Black women experience disproportionately elevated risks of developing and dying from early-onset breast cancer. New research published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society, reveals the genes that are most likely to be mutated to contribute to these increased risks.
In the study of 686 young Black women diagnosed in Florida and Tennessee with invasive breast cancer at age 50 or younger in 2005–2018, genetic testing showed that 15.3% of the women carried a gene variant with a suspected link to breast and/or ovarian cancer, with most occurring in the BRCA1 and BRCA2 genes and fewer in PALB2, ATM, and other genes. A family history of breast cancer was common in women with mutations in BRCA1, BRCA2, and PALB2. Triple-negative breast cancers (one of the most aggressive forms) were most often seen in women with BRCA1 mutations. Also, most of the women with BRCA1 mutations were diagnosed at or below age 40, whereas the age at diagnosis was more evenly distributed up to age 50 for women with variants in the other genes.
The study’s findings point to the importance of breast cancer genetic testing for young Black women, a group that is less likely to receive such screening compared with other racial and ethnic groups. Such tests could identify women most likely to benefit from more frequent screening and preventive measures to safeguard their health.
“We must test at-risk women across all populations – testing is essential to personalise treatment strategies and enable life-saving prevention for future cancers, and it may empower at-risk family members to get tested so they too can benefit from this information,” said senior author Tuya Pal, MD, of Vanderbilt University Medical Center. “Equitable access to inherited cancer testing ensures that all women, regardless of race, can benefit from precision medicine and take control of their genetic health.”
The findings build on decades of scientific understanding by revealing an additional pathway the kidney uses to control water balance. Until now, the body’s ability to concentrate urine – and prevent dehydration – has been thought to depend primarily on the hormone vasopressin. Dr Chebib’s team discovered an alternative mechanism that operates independently of that system.
“The kidney’s ability to regulate water is one of the most fundamental processes in the body,” Dr Chebib says. “It’s not every day that you uncover a new way it carries out that function.”
Polycystic kidney disease is a common inherited condition that causes fluid-filled cysts to grow in the kidneys over time, gradually reducing kidney function and often leading to kidney failure. It affects millions of people worldwide, including an estimated 140 000 people in the US with the most common form, autosomal dominant PKD (ADPKD). Many patients eventually require dialysis or a kidney transplant.
Dr Chebib’s team studies how kidney cysts grow in PKD using lab-grown cell models. As part of that work, they tested compounds expected to worsen the disease process by increasing cellular signals linked to cyst growth. One of those compounds was probenecid, a drug first used in the 1940s to conserve limited supplies of penicillin by reducing its urinary excretion.
“We thought this drug would make the disease process worse,” Dr Chebib says. “Instead, it did the opposite.”
Rather than promoting cyst growth, the drug slowed it. After repeating the experiments multiple times, the team realised they had uncovered something important.
Further investigation revealed that probenecid affects how kidney cells handle urate, a molecule commonly associated with gout. Inside the cell, urate acts as a signal – triggering a chain of events that helps move water channels to the cell surface. This allows the kidney to reabsorb water and concentrate urine without relying on vasopressin, the hormone traditionally thought to control this process.
“This represents a distinct pathway from what is described in traditional physiology models,” Dr Chebib says. “It demonstrates that the kidney has an additional mechanism to preserve water.”
For patients with PKD, the discovery could address one of the biggest challenges of current treatment. The only approved therapy, tolvaptan, works by blocking vasopressin, which slows cyst growth but causes patients to produce very large amounts of urine – often 6 to 7 litres a day. That side effect can be difficult to live with and leads some patients to stop treatment.
In preclinical studies and a small clinical trial, adding probenecid reduced urine volume and nighttime urination while preserving the treatment’s effectiveness.
After taking probenecid, patients’ urine volume dropped by about 30% on average, and they went from waking up several times a night to urinate to about once per night. Many also reported improved quality of life.
“The goal is to preserve the therapeutic benefit of tolvaptan while reducing its burden,” Dr. Chebib says.
Despite these promising results, researchers are not planning to rely on probenecid as a long-term solution. The drug is decades old, affects multiple systems in the body and is not widely available today. Instead, the team is using what they learned to design more targeted therapies.
“Probenecid helped us uncover the mechanism,” Dr Chebib says. “Our goal is to take this insight and develop therapies designed specifically for this pathway.”
For Dr Chebib, the work is rooted in early inspiration. He was drawn to kidney research after his father developed PKD.
