Report links recommended physical activity levels to lower risk of seven cancers

by American Cancer Society

Credit: CC0 Public Domain

A pooled analysis of nine prospective studies involving more than 750,000 adults finds that recommended amounts of leisure-time physical activity were linked to a lower risk for seven cancers, with several cancer types having a 'dose/response' relationship. The study was led by investigators at the National Cancer Institute, the American Cancer Society, and the Harvard T.H. Chan School of Public Health and appears in the Journal of Clinical Oncology.

06 jan 2020--While it's long been known that physical activity is associated with a lower risk of several cancers, less clear has been the shape of the relationship and whether recommended amounts of physical activity are associated with lower risk. Updated guidelines for activity now state that people should aim for 2.5 to 5 hours/week of moderate-intensity activity or 1.25 to 2.5 hours/week of vigorous activity. Moderate-intensity activities are those that get you moving fast enough or strenuously enough to burn off three to six times as much energy per minute as sitting quietly (3 to 6 METs). Vigorous-intensity activities burn more than 6 METs.

For the current analysis, investigators pooled data from nine prospective cohorts with self-reported leisure-time physical activity and follow-up for cancer incidence, looking at the relationship between physical activity with incidence of 15 types of cancer.

They found engaging in recommended amounts of activity (7.5 to 15 MET hours/week) was associated with a statistically significant lower risk of seven of the 15 cancer types studied, with the reduction increasing with more MET hours. Physical activity was associated with a lower risk of colon cancer in men (8% for 7.5 MET hours/week; 14% for 15 MET hours/week), female breast cancer (6%-10%), endometrial cancer (10%-18%), kidney cancer (11%-17%), myeloma (14%-19%), liver cancer (18%-27%), and non-Hodgkin lymphoma (11%-18% in women). The dose response was linear in shape for half of the associations and nonlinear for the others.

The analysis had some limitations: Even with 750,000 participants, patient numbers were limited for some cancers; participants were primarily white; there was a limited number of cohorts with detailed physical activity measures; and the authors relied on self-reported physical activity.

The authors conclude: "These findings provide direct quantitative support for the levels of activity recommended for cancer prevention and provide actionable evidence for ongoing and future cancer prevention efforts."

"Physical activity guidelines have largely been based on their impact on chronic diseases like cardiovascular disease and diabetes," said Alpa Patel, Ph.D., senior scientific director of epidemiology research at the American Cancer Society. "These data provide strong support that these recommended levels are important to cancer prevention, as well."

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More information: Amount and Intensity of Leisure-Time Physical Activity and Lower Cancer Risk, Matthews et al. Journal of Clinical Oncology (2019). DOI: 10.1200/JCO.19.02407

Journal information: Journal of Clinical Oncology 

Provided by American Cancer Society 

Drug dramatically reduces risk of dangerous blood clots in cancer patients

Blood clots in the legs can cause swelling, redness and pain. If a clot forms in the lungs, it can be deadly. New research provides the first approach for safely preventing these clots in people with cancer. Credit: The Ottawa Hospital

A Canadian clinical trial published in the New England Journal of Medicine provides the first approach for safely preventing blood clots (or venous thromboembolism) in people with cancer. About half of people newly diagnosed with a solid cancer could be candidates for the strategy, which involves a low dose of a direct oral anticoagulant called apixaban.

05 dec 2018--"Cancer increases the risk of blood clots, which in turn can cause pain, reduce quality of life and increase the risk of death," said senior author Dr. Philip Wells, a hematologist, senior scientist and Chief of Medicine at The Ottawa Hospital and the University of Ottawa. "Our study shows for the first time that we can safely prevent these clots in many people with cancer."
A key part of the study was the identification of cancer patients with a higher risk of developing blood clots. This was done using the Khorana score, which is based on blood tests results and other clinical factors. The researchers found that about half of all people starting cancer chemotherapy were in the higher risk group. They enrolled 563 of these patients from 13 Canadian centres in the trial and randomly assigned them to receive apixaban (2.5 mg twice a day for six months) or a placebo.
Of the 275 patients in the placebo group, 28 suffered a blood clot within six months (10.2 percent) compared to 12 of 288 in the apixaban group (4.2 percent). The researchers also looked at side effects related to bleeding, as these are known to increase with the use of anticoagulants. Three patients in the placebo group suffered a major bleed (1 percent) compared to six patients in the apixaban group (2.1 percent), but all bleeds were treatable.
"Anticoagulants are commonly used to prevent blood clots in other high-risk groups, but the traditional thinking has been that these drugs would cause too much bleeding in people with cancer," said first author Dr. Marc Carrier, a hematologist, senior scientist and associate professor at The Ottawa Hospital and the University of Ottawa. "Our study shows that if you select the right patients and use a relatively low dose of a direct oral anticoagulant, the benefits easily outweigh the risks."
With about 1.9 million people diagnosed with cancer every year in Canada and the U.S., the researchers estimate that about half, or 950,000 could be considered for the blood clot prevention strategy tested in the study. In this population, the strategy would be expected to prevent clots in six percent, or 57,000 people. The preventative strategy would also save money, as treating blood clots can be very expensive.
This research means a lot to Harold Black, 76, who developed a cancer-associated blood clot in his lungs (pulmonary embolism) in September 2018. The large clot required two days of treatment and monitoring at The Ottawa Hospital, followed by ongoing daily heparin injections in the belly.
"I feel very lucky because I was told that the first sign of a pulmonary embolism is often death," said Black. "If this research prevents people like me from developing blood clots, that will make a big difference for a lot of people."
The blood clot (thrombosis) program at The Ottawa Hospital and the University of Ottawa is the largest and the most research-intensive in the world. With four publications in the New England Journal of Medicine since 2015, their research is transforming lives both in Ottawa and around the world.
"I want to thank the outstanding physicians, nurses, research coordinators and other members of our thrombosis team," said Dr. Wells. "But above all, I want to thank our patients for participating in our research and helping us improve care for them and others around the world."
This study was sponsored by the Ottawa Hospital Research Institute, with funding primarily from the Canadian Institutes of Health Research. The BMS-Pfizer Alliance also provided funding but had no role in designing the study or analyzing the results. The study was also supported by the CanVECTOR research network and the Ottawa Methods Centre. Research at The Ottawa Hospital is possible because of generous donations to The Ottawa Hospital Foundation.

