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Study unveils many ways carcinogens trigger development of breast cancer

Because only 5 to 10 percent of breast cancers are due to high risk inherited mutations, such as BRCA1 and BRCA2, scientists say a better understanding of how environmental factors contribute to the disease is needed to prevent future breast cancers and lower incidence rates.

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In the most comprehensive review to date of how breast cancer develops, scientists have created a detailed map that describes the many ways in which environmental chemicals can trigger the disease. Using ionizing radiation as a model, the researchers identified key mechanisms within cells that when disrupted cause breast cancer. Because the findings can be generalized to other environmental carcinogens, they could help regulators identify chemicals that increase breast cancer risk.

“We know exposure to toxic chemicals can play an important role in the development of breast cancer,” says Ruthann Rudel, an environmental toxicologist at Silent Spring Institute and one of the study’s co-authors. “Yet, when regulators try to evaluate whether a chemical is harmful or not, the tests they use do not capture the effects on the breast. This gap in testing means potential breast carcinogens are being given the green light for use in our consumer products.”

Breast cancer is the most common invasive cancer in women, with incidence rates highest in North America and Europe, and rates increasing globally. Because only 5 to 10 percent of breast cancers are due to high risk inherited mutations, such as BRCA1 and BRCA2, scientists say a better understanding of how environmental factors contribute to the disease is needed to prevent future breast cancers and lower incidence rates.

Toward that end, researchers at Silent Spring looked at ionizing radiation–an established risk factor for breast cancer. People can be exposed to ionizing radiation from many sources, including X-rays, CT scans and radiation treatment. The effects of radiation on breast cancer have been extensively studied, based in large part on studies of survivors of the atomic bombings in Hiroshima and Nagasaki and women who were exposed to medical radiation as adolescents.

Reporting in the journal Archives of Toxicology, Rudel and co-author Jessica Helm reviewed 467 studies to identify the sequence of biological changes that occur in breast cells and tissue from the time of radiation exposure to the formation of a tumor. They then created a map of these sequential changes, revealing multiple interconnected pathways by which ionizing radiation leads to breast cancer.

The researchers created the map using a framework called an Adverse Outcome Pathway (AOP). AOPs were designed by the Organisation for Economic Co-operation and Development (OECD) as a way to represent how complex diseases develop, and to help regulators, chemical manufacturers, and drug companies predict how chemicals might affect diseases early in the research process.

“It turns out, not surprising, breast cancer is a lot more complex than how it’s conveyed in traditional cancer models,” says Rudel. In traditional models, ionizing radiation triggers breast cancer solely through DNA damage. The new model by Silent Spring integrates recent findings in cancer biology that show radiation, in addition to DNA damage, also increases the production of molecules called reactive oxygen and nitrogen species. These molecules wreak havoc inside cells, causing inflammation, altering DNA, and disrupting other important biological activities.

“This study is important and highlights the need for a holistic consideration of mechanistic evidence when identifying potential carcinogens,” says Kathryn Guyton, a senior toxicologist at the International Agency for Research on Cancer. “In reality there are multiple key characteristics of carcinogens. Increasingly, we are appreciating that human carcinogens may exhibit different combinations of these key characteristics.”

The Silent Spring team also found that the biological changes that lead to breast cancer are highly influenced by reproductive hormones, such as estrogen and progesterone. Reproductive hormones stimulate the proliferation of cells within the breast, so chemicals that similarly encourage cell proliferation could make the breast more susceptible to tumors. “Critical periods of development, such as during puberty or pregnancy when the breast undergoes important changes, are times when the breast is especially vulnerable,” says Rudel.

To address gaps in chemical safety testing, the Silent Spring researchers identified a series of tests regulators could use to find chemicals that disrupt the pathways outlined in their new model. Chemicals that disrupt these pathways would be considered potential breast carcinogens, thereby discouraging their use in products.

“This study is an invaluable contribution to the field and a real wake-up call for regulators,” says Linda Birnbaum, former director of the National Institute for Environmental Health Sciences. “By holding on to an oversimplified model of how chemicals cause cancer, regulators have been missing critical information, potentially allowing toxic chemicals to enter our products, our air, and our water.”

The AOP project is part of Silent Spring Institute’s Safer Chemicals Program which is developing new cost-effective ways of screening chemicals for their effects on the breast. Knowledge generated by this effort will help government agencies regulate chemicals more effectively and assist companies in developing safer products.

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The look and feel of your neighborhood may affect your sleep

Those living in neighborhoods rated as having a stronger sense of safety tended to sleep longer, and that this rating appeared to be shaped by the streetscape.

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Your neighborhood’s “streetscape”—the physical environment of your street—is something that you have probably never consciously thought about, despite seeing it every day. But what if the streetscape was affecting you on a subconscious level and disrupting your sleep? 

This intriguing question is posed by the findings of a study led by Professor Daisuke Matsushita of the Graduate School of Human Life and Ecology at Osaka Metropolitan University. The research team used AI to analyze more than 200,000 Google Street View images to identify visual neighborhood characteristics. They then linked these characteristics to the self-reported sleep of 1,089 working adults living on the lower floors of apartments in Tokyo, who were most likely to be affected by the streetscape.  

They found that those living in neighborhoods rated as having a stronger sense of safety tended to sleep longer, and that this rating appeared to be shaped by the streetscape. Generally, people slept longer in areas with lots of greenery, such as leafy trees, on the street. Similarly, high “enclosure”—meaning many tall vertical buildings and few wide-open spaces—was also associated with longer sleep and fewer insomnia symptoms. 

However, the study also made a surprising finding. The researchers found that highly walkable streetscapes, such as those with more sidewalks and traffic signs, were associated with a lowered sense of safety and shortened sleep duration.  