“This has been a long and deeply purposeful journey,” he says. “It started with a personal motivation and led to something that could ultimately benefit patients.”
For a complete list of authors, disclosures and funding, see the study.
Study provides much-needed benchmark with finding that alcohol consumption is associated with increased risk above one drink per day for both men and women
Photo by Pavel Danilyuk on Pexels
Even what many consider to be moderate drinking is linked to an increased risk of death, disability, and chronic diseases such as cancer and heart disease, according to a new study published in the Journal of Studies on Alcohol and Drugs.
“This study provides the most comprehensive US estimates to date of lifetime risks of alcohol-attributable mortality and morbidity, showing that even moderate levels of consumption increase the risk of premature death and disability,” said study co-author Katherine M. Keyes, PhD, professor of Epidemiology at Columbia University Mailman School of Public Health. “No protective effect of drinking was observed even at low levels,” noted Keyes, whose research focuses on alcohol use and other substances epidemiology across the life course.
The findings show mortality risk from alcohol of 1 in 25 for people who consumed an average of 14 drinks per week. In contrast, drinking up to 7 drinks per week was associated with only minimally elevated risks for most conditions.
“Even low levels of alcohol use come with health risks,” says first study author Kevin Shield, PhD, an associate professor at the University of Toronto and a senior scientist who leads the World Health Organization (WHO)/Pan American Health Organization (PAHO) Collaborating Centre in Addiction and Mental Health. “And that risk continues to increase the more someone drinks.”
The researchers, from the United States and Canada, aimed to estimate how lifetime drinking habits affect Americans’ risk of illness and death related to alcohol. After medical experts reviewed more than 7200 scientific articles on alcohol-related diseases and injuries to determine the level of risk for each condition, the researchers applied those risks to large national health data sets. They then used statistical modelling to estimate how different drinking levels influence long-term health outcomes.
The study offers more concrete guidance than the new US Dietary Guidelines, which currently advise Americans to “limit alcoholic beverages” without specifying how much alcohol is safe to drink. Previous guidelines recommended a daily limit of two alcoholic drinks for men and one for women. The definition of a ‘drink’ varies by beverage type, typically 12 ounces (340mL) for beer, 5 ounces (140mL) for wine, and 1.5 ounces (40mL)for spirits, although that too can vary by alcohol concentration.
While the new US Dietary Guidelines contain a useful ‘less-is-best’ message, they provide no quantitative framework, according to the authors. This study was designed to do just that across the drinking spectrum.
It turns out that an average of two drinks per day, which might be considered ‘moderate’ from a social standpoint, is associated with a substantially elevated risk of a premature death caused by alcohol, they explain.
In addition to mortality risk, researchers examined how drinking patterns influence chronic and acute alcohol-related conditions such as cancer – including oesophageal, oral, and breast – cardiovascular disease, liver disease, and injury.
The study overturns a common misconception that alcohol can protect health. The researchers did not observe a significant protective effect of alcohol on overall health at any level of consumption. They noted that at low levels, alcohol may be associated with a reduced risk of ischemic heart disease and stroke. But when you look across the full range of health outcomes, including cancer and other chronic diseases, those potential benefits are outweighed by the risks even at 7 drinks per week.
Statistical modelling used in the study to determine health risks was based on “the best possible data,” according to the team. But they caution one should not assume that means one person’s individual health risk is the same as what is reported here – that depends on other factors like lifestyle, genetics, drinking patterns, and other choices that differ person to person.
The researchers estimated risk for all health conditions known to be causally related to alcohol and then aggregated these estimates to determine the total health risk. Yet, new research continues to emerge that links alcohol with additional health conditions, such as pancreatic cancer. “Understanding those relationships, and how much alcohol contributes to those risks, is an area that still needs further work,” says Keyes and Shield.
By finding that alcohol consumption is associated with increased risk above one drink per day for both men and women, the study offers a much-needed benchmark.
“Having a clearer threshold helps people better understand what level of drinking is associated with increased risk and make more informed decisions when drinking.”
In an accompanying editorial, Robert M. Vincent, a former associate administrator for the US Substance Abuse and Mental Health Services Administration, discusses his view of the behind-the-scenes environment in which the study was produced. “The Alcohol Intake and Health report was explicitly invited to inform alcohol guidance during development of the Dietary Guidelines for Americans, 2025–2030,” he writes. “Despite the study’s adherence to its mandate, its findings were sidelined.”