More information: Marc Carrier et al, Apixaban to Prevent Venous Thromboembolism in Patients with Cancer, New England Journal of Medicine (2018). DOI: 10.1056/NEJMoa1814468


Provided by The Ottawa Hospital

Biochemists follow clues toward Alzheimer's, cancer, longevity

In microscopic images of muscle tissue from normal fruit flies (left), fluorescent tags reveal uniform levels of the structural protein actin (blue) and almost no poly-UB, a protein aggregate that is broken apart and recycled by healthy cells. In muscle tissue from flies lacking HSP gene activity (right), actin levels are reduced and cells contain a toxic buildup of poly-UB. Credit: James McNew/Rice University

James McNew's and Michael Stern's biochemical hunt for the root cause of a rare, paralyzing genetic disorder is a 10-year quest that's taken an unexpected turn toward everyday killers such as Alzheimer's disease, cancer and aging.

05 aug 2018--The National Institutes of Health has awarded the Rice University scientists a five-year R01 grant to investigate a biochemical domino effect that begins with a critical regulatory protein called TOR and ends with cells dying of oxidative stress. TOR regulates cell growth and survival and only recently became a focus for Stern and McNew, professors of biochemistry and cell biology in Rice's Department of BioSciences and co-investigators on the $1.9 million grant from the NIH's National Institute of Neurological Disorders and Stroke.
"It's known that TOR controls starvation in virtually every animal, including humans," McNew said. "Decreased TOR activity has even been found to increase the life span of yeast, worms and fruit flies, and some studies have found that TOR-inhibiting drugs increase the life span of mice. Increased TOR activity is also involved in cancer and has been implicated in Alzheimer's, Parkinson's and other neurodegenerative diseases, including one called hereditary spastic paraplegia (HSP) that we have studied for many years."
HSP, a rare disorder that affects about 20,000 people in the U.S., is marked by numbness and weakness in the legs and feet due to progressive deterioration of the longest cells in the body—the neurons that connect the spine to the lower legs.
In 2016 Stern, McNew and colleagues used hundreds of experiments on dozens of mutant strains of fruit flies to show how an HSP gene produced defective synapses at the junctions between nerve and muscle cells. In follow-up work last year, McNew, Stern and postdoctoral researcher Shiyu Xu conducted more experiments to see exactly how these synapse defects caused neurons to malfunction and die.
"Shiyu wasn't able to find any evidence of neurodegeneration, but he did find evidence of muscle degeneration," Stern said. "That was a surprise, and we didn't know what to make of it at first. Even though nerve damage is a known cause of muscle atrophy, conventional wisdom is that the nerve cells die first."
Intrigued, the group conducted experiments to see what was happening at the molecular level. Tests suggested elevated TOR activity in the degenerating muscle cells. TOR is short for "target of rapamycin"; when TOR was discovered in the early 1990s, researchers only knew it was the target of a natural compound called rapamycin, an immunosuppressant that had been widely prescribed for decades to transplant recipients.
"We were convinced it was TOR after Shiyu showed he could slow down the muscle degeneration by giving the flies rapamycin," Stern said.

At a healthy synapse (top), neuron-muscle communication (thick green arrow) prevents TOR activation in muscle, permitting repair of cellular structures and muscle survival. Synapse defects (bottom) from HSP mutations and other neuronal disorders disrupt this communication (thin green arrow), which activates TOR protein in the muscle, allowing junk proteins to build up and cause muscle degeneration and ultimately death. Credit: James McNew/Rice University

TOR is an important master regulator of growth and nutrient-sensing. When fully activated, TOR promotes growth so aggressively that cells forgo daily chores such as repairing structural damage and recycling partially functional organelles. In times of extreme stress or starvation, TOR is fully deactivated so the cell can enter a survival mode and conserve scarce resources.
"TOR isn't an on-off switch as much as a knob for dialing growth up or down," McNew said. "It's not that high TOR is bad and low TOR is good. Each is needed under certain conditions, and TOR's function—which is essential in all higher-order life, from yeast to humans—is to modulate growth to match the conditions it's detecting."
Stern said, "What appears to be happening in the muscle cells that aren't receiving neuronal signals is that the knob gets switched onto high and stays there. TOR locks the cells into this aggressive, pro-growth mode and they stop cleaning up all of the reactive oxygen species, or free radicals, which gradually build up and cause such high levels of stress that the cell dies."
Stern said this hypothesis jibes with observations from numerous other studies that have found high TOR levels and high levels of oxidative stress in the brain cells of patients with Alzheimer's as well as the atrophied muscles of patients who are paralyzed or bedridden.
"In muscle atrophy studies in mice, where the motor neuron is cut, they've found that TOR is activated," he said. "This might be mechanistically similar to our case or to what's been seen in Alzheimer's because people have also found activation of the stress pathway that's induced by reactive oxygen species."
Stern said previous studies also have identified some of the molecular players involved in the degeneration domino effect—including two proteins known as the JNK kinase and the FOXO transcription factor—but he and McNew are the first to connect the dots between TOR and the stress-pathway proteins.
"We also see FOXO activation in our degeneration model, but we know—or at least we think we know—what is activating FOXO," Stern said. "We hypothesize that TOR causes a buildup of reactive oxygen species that in turn activates a molecule called JNK, which activates FOXO."
McNew said focusing on the damage from overactive TOR means that any clues he and Stern find could potentially apply to any disease or condition in which TOR activation is implicated.
"The things that cause TOR to get turned on in a neuron are probably very different than those that turn it on in a liver cell or a white blood cell," he said. "We're focused on the downstream part because once you get TOR turned on, we think it does a handful of things we understand and can directly test. And those are likely to be uniform across different cell types and different conditions. That means anything we find could inform not only HSP pathology but also cancer and neurodegenerative diseases like Alzheimer's and Parkinson's."


Provided by Rice University

Science Says: What we know about cancer risk and coffee

Trouble is brewing for coffee lovers in California, where a judge ruled that sellers must post scary warnings about cancer risks. But how frightened should we be of a daily cup of joe? Not very, some scientists and available evidence seem to suggest.