This suggests that walkability does not always represent a reassuring environment. Instead, a possible explanation is that streets with extensive pedestrian infrastructure are often busier, more crowded, and used by more strangers, which may be perceived as less safe or less relaxing than quieter residential streets.  

“This study demonstrates the potential for evaluating streetscape characteristics across large geographic areas in a cost-effective manner,” Dr. Matsushita said. “Based on the technique used in this study, cities could potentially measure perceived safety, beauty, liveliness, and enclosure as well as pollution and noise.”  

“We hope that opening up this new perspective creates further possibilities for designing healthier neighborhoods,” he concludes.  

The findings were published in Building and Environment.

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Workout or nap? Either can help your sleepless brain, study finds

People who either completed 20 minutes of moderate-to-vigorous exercise or took a 90-minute nap performed about 22 per cent better on memory tests after 30 hours without sleep than those who did neither.

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A short workout or a nap can help protect memory after a sleepless night, a McGill University-led study has found.

Researchers found people who either completed 20 minutes of moderate-to-vigorous exercise or took a 90-minute nap performed about 22 per cent better on memory tests after 30 hours without sleep than those who did neither. The findings, published in Proceedings of the National Academy of Sciences (PNAS), point to practical ways to counter the effects of sleep deprivation.

“Sleep loss affects nearly every aspect of how we think and function, but many people can’t simply stop what they’re doing and get more sleep,” said senior author Marc Roig, Professor in McGill’s School of Physical and Occupational Therapy. “Our findings show that even a brief bout of exercise may help preserve one of our most important cognitive abilities.”

The study involved 54 healthy young adults who stayed awake for 30 consecutive hours under lab supervision. Participants were then assigned to one of three groups: a 20-minute cycling session, a 90-minute nap or a control condition. Three days later, researchers tested their memory for images they had viewed immediately after the intervention. Those who exercised or napped remembered significantly more images than participants who did neither.

Same result, different pathways

While the memory benefits were nearly identical, brain recordings revealed that exercise and napping helped in different ways.

Napping appeared to help the brain recharge, making it easier to take in and remember new information. Exercise, by contrast, helped the brain use its remaining resources more efficiently, without making participants feel more tired.

The findings could eventually inform fatigue-management strategies in workplaces where sleep loss is common and mistakes can have serious consequences, such as health care, transportation and emergency response.

“A nap isn’t always possible in the middle of a shift,” said first author Madhura Lotlikar, a doctoral candidate in McGill’s Department of Neurology and Neurosurgery. “Exercise is accessible, inexpensive and easy to implement. That makes it a promising tool to help people stay cognitively sharp when sleep is limited.”

The researchers emphasize that exercise cannot replace sleep, but it may help people function better when getting enough rest isn’t possible.

About the study

Protecting episodic memory after sleep loss: Similar benefits of exercise and naps via distinct neural contributions” by Madhura Lotlikar and Marc Roig et al., was published in Proceedings of the National Academy of Sciences of the United States of America.

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Study links coffee consumption to metabolic health and sex hormones

Despite having a similar body mass index (BMI), individuals with higher coffee consumption had lower total and visceral fat and greater skeletal muscle mass than those who consumed less coffee.

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Coffee is one of the world’s most widely consumed beverages, and previous research has linked its consumption to a lower risk of conditions such as type 2 diabetes and cardiovascular disease. However, the biological mechanisms behind these benefits remain unclear. A new Finnish study links habitual coffee consumption to healthier body composition and metabolic markers, while revealing distinct associations with sex hormones in men and women.

The study, conducted at the University of Oulu, analysed data from 2,264 participants aged 46 in the Northern Finland Birth Cohort 1966. Researchers examined how habitual coffee consumption was associated with circulating metabolites, cardiometabolic risk markers and sex hormones.

Despite having a similar body mass index (BMI), individuals with higher coffee consumption had lower total and visceral fat and greater skeletal muscle mass than those who consumed less coffee.

In both men and women, higher coffee consumption was correlated with lower circulating levels of branched-chain amino acids, biomarkers that have previously been linked to insulin resistance and an increased risk of type 2 diabetes when chronically elevated.

The strongest sex-specific associations were observed in men. Higher coffee consumption was linked to a more favourable glucose–insulin profile, higher concentrations of total and bioavailable testosterone, and increased levels of sex hormone-binding globulin (SHBG). At the same time, free testosterone and the free androgen index were modestly lower. In women, hormonal associations were more limited and were primarily characterised by higher SHBG and lower measures of free androgens.

“Coffee is consumed by millions of people every day, yet we still know surprisingly little about how it relates to our metabolism and hormones. What stood out in our findings was a distinct hormonal signature that didn’t disappear even after we took into account BMI and lifestyle factors, with several of these associations differing between men and women,” says Luca Verroest, lead author of the study and Doctoral Researcher at the University of Oulu.

The results suggest that hormonal pathways may partly explain the relationship between coffee consumption and metabolic health. However, as this was an observational study, the findings demonstrate associations rather than cause-and-effect relationships.

The study is particularly relevant in Finland, one of the world’s highest coffee-consuming countries, where annual consumption averages around 11.8 kilograms per person.

The researchers say the findings provide a foundation for future studies aimed at determining whether coffee itself drives these biological changes and identifying the compounds responsible. These questions are currently being investigated in animal models, with the long-term goal of progressing to human intervention studies. Further research will be needed before the findings could inform dietary recommendations.

The study, Associations of habitual coffee intake with testosterone and cardiometabolic markers: the Northern Finland Birth Cohort 1966 study, has been published in the European Journal of Nutrition.

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