See the paper for a full list of co-authors and their institutions.
When it comes to autism, few questions spark as much debate as how best to support autistic people with the greatest needs.
This prompted The Lancet medical journal to commission a group of international experts to propose a new category of “profound autism”.
This category describes autistic people who have little or no language (spoken, written, signed or via a communication device), who have an IQ of less than 50, and who require 24-hour supervision and support.
It would only apply to children aged eight and over, when their cognitive and communication abilities are considered more stable.
In our new study, we considered how the category could impact autism assessments. We found 24% of autistic children met, or were at risk of meeting, the criteria for profound autism.
Why the debate?
The category is intended to help governments and service providers plan and deliver supports, so autistic people with the highest needs aren’t overlooked. It also aims to re-balance their under-representation in mainstream autism research.
This new category may be helpful for advocating for a greater level of support, research and evidence for this group.
But some have raised concerns that autistic people who don’t fit into this category could be perceived as less in need and excluded from services and funding supports.
Others argue the category doesn’t sufficiently emphasise autistic people’s strengths and capabilities, and places too much emphasis on the challenges that are experienced.
What did we do?
We conducted the first Australian study to examine how the “profound autism” category might apply to children attending publicly funded diagnostic services for developmental conditions.
Drawing on the Australian Child Neurodevelopment Registry, we examined data from 513 autistic children assessed between 2019 and 2024. We asked:
how many children met the criteria for profound autism?
were there behavioural features that set this group apart?
Because we focused on children at the time of diagnosis, most (91%) were aged under eight years. We described these children as being “at risk of profound autism”.
What did we find?
Around 24% of autistic children in our study met, or were at risk of meeting, the criteria for profound autism. This is similar to the proportion of children internationally.
Almost half (49.6%) showed behaviours that were a safety risk, such as attempting to run away from carers, compared with one-third (31.2%) of other autistic children.
These challenges weren’t limited to children who met criteria for profound autism. Around one in five autistic children (22.5%) engaged in self-injury, and more than one-third (38.2%) showed aggression toward others.
So, while the category identified many children with very high needs, other children who didn’t meet these criteria also had significant needs.
Importantly, we found the definition of “profound autism” doesn’t always line up with the official diagnostic levels which determine the level of support and NDIS funding children receive.
In our study, 8% of children at risk of profound autism were classified as level 2, rather than level 3 (the highest level of support). Meanwhile, 17% of children classified as level 3 did not meet criteria for profound autism.
Our concern
We looked at children when they first received an autism diagnosis. Children were aged 18 months to 16 years, with more than 90% under the age of eight years.
This aligns with our earlier research, showing the average age of diagnosis in public settings is 6.6 years.
From a practical perspective, our biggest concern about the profound autism category is the age threshold of eight years.
Because most children are already assessed before age eight, introducing this category into assessment services would mean many families would need repeat assessments, placing additional strain on already stretched developmental services.
Second, modifications will be needed if this criteria is going to be used to inform funding decisions as it didn’t map perfectly onto level 3 support criteria.
On balance, however, our results suggest the profound autism category may provide a clear, measurable way to describe the needs of autistic people with the highest support requirements.
Every autistic child has individual strengths and needs. The term “profound autism” would need to be promoted with inclusive and supportive language, so as to not replace or diminish individual needs, but to help clinicians tailor supports and obtain additional resources when needed.
If you’re concerned your child requires substantial support, here are some practical steps you can take to ensure their needs are recognised and addressed:
Explain your concerns
Not all clinicians have experience working with children with high support needs. Be as clear as possible about behaviours that affect your child’s safety or daily life, including self-injury, aggression or attempts to run away. These details, while difficult to share, help give a clearer picture of your child’s support needs.
It can also be a challenge to find and access clinicians with appropriate expertise. Another potential benefit of having a defined category is that it can better help families navigate care.
Ask about support for the whole family
Our studies show that many caregivers want more support for themselves but don’t always ask. Talk with clinicians about supports for yourself as well, including respite, or family support groups.
Reach out
Coming together with other carers and families can reduce your own isolation and normalise many of the unique challenges you face. Connecting with like-minded people can provide a supportive, empathetic and empowering community.
Plan for safety
For children with high support needs, prioritise safety planning with your child’s care team. This can include strategies to reduce risks, as well as planning how best to support your child’s interactions with health, education and disability services over time.