02 april 2018--Scientific concerns about coffee have eased in recent years, and many studies even suggest it can help health.
"At the minimum, coffee is neutral. If anything, there is fairly good evidence of the benefit of coffee on cancer," said Dr. Edward Giovannucci, a nutrition expert at the Harvard School of Public Health.
The World Health Organization's cancer agency moved coffee off the "possible carcinogen" list two years ago, though it says evidence is insufficient to rule out any possible role.
The current flap isn't about coffee itself, but a chemical called acrylamide (ah-KRILL-ah-mide) that's made when the beans are roasted. Government agencies call it a probable or likely carcinogen, based on animal research, and a group sued to require coffee sellers to warn of that under a California law passed by voters in 1986.
The problem: No one knows what levels are safe or risky for people. The U.S. Environmental Protection Agency sets acrylamide limits for drinking water, but there aren't any for food.
"A cup of coffee a day, exposure probably is not that high," and probably should not change your habit, said Dr. Bruce Y. Lee of Johns Hopkins Bloomberg School of Public Health. "If you drink a lot of cups a day, this is one of the reasons you might consider cutting that down."
Here's what's known about the risks.
THE CHEMICAL
Start with the biggest known risk factor for cancer—smoking—which generates acrylamide . In the diet, French fries, potato chips, crackers, cookies, cereal and other high-carbohydrate foods contain it as a byproduct of roasting, baking, toasting or frying.
Food and Drug Administration tests of acrylamide levels found they ranged from 175 to 351 parts per billion (a measure of concentration for a contaminant) for six brands of coffee tested; the highest was for one type of decaf coffee crystals. By comparison, French fries at one fast food chain ranged from 117 to 313 parts per billion, depending on the location tested. Some commercial fries had more than 1,000.
Even some baby foods contain acrylamide, such as teething biscuits and crackers. One brand of organic sweet potatoes tested as having 121 parts per billion.
WHAT'S THE RISK?
The "probable" or "likely" carcinogen label is based on studies of animals given high levels of acrylamide in drinking water. But people and rodents absorb the chemical at different rates and metabolize it differently, so its relevance to human health is unknown.
A group of 23 scientists convened by the WHO's cancer agency in 2016 looked at coffee—not acrylamide directly—and decided coffee was unlikely to cause breast, prostate or pancreatic cancer, and that it seemed to lower the risks for liver and uterine cancers. Evidence was inadequate to determine its effect on dozens of other cancer types.
THE CALIFORNIA LAW
Since 1986, businesses have been required to post warnings about chemicals known to cause cancer or other health risks—more than 900 substances are on the state's list today—but what's a "significant" risk is arguable.
Coffee sellers and other defendants in the lawsuit that spurred Thursday's ruling have a couple weeks to challenge it or appeal.
The law "has potential to do much more harm than good to public health," by confusing people into thinking risks from something like coffee are similar to those from smoking, Giovannucci said.
The International Food Information Council and Foundation, an organization funded mostly by the food and beverage industry, says the law is confusing the public because it doesn't note levels of risk, and adds that U.S. dietary guidelines say up to five cups of coffee a day can be part of a healthy diet.
Dr. Otis Brawley, the American Cancer Society's chief medical officer, said, "The issue here is dose, and the amount of acrylamide that would be included in coffee, which is really very small, compared to the amount from smoking tobacco. I don't think we should be worried about a cup of coffee."
Amy Trenton-Dietz, public health specialist at the University of Wisconsin-Madison, said the California ruling contrasts with what science shows.
"Studies in humans suggest that if anything, coffee is protective for some types of cancer," she said. "As long as people are not putting a lot of sugar or sweeteners in, coffee, tea and water are the best things for people to be drinking."

More than 2,500 cancer cases a week could be avoided

Preventable cancer risk factors. Credit: Cancer Research UK

More than 135,500 cases of cancer a year in the UK could be prevented through lifestyle changes, according to new figures from a Cancer Research UK landmark study published today.

24 mar 2018--This equates to 37.7% of all cancers diagnosed each year in the UK - rising to 41.5% in Scotland.
The latest figures, calculated from 2015 cancer data, found that smoking remains the biggest preventable cause of cancer despite the continued decline in smoking rates.
Tobacco smoke caused around 32,200 cases of cancer in men (17.7% of all male cancer cases) and around 22,000 (12.4%) in women in 2015, according to the research published in the British Journal of Cancer.
Excess weight is the second biggest preventable cause of cancer. Around 22,800 (6.3%) cases of cancer a year are down to being overweight or obese. This amounts to around 13,200 (7.5%) cases of cancer in women and around 9,600 (5.2%) in men.
Obesity causes 13 types of cancer, including bowel, breast, womb and kidney. And the results suggest that more than 1 in 20 cancer cases could be prevented by maintaining a healthy weight.
The third biggest preventable cause of cancer is overexposure to UV radiation from the sun and sunbeds, which causes around 13,600 cases of melanoma skin cancer a year (3.8% of all cancer cases).
Other preventable causes of cancer include drinking alcohol, eating too little fibre (causing around 11,900 and around 11,700 cases respectively, which is 3.3% each) and outdoor air pollution. While air pollution is to blame for around 3,600 lung cancer cases a year (1% of all cancer cases), it still causes far fewer cases of lung cancer than tobacco.
Sir Harpal Kumar, Cancer Research UK's chief executive, said: "Leading a healthy life doesn't guarantee that a person won't get cancer, but it can stack the odds in your favour. These figures show that we each can take positive steps to help reduce our individual risk of the disease. "This research clearly demonstrates the impact of smoking and obesity on cancer risk. Prevention is the most cost-effective way of beating cancer and the UK Government could do much more to help people by making a healthy choice the easy choice."
Professor Linda Bauld, Cancer Research UK's prevention expert, said: "These new figures show that the battle to conquer smoking-related cancer is far from over. But the declining numbers of smokers show that prevention strategies are working.
"Obesity is a huge health threat right now, and it will only get worse if nothing is done. The UK Government must build on the successes of smoking prevention to reduce the number of weight-related cancers. Banning junk food TV adverts before the 9pm watershed is an important part of the comprehensive approach needed."
Janet Boak, 55, a grandmother of three from Carlisle, was diagnosed with womb cancer at 51 after she noticed spots of blood four years after her menopause. During surgery to remove two fibroids from her womb, cancer was found. Janet then had a full hysterectomy to remove her womb and cervix. Because the cancer was caught in the earliest stages and hadn't spread, she avoided any further treatment.
Volunteering to take part in some womb cancer research after her treatment, Janet was shocked to find out that the possible contributing factors for womb cancer included being obese and being inactive.
Janet said: "That was me. At almost 20st and wearing up to a size 30, I was huge and most of my weight was around my stomach. I couldn't remember the last time I did any exercise.
"Of course I'd known I needed to lose weight but I hadn't realised just how much I was putting my life at risk." Janet joined a local slimming group in 2015, changed her diet and started taking exercise.
She said: "The weight gradually fell off and now, over two years on, I've lost more than 6st and wear a size 16. I could barely keep up with my three young grandchildren before but now I'm always running around after them. I even ran Race for Life for Cancer Research UK last year - something I never imagined I would do.
"Getting cancer was terrifying but it was the wake-up call I needed. I don't know what the future holds but at least I know I'm doing all I can to stay healthy and happy."

