven routine blood tests as biomarkers to improve early cancer detection. This approach makes it easier for patients to receive treatment at much earlier stages, increasing their chances of survival.

Compared to the QCancer algorithms, the new models identified four additional medical conditions associated with an increased risk of 15 different cancers, including liver, kidney, and pancreatic cancers. The researchers also found two additional associations between family history and lung cancer and blood cancer, as well as seven new symptoms of concern (itching, bruising, back pain, hoarseness, flatulence, abdominal mass, dark urine) associated with multiple cancer types.

The study’s lead author, Professor Julia Hippisley-Cox, said: “These algorithms are designed to be embedded into clinical systems and used during routine GP consultations. They offer a substantial improvement over current models, with higher accuracy in identifying cancers – especially at early, more treatable stages.”

Dr Carol Coupland, senior researcher and co-author, added: “These new algorithms for assessing individuals’ risks of having currently undiagnosed cancer show improved capability of identifying people most at risk of having one of 15 types of cancer based on their symptoms, blood test results, lifestyle factors, and other information recorded in their medical records.”

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Breast Cancer

Tailoring Bowel Cancer Surveillance for a Changing Healthcare Landscape

Australia’s recent move to lower the starting age for bowel (colorectal) cancer screening from 50 down to 45 years old will mean better outcomes — but it will also increase the burden on an already struggling healthcare system, warn researchers. They predict that the expanded screening program will likely lead to an influx of younger adults who will require ongoing surveillance with regular colonoscopies, prompting the team to review current clinical guidelines for at risk individuals.

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In a bid to improve bowel cancer outcomes, Australia has lowered its starting age for screening from 50 to 45 years old. While this move is expected to lead to better results, it will also put additional pressure on an already strained healthcare system.

Flinders University researchers have sounded the alarm, warning that the expanded screening program could lead to a surge in younger adults requiring ongoing surveillance with regular colonoscopies. In response, the team has reviewed current clinical guidelines for at-risk individuals and explored alternative approaches to better meet their needs.

A new study led by Flinders University reveals a shift in how bowel cancer surveillance might be approached using faecal tests. This approach could provide extra peace of mind for those at risk, particularly younger adults who are more concerned about bowel cancer despite it being traditionally viewed as an “older person’s disease”.

The researchers surveyed almost 300 people at risk for bowel cancer and found that most participants, regardless of age, wanted more frequent bowel cancer surveillance than what is currently recommended. A significant percentage preferred more frequent colonoscopies, with many supporting the incorporation of faecal tests between surveillance colonoscopies.

The study highlighted the role of fear in influencing surveillance preferences, with younger adults reporting higher levels of fear regarding bowel cancer and a preference for more frequent monitoring. This suggests that healthcare providers might want to consider this psychological aspect when providing care for younger adults at risk.

The researchers proposed adding faecal tests into existing colonoscopy-based surveillance protocols to allow for personalized strategies that extend the time between colonoscopies for those with negative results. Such an approach could meet the needs of patients wanting closer monitoring while also optimizing resource use in healthcare systems.

As early-onset bowel cancer continues to rise, this study reinforces the urgent need to adapt and update surveillance strategies to suit younger adults. Traditional guidelines often do not address the specific concerns and preferences of this demographic, which is becoming increasingly significant as screening eligibility ages are lowered.

By tailoring bowel cancer surveillance to individual needs, healthcare providers can improve patient outcomes while also optimizing resource use in a changing healthcare landscape.

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Breast Cancer

Breast Cancer Mortality Rates Decline Significantly Among Young Women Between 2010 and 2020

Breast cancer deaths among women ages 20-49 declined significantly between 2010 and 2020, according to a new study.

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The article highlights a substantial decrease in breast cancer deaths among young women between 2010 and 2020. Analyzing data from the Surveillance, Epidemiology, and End Results (SEER) registry, researchers found that incidence-based mortality declined from 9.70 per 100,000 women in 2010 to 1.47/100,000 in 2020 across all subtypes and racial/ethnic groups.

Luminal A had the most pronounced decline among the four subtypes, with a notable drop in 2017 (-32.88% annual percent change). Triple-negative breast cancer also showed a similar trend, with its largest decline in 2018 (-32.82% APC).

The analysis revealed that the declines became more pronounced after 2016, likely reflecting advancements in treatment options and greater access to care and screening. The study’s findings suggest that there are opportunities for further improvement, particularly in reducing disparities.

However, the research also identified some unexpected trends. Among women aged 20-39, luminal A had lower 10-year survival rates than luminal B, which was unexpected as luminal A is generally considered the least aggressive subtype with the most favorable prognosis.

The study’s limitations include a follow-up time limited to 10 years and a relatively smaller number of breast cancer deaths in some racial/ethnic groups. Despite these limitations, the research provides valuable insights into recent trends in mortality rates among young women and highlights the need for further investigation into understanding tumor biology and molecular mechanisms driving carcinogenesis and treatment response in younger women.

The article concludes by emphasizing the importance of continued research to ensure further reduction in breast cancer mortality, including research into population-based screening in women aged 40-49 and targeted screening in younger high-risk women. Additionally, it advocates for access to high-quality treatment and care for all women.

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