More information: British Journal of Cancer (2018). DOI: 10.1038/s41416-018-0029-6


Provided by Cancer Research UK

Overdiagnosis—when finding cancer can do more harm than good

Not all cancers are equal.

11 mar 2018--Some grow fast and spread quickly, while others grow so slowly (or even not at all) that if they went undetected they wouldn't cause any problems. Even if left untreated, a person wouldn't be harmed by their cancer.
When these harmless cancers are found they're said to be 'overdiagnosed'. This happens more often with certain types of cancer, and is usually tied to particular types of cancer screening that test people without symptoms, such as breast screening.
The problem is that when these types of cancer are diagnosed early it's impossible to tell the potentially harmful ones from the harmless ones. Everyone is then usually offered treatment. And this means that some will be exposed to the potential side effects of treatment, and worry of a cancer diagnosis, when they didn't need to be. This is called overtreatment.
Overdiagnosis is one of the key things to consider when working out the balance of possible benefits and harms of cancer screening. Keep in mind, overdiagnosed cancers aren't the same as when a test finds something abnormal that turns out not to be cancer (so-called false positive test results), another risk of screening and many other types of test. An overdiagnosed cancer is a true cancer, but it's one that wouldn't have caused harm in that person's lifetime.
So the challenge then becomes shifting our thinking of cancer as always needing urgent treatment to a disease that sometimes we can live with, or be unaware of and unaffected by.
Over the last few decades overdiagnosis has been receiving more attention. And with new cancer detection technology on the horizon, ranging from blood tests to wristbands, it's important that we learn more about it and work out how to minimise it.

What's the evidence?

Some of the earliest evidence around overdiagnosis came from autopsy studies. Experts found undiagnosed cancers in people who had died from a cause other than cancer. This showed in some cases people can live out their life without ever knowing a cancer is there, or being harmed by it.
Professor Gilbert Welch, from the Dartmouth Institute for Health Policy and Clinical Practice in the US, is a pioneer in raising awareness of the challenge of overdiagnosis. And he says that overdiagnosis isn't something that doctors or researchers usually directly observe. "The occasional exception is when we do nothing for a diagnosed cancer and the patient goes on to die of something else," he says.
Other evidence for the phenomenon has come from digging into cancer statistics, particularly when comparing the number of people diagnosed with a cancer (incidence) with those that die from it (mortality).
"The easiest evidence to understand is when incidence shoots up following early diagnosis and mortality stays the same," says Welch. "Here South Korea serves as the poster child."

Thyroid cancer in South Korea – a true epidemic?

South Korea introduced free screening programmes for a range of cancers in 1999, with thyroid cancer screening also available for a small fee. A decade later, the incidence of thyroid cancer in South Korea had increased dramatically.

If the number of cases of thyroid cancer were really increasing, and if we assume they're all cancers that needed to be found and treated, we'd also expect an increase in the number of people dying from thyroid cancer.
That didn't happen.
There are two possible explanations for this:

1. Thyroid cancer treatment improved dramatically at the same time as more people were being diagnosed, so lots more people were surviving the disease.
2. The cancers that were being picked up through screening were overdiagnosed.

The second explanation is far more likely. In other words, simply scanning more thyroids picked up more of the slow-growing, harmless cancers that didn't need to be found and treated in the first place.
Importantly, overdiagnosis can mean cancer survival statistics don't always accurately represent the progress we're making. For example, if more harmless cancers are found and treated, many more people will survive the disease they've been diagnosed with. So it can be tricky to untangle the true impact of things like better treatments.
But some cancers are much more prone to overdiagnosis than others, such as breast and prostate cancers.

Breast screening: saving lives and balancing harms

Breast screening picks up early stage cancers that are more likely to be treated successfully. But it also comes with potential harms, including overdiagnosis, because many of those early invasive breast cancers wouldn't have gone on to cause trouble. Women need this information so they can make a fully informed decision about whether or not to go for screening.
Research has shown that for each woman whose life is saved through breast cancer screening, around three will be diagnosed with a breast cancer that would have never caused harm or death.
A cancer diagnosis causes distress. And because breast screening and diagnostic tests can't yet tell the dangerous cancers that need treating from the harmless ones that don't, some people will experience that distress unnecessarily. So to be on the safe side, treatment will be recommended to all patients, which can also lead to unnecessary side effects.
"For every woman who is prevented from dying from breast cancer, three others will be diagnosed that wouldn't have otherwise if they didn't participate in breast screening," explains Professor Peter Sasieni, Cancer Research UK's expert in cancer screening and epidemiology from King's College London.
"Those three will be treated and will probably have surgery, radiotherapy and possibly hormonal therapy."
"I think the language we use to talk about cancer is a big problem in society," he adds. "I think most people still think of a cancer diagnosis as a death sentence."

"The Holy Grail is finding something that tells us which cancers are harmless and which aren't, and then we can distinguish between them and ignore the harmless ones."
Screening can save lives by diagnosing cancer at an earlier stage and, in some cases, preventing it from developing in the first place. But the decision to introduce new screening programmes has to be carefully thought through.

Prostate cancer: why there's no UK screening programme

Prostate specific antigen (PSA) is a molecule made by the prostate and detected in blood samples. A man's PSA level can be raised for many reasons, including an enlarged prostate, infection and prostate cancer.
Clinical guidelines recommend PSA testing in men with prostate cancer to monitor if their disease gets worse. And men with low-risk prostate cancer that hasn't spread can be monitored with regular PSA testing as an alternative to surgery or radiotherapy.
But there are longstanding debates around if the PSA test should be used for screening to look for prostate cancer in men with no symptoms.
There's no national prostate cancer screening programme in the UK, because the PSA test isn't reliable enough. A large study from 2013 looked at the results of different trials comparing men who had prostate screening and those who didn't. The study showed that screening didn't save any lives, and the men who took part in screening were more likely to be overdiagnosed.
The latest findings from a major Cancer Research UK-funded PSA trial included over 400,000 men and has backed up that a one-off PSA test doesn't save lives.

Seek and you shall find

No screening test is perfect and there's always a trade-off between lives saved and the harms of overdiagnosis and overtreatment. It's up to researchers to improve tests and tip the balance.
We're in exciting times when it comes to the potential for technology and innovation to diagnose cancer earlier. We need to be able to find and diagnose cancers early because when cancer is found at an earlier stage it's easier to treat.
But the flip side is that new tests and more sensitive tech can come with a higher risk of picking up cancers that would never have gone on to cause harm. So it's vital that researchers consider not only how to find cancer earlier, but also how to reduce overdiagnosis and ensure we're picking up the cancers that need treating.
Lung cancer screening is an example of where this can happen.
Most lung cancers are diagnosed at a late stage (stage 4), and this is largely to blame for lung cancer survival being so poor. Diagnosing more cancers early (stage 1 and 2) is crucial to save lives. And screening might be a way of doing this.

The US National Lung Screening Trial compared chest x-rays with low dose CT scans to pick up lung cancers. In other words, whether CT as a more advanced imaging technology has greater potential than standard chest x-rays to diagnose lung cancer in people without symptoms and stop people dying from the disease.
The researchers looked at over 53,000 people aged between 55 and 74 at high risk of lung cancer based on their smoking history. Half were screened with chest x-rays and the others had CT scans.
The group that had CT scans were 20% less likely to die of lung cancer than those who had chest x-rays, suggesting CTs can save more lives. But compared with the x-ray group, the risk of having a lung cancer overdiagnosed in the CT group was around 18%. That's nearly 1 in 5 people who were diagnosed with a lung cancer that wouldn't have gone on to cause any harm at all in their lifetime. Researchers working on lung screening know this is something to be addressed as they test what might balance the harms and benefits of lung screening.
"It's important to emphasize that harms of overdiagnosis can coexist with the benefit of a mortality reduction – they aren't mutually exclusive," says Welch.
There isn't a national lung cancer screening programme in the UK because it's not clear if the potential benefits would outweigh the potential harms. The largest European trial investigating lung cancer screening is still underway. The latest results, expected out in the next year, will hopefully shed more light on these issues.

What next?

Screening can help spot cancer early and save lives.
And the UK's national screening programmes exist because research has shown that the benefits outweigh the harms for the population at large.
But for an individual person, the decision to be screened or not should be an informed choice.
"Currently, in order to have the benefits of screening, there has to be some overdiagnosis," says Sasieni.
If you're unsure about what to do if you get an invitation for screening, visit our website or speak to your doctor.
Research into better tests and improved technology will help pick up cancers earlier.
The challenge then is finding out how to tell the dangerous cancers from the harmless ones. But with overdiagnosis moving further in to the spotlight, and with our strong commitment to diagnosing cancers earlier, researchers are better placed than ever to tackle this.


Provided by Cancer Research UK

Senescence promotes chemotherapy side effects and cancer relapse

Credit: Buck Institute

Standard chemotherapy is a blunt force instrument against cancer – and it's a rare cancer patient who escapes debilitating side effects from systemic treatments that mostly affect dividing cells, both malignant and healthy, throughout the body.

21 jan 2017--Researchers at the Buck Institute and elsewhere now show that chemotherapy triggers a pro-inflammatory stress response termed cellular senescence, promoting the adverse effects of chemotherapy as well as cancer relapse and metastasis. Eliminating the senescent cells in mice prevented the side effects and relapse. The research is published in Cancer Discovery.
"While chemotherapy does save lives, it often comes with a very high price," said Judith Campisi, PhD, Buck faculty and senior scientist on the study. "Our work in mice studied the effects of chemotherapy on cancer relapse and other serious side effects. It provides a proof-of-principle that we hope can be translated into clinical practice."
Campisi's latest work highlights the two-faced nature of cellular senescence. It's a biological mechanism that puts a break on cancer by permanently stopping stressed cells from dividing, but it also contributes to aging and late-life cancers. That's because senescent cells are not benign – they secrete inflammatory molecules that damage neighboring tissues and cells. "Chemotherapy induces widespread senescence, contributing to persistent local and systemic inflammation," Campisi said. "That's why many patients feel so awful following treatment."
The research, led by Marco Demaria, PhD, a former postdoc in the Campisi lab, utilized transgenic mice that permit tracking and eliminating senescent cells. Results showed that eliminating chemotherapy-induced senescent cells reduced several short-and long-term effects of treatment, including bone marrow suppression, toxicity to the heart, cancer recurrence and metastasis, and physical activity and strength. Common chemotherapy drugs Doxorubicin, Paclitaxel, Temozolomide and Cisplatin were used to treat the mice.
Demaria, who is now a principle investigator at the European Research Institute for the Biology of Ageing, at the University Medical Center, Groningen, Netherlands, said some of the most striking results involved running speed – an indicator of fatigue in mice. "Eliminating senescent cells was sufficient to almost entirely rescue the decline in physical activity in the treated mice," he said. "Normally, mice spend 40 percent of their time running. After chemotherapy that activity dropped to 10 percent. When we knocked out the senescent cells the mice returned to normal running."
"Fatigue, which can be long-lasting, is a big deal for patients on chemotherapy," said Norman E. Sharpless, MD, Director of the Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill and a co-author of the study, "Years later they often say that was the worst part of the treatment.
"Chemotherapy-induced bone marrow injury can lead to reduction in blood cell production, which can contribute to chemotherapy-induced fatigue," Said Daohong Zhou, MD, Associate Director for Basic Research of the Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences in Little Rock and a co-author of the study, "Eliminating senescent cells can promote bone marrow recovery after chemotherapy."
Sharpless looked at blood markers of cellular senescence in 89 women with breast cancer before they underwent chemotherapy aimed at curing their disease. "Women who went into chemotherapy with the highest existing burden of senescent cells experienced the most debilitating fatigue after treatment," he said. "It didn't really matter what particular drug was used – the results following chemotherapy tracked to the existing burden of senescent cells."
"We are excited about the potential applications of this work," said Campisi. "It would be a huge benefit if we could reduce the risk of cancer relapse and metastasis in patients. We also think it would be great to mitigate the other side effects of chemotherapy, the fear of which sometimes keep patients from seeking treatment."

More information: M. Demaria et al. Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse, Cancer Discovery (2016). DOI: 10.1158/2159-8290.CD-16-0241


Provided by Buck Institute

New research reveals cancers need a 'perfect storm' of conditions to develop

Graphical definition of stem cells. Credit: Cancer Research UK

Scientists have demonstrated for the first time the 'perfect storm' of conditions that cells need to start forming cancer, helping to explain why some organs are more susceptible to developing the disease, according to a new study published in Cell today.

26 aug 2016--The research, carried out by scientists at Cancer Research UK's Cambridge Institute at the University of Cambridge and St Jude's Children's Research Hospital in the United States, shows that cancers are more likely to start in stem cells - special cells that copy themselves so the body can grow new cells, repair damaged tissue and replace old cells.
But while these stem cells are more susceptible to developing into cancer, they also need to have accumulated DNA mistakes and be replicating to repair damage or wear and tear for cancers to start.
These DNA mistakes can happen randomly as stem cells replicate and they tend to build up with age, which is why cancer gets more common as we get older. They can also be caused by things in our environment such as tobacco smoke or UV radiation.
To find out how cancers start in different organs the researchers tagged one particular group of cells in mice with a fluorescent dye to track their behaviour. They then introduced DNA mistakes linked to different types of cancers into these cells.
Importantly, they found that DNA mistakes by themselves were not enough to cause cancer. In organs where DNA mistakes were introduced into dormant stem cells, there were no signs of cancer.

New research has demonstrated how cancers can start in stem cells. Credit: Cancer Research UK

Yet, in other organs that are exposed to lots of wear and tear - like the bowel - introducing DNA mistakes into the replicating stem cells caused cancer to start.
Professor Richard Gilbertson, lead researcher based at Cancer Research UK's Cambridge Institute at the University of Cambridge, said: "We can now say that cancer most likely starts in stem cells but is not just down to 'bad luck'. The development of cancer involves a 'perfect storm' of stem cells containing DNA mistakes that are replicating in response to damage or wear and tear.
"Although stem cells can sometimes go wrong by chance, our research shows that things in our environment that lead to more DNA mistakes or that damage organs, causing these stem cells to divide, increases the chances of the 'perfect storm' brewing. That's why behaviours like smoking or UV exposure raise the risk of developing cancer.
"Our work also shows why some types of cancer are more common than others, with tumours more likely to develop in organs with lots of replicating stem cells, for example the bowel."
"We hope finding out more about the way in which cancer develops will help us, and other scientists around the world, develop new ways to prevent and treat cancer."
Professor Karen Vousden, Cancer Research UK's chief scientist, said: "The study looks at the perplexing question of why we get cancer more often in some organs than others. This risk seems to be dictated by a combination of mutations in cancer-causing genes in stem cells, stem cell proliferation and tissue damage - which vary between different organs."

More information: Cell, DOI: 10.1016/j.cell.2016.07.045


Provided by Cancer Research UK

Exercise offers cancer survivors significant improvements in quality of life

For many cancer survivors, a better quality of life is as close as the nearest pair of sneakers. That's because a growing body of research, including two recent studies led by Yale Cancer Center, show that exercise is a powerful way for survivors to improve quality of life.

31 may 2015--The studies were presented at the 2015 Annual Meeting of the American Society of Clinical Oncology in Chicago. The first evaluated the effect of the LIVESTRONG at the YMCA program on cancer survivors who participated in twice-weekly, 90 minute exercise sessions for 3 months at local YMCAs. The other study explored whether home-based exercise programs that encouraged brisk walking could improve fatigue and quality of life for ovarian cancer survivors. Both studies showed exercise to be a potent tool for survivors to improve life in many areas.

The LIVESTRONG at the YMCA study was conducted by Dr. Melinda Irwin, associate professor of Epidemiology in Yale School of Public Health and associate director of population sciences at Yale Cancer Center; and Dr. Jennifer Ligibel of Dana Farber Cancer Institute. It evaluated 186 participants for quality of life, physical activity and fitness. After 12 weeks, participants were shown to experience significant increases in physical activity (71 percent exercising a minimum of 150 minutes/week vs. 26 percent for the control group); and improvements in both overall quality of life and fitness performance (according to a six- minute walk test). The participants had been diagnosed with stages I-IV of cancer and 50 percent had breast cancer. In addition, at the outset of the program, the majority of the participants had been inactive.

"For many people, quality of life is compromised after a cancer diagnosis. This study showed that exercise can improve patients' lives in a myriad of ways, regardless of how active they were in the past," said Irwin, first author on the study. "In addition to quality of life, physical activity is associated with risk of dying from cancer. The LIVESTRONG at the YMCA program could be a national model to increase exercise in cancer patients across the country."

The WALC study, conducted at Yale and led by Dr. Irwin, is the largest exercise trial of ovarian cancer survivors, It enrolled 144 ovarian cancer survivors who were not physically active and randomized them to an exercise group or control group. Each group received a weekly call from a counselor to discuss a health topic relevant to ovarian cancer survivors. For the exercise group, women also received physical activity counseling from a certified cancer exercise trainer during the calls.

The results showed that a moderate-intensity walking program can improve ovarian cancer survivors' quality of life, in particular physical functioning, improvement in pain and reduced fatigue. Women were interested in exercising and able to do so at recommended levels even though 55% had stage III or IV disease and 25% experienced a recurrence during the trial.

"Our hope is that this study will encourage survivors of even late-stage cancers to consider exercise as a way of coping with a number of issues that come with a cancer diagnosis," said Dr. Yang Zhou, first author on the study. "We also hope oncologists will use this study and others like it to refer patients to survivorship programs that incorporate exercise."

More information: "Randomized trial of exercise on quality of life and fatigue in women diagnosed with ovarian cancer: The Women's Activity and Lifestyle Study in Connecticut (WALC)." J Clin Oncol 33, 2015.abstracts.asco.org/156/AbstView_156_146487.html

Provided by Yale University

Cancer diagnoses will rise as population ages

Cancer is a leading cause of death in Virginia and researchers at the University of Virginia's Weldon Cooper Center for Public Service project that the rate of growth in new cancer cases will far outpace the growth of the population in the next 25 years, due to the overall aging of the population.

24 april 2015--The greatest number of new cancer diagnoses is projected in the major metropolitan areas, where most Virginians live. But rural localities with a larger share of older residents will experience the highest local cancer burden by having a higher proportion of their populations diagnosed with cancer over the next three decades.

This finding and others related to cancer projections across Virginia are detailed in a Census Brief released today, the sixth in a series of short publications depicting trends in census and other data of interest to the commonwealth.

"Age is an established factor in cancer," said Shonel Sen, a research and policy analyst at the Cooper Center's Demographics Research Group who worked on the projections. "Nearly 80 percent of cancers occur among the population ages 55 and over. As Virginia's population grows bigger and, more importantly, older, we anticipate cancer cases to be on the rise."

Using carefully developed population projections for the commonwealth and its localities, and known rates of cancer diagnosis by age from the Virginia Cancer Registry, the Demographics Research Group prepared projections for the number of new cases of breast (in females), prostate (in males) and lung cancers, as well as a combined category called "all cancers" for each decade through 2040.

"We developed these projections to complement the leading work underway at the University of Virginia Cancer Center in cancer control and population health statistics," said Qian Cai, director of the Demographics Research Group. "Employing our knowledge about Virginia demographics and expertise in population estimates and projections, we are able to develop credible forecasts of cancer incidence at state and regional levels."

Pending funding, the Demographics Research Group will develop additional projections for Virginia of incidence of other cancer types, and of deaths from cancer over the three decades in this report. In addition, three-decade projections of cancer incidence and deaths for the nation overall and for the 50 states can be developed, if funding is available.

"We believe that these projections will be helpful to health care providers, insurance companies and state and local governments, as well as informing the citizens of the commonwealth about this disease that impacts the lives of so many individuals and their families," Cai said. "Data such as this for cancer, and for other diseases, are valuable in anticipating demand for services."

More information: The Census Brief, data tables, and other resources are available here: www.coopercenter.org/demograph… projections-virginia Meredith Gunter

Provided by University of Virginia

Older people at higher risk of emergency cancer diagnosis

People over 60 are at higher risk of being diagnosed with lung or bowel cancer as an emergency in hospital than younger people, according to a Cancer Research UK-supported report , published today by BMJ Open.

06 april 2015--The researchers also found that women and less affluent people are at higher risk of an emergency lung cancer diagnosis. While being unmarried, divorced or widowed was associated with having bowel cancer diagnosed as an emergency.

The Cancer Research UK review looked at over 20 studies featuring more than 687,000 lung or bowel cancer cases, of which more than 200,000 cases were diagnosed with cancer after an emergency admission to hospital. Some were admitted after seeing a GP, while others were admitted after going to an A&E department, or directly from a hospital outpatient clinic. The researchers wanted to find out more about why so many patients are diagnosed through this emergency route, particularly as emergency-diagnosed cancers tend to have poorer survival rates.

Almost 40 per cent of lung cancers and 25 per cent of bowel cancers in England were diagnosed as an emergency in hospital between 2006 and 2010. Previous research showed that eleven per cent of lung cancer patients with an emergency diagnosis survived their cancer for at least one year, compared to 42 per cent of patients diagnosed following a GP referral under the two-week-wait system. One year survival for emergency-diagnosed bowel cancer patients was 49 per cent compared to 83 per cent for two-week-wait patients.

Lead review author Dr Liz Mitchell, Senior Research Fellow at the Leeds Institute of Health Sciences said: "It may be that some patients don't go to their GP about early cancer symptoms -especially if they live alone - or they become ill very quickly, leading to an emergency diagnosis in hospital. But our review shows that other factors such as a person's age and gender might also have an influence. Knowing more about these influences could help us to find ways of ensuring that more cancers are spotted earlier, when patients often have a better chance of survival."

Sara Hiom, director of early diagnosis at Cancer Research UK said: "We need a better understanding of why some people are having their cancer diagnosis made via an emergency admission. This is important because we know that their survival chances are lower if people are diagnosed this way. This interesting review sheds some light on the factors that could be involved. We're now funding further research on the subject and calling on the Government to ensure more cancers are diagnosed at the earliest possible stage because this can make such a difference for patients."

More information: Elizabeth D Mitchell, Benjamin Pickwell-Smith, Una Macleod. 'Risk factors for emergency presentation with lung and colorectal cancers: a systematic review. DOI: 10.1136/bmjopen-2014-006965

Provided by Cancer Research UK

Study of almost 900,000 people shows prediabetes increases the risk of cancer by 15 percent

A meta-analysis comprising 16 studies and 891,426 participants from various regions of the world shows that prediabetes increases the risk of cancer by 15%, with differing risks depending on the type of cancer. The study, published in Diabetologia (the journal of the European Association for the Study of Diabetes) is by Professor Yuli Huang, The First People's Hospital of Shunde, Daliang Town, Shunde District, China, and colleagues.

09 sept 2014--Prediabetes is a general term that refers to an intermediate stage between normoglycaemia and overt diabetes mellitus. It includes individuals with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or a combination of the two. Results to date from prospective cohort studies investigating the link between prediabetes and risk of cancer are controversial. Thus in this new study, the authors did a meta-analysis to evaluate the risk of cancer in association with the impaired fasting glucose and impaired glucose tolerance population. Of the 16 studies included, four were from Asia, 11 were from the USA and Europe, and one was from Africa.

The researchers found that prediabetes was associated with a 15% increased risk of cancer overall. The results were consistent across cancer endpoint, age, duration of follow-up and ethnicity. There was no significant difference for the risk of cancer with different definitions of prediabetes (IGT or IFG). The authors note that it has been reported that obesity, an important risk factor for diabetes, is also linked to the development of cancer. For this reason, they performed a sensitivity analysis that only included studies that adjusted for BMI in the meta-analysis. They say: "We found that, after controlling for BMI, the presence of prediabetes remained associated with an increased risk of cancer of 22%."

The risk of all cancer was also increased when a lower definition of IFG (5.6-6.9 mmol/l) was used, according to the current American Diabetes Association definition of IFG, although this definition has not been accepted by either WHO's special working group on diabetes or other international guidelines. The difference of risk of cancer was not significant between IFG defined as 5.6-6.9 mmol/l or 6.1-6.9mmol/l.

In a site-specific cancer analysis, prediabetes was significantly associated with increased risks of cancer of the stomach/colorectum (relative risk, RR 1.55), liver (RR 2.01), pancreas (RR 1.19), breast (RR 1.19) and endometrium (RR 1.60) (all statistically significant), but not associated with cancer of the bronchus/lung, prostate, ovary, kidney or bladder.

The authors say several possible mechanisms could explain the results. First, chronic hyperglycaemia and its related conditions, such as chronic oxidative stress and the accumulation of advanced glycated endproducts (that are made in conditions of excessively high blood sugar) may act as carcinogenic factors. Second, increased insulin resistance leads to increased insulin secretion, which can in turn allow cancer cells to grow and divide. Third, there could be genetic mutations which predispose individuals to an increased risk of cancer, with one recent study showing that a malfunction in a tumour suppressor gene exposed individuals to increased risk of both cancer and prediabetes.

The authors say: "These findings have important clinical and public health implications. For example, in the US population aged ≥18 years, the age-adjusted prevalence of prediabetes increased from 29% in 1999–2002 to 36% in 2007–2010. Many other countries, both developed and developing, are also seeing steep rises in the number of people with both full-blown type 2 diabetes and prediabetes. Considering the high prevalence of prediabetes, as well as the robust and significant association between prediabetes and cancer demonstrated in our study, successful intervention in this large population could have a major public health impact."

They add: "It should be noted that metformin—one of several first line therapies available to treat type 2 diabetes—is now considered as having some 'protective' anticancer properties. Notably, metformin mediates an approximately 30% reduction in the lifetime risk of cancer in diabetic patients. However, whether this is true in prediabetic individuals is not yet known. Long-term, large-scale studies of high-risk individuals, especially those with IGT or a combination of IGT and IFG, are urgently needed to explore the effects of metformin interventions on the risk of cancer in people with prediabetes."

Provided by Diabetologia

Study shows epigenetic changes can drive cancer

Cancer has long been thought to be primarily a genetic disease, but in recent decades scientists have come to believe that epigenetic changes – which don't change the DNA sequence but how it is 'read' – also play a role in cancer. In particular DNA methylation, the addition of a methyl group (or molecule), is an epigenetic switch that can stably turn off genes, suggesting the potential to cause cancer just as a genetic mutation can. Until now, however, direct evidence that DNA methylation drives cancer formation was lacking.

27 july 2014--Researchers at the USDA/ARS Children's Nutrition Research Center at Baylor College of Medicine and Texas Children's Hospital have now created a mouse model providing the first in vivo evidence that epigenetic alterations alone can cause cancer. Their report appears today in the Journal of Clinical Investigation.

"We knew that epigenetic changes are associated with cancer, but didn't know whether these were a cause or consequence of cancer. Developing this new approach for 'epigenetic engineering' allowed us to test whether DNA methylation changes alone can drive cancer," said Dr. Lanlan Shen, associate professor of pediatrics at Baylor and senior author of the study.

Shen and colleagues focused on p16, a gene that normally functions to prevent cancer but is commonly methylated in a broad spectrum of human cancers. They devised an approach to engineer DNA methylation specifically to the mouse p16 regulatory region (promoter). As intended, the engineered p16 promoter acted as a 'methylation magnet'. As the mice reached adulthood, gradually increasing p16 methylation led to a higher incidence of spontaneous cancers, and reduced survival.

"This is not only the first in vivo evidence that epigenetic alteration alone can cause cancer," said Shen. "This also has profound implications for future studies, because epigenetic changes are potentially reversible. Our findings therefore both provide hope for new epigenetic therapies and validate a novel approach for testing them."

Shen, who is also with the NCI-designated Dan L. Duncan Cancer Center at Baylor, predicts that this new approach will be widely useful because in addition to p16, there are many other genes and diseases other than cancer that are connected to epigenetics (such as neurodevelopmental diseases, obesity and diabetes). Just as genetic engineering has become a standard approach for studying how genetic mutations cause disease, epigenetic engineering will now enable functional studies of epigenetics.

"This opens up the door for a whole new paradigm of how to understand tumorigenesis. If we can identify epigenetic changes that predispose people to cancer, these may actually be treatable or preventable, so this opens up a lot of optimism in new ways to deal with cancer," said Dr. Robert Waterland, associate professor of pediatrics at Baylor, who was also involved in the study.

Provided by Baylor College of Medicine

Scientists map one of most important proteins in life—and cancer

Scientists reveal the structure of one of the most important and complicated proteins in cell division – a fundamental process in life and the development of cancer – in research published in Nature today.

21 july 2014--Images of the gigantic protein in unprecedented detail will transform scientists' understanding of exactly how cells copy their chromosomes and divide, and could reveal binding sites for future cancer drugs.

A team from The Institute of Cancer Research, London, and the Medical Research Council Laboratory of Molecular Biology in Cambridge produced the first detailed images of the anaphase-promoting complex (APC/C).

The APC/C performs a wide range of vital tasks associated with mitosis, the process during which a cell copies its chromosomes and pulls them apart into two separate cells. Mitosis is used in cell division by all animals and plants.

Discovering its structure could ultimately lead to new treatments for cancer, which hijacks the normal process of cell division to make thousands of copies of harmful cancer cells.

In the study, which was funded by Cancer Research UK, the researchers reconstituted human APC/C and used a combination of electron microscopy and imaging software to visualise it at a resolution of less than a billionth of a metre.

The resolution was so fine that it allowed the researchers to see the secondary structure – the set of basic building blocks which combine to form every protein. Alpha-helix rods and folded beta-sheet constructions were clearly visible within the 20 subunits of the APC/C, defining the overall architecture of the complex.

Previous studies led by the same research team had shown a globular structure for APC/C in much lower resolution, but the secondary structure had not previously been mapped. The new study could identify binding sites for potential cancer drugs.

Each of the APC/C's subunits bond and mesh with other units at different points in the cell cycle, allowing it to control a range of mitotic processes including the initiation of DNA replication, the segregation of chromosomes along protein 'rails' called spindles, and the ultimate splitting of one cell into two, called cytokinesis. Disrupting each of these processes could selectively kill cancer cells or prevent them from dividing.

Dr David Barford, who led the study as Professor of Molecular Biology at The Institute of Cancer Research, London, before taking up a new position at the Medical Research Council Laboratory of Molecular Biology in Cambridge, said:

"It's very rewarding to finally tie down the detailed structure of this important protein, which is both one of the most important and most complicated found in all of nature. We hope our discovery will open up whole new avenues of research that increase our understanding of the process of mitosis, and ultimately lead to the discovery of new cancer drugs."

Professor Paul Workman, Interim Chief Executive of The Institute of Cancer Research, London, said: "The fantastic insights into molecular structure provided by this study are a vivid illustration of the critical role played by fundamental cell biology in cancer research.

"The new study is a major step forward in our understanding of cell division. When this process goes awry it is a critical difference that separates cancer cells from their healthy counterparts. Understanding exactly how cancer cells divide inappropriately is crucial to the discovery of innovative cancer treatments to improve outcomes for cancer patients."

Dr Kat Arney, Science Information Manager at Cancer Research UK, said "Figuring out how the fundamental molecular 'nuts and bolts' of cells work is vital if we're to make progress understanding what goes wrong in cancer cells and how to tackle them more effectively. Revealing the intricate details of biological shapes is a hugely important step towards identifying targets for future cancer drugs."

More information: Molecular architecture and mechanism of the anaphase-promoting complex, Nature, DOI: 10.1038/nature13543

Provided by Cancer Research UK

Cancer risk for aging Baby Boomers

As 10,000 baby boomers reach 65 each day, the incidence of cancer is increasing, estimated to increase by 67% between 2010 and 2030, bringing attention to the nation's response to cancer care. Cancer is diagnosed at a higher rate, accounts for more survivors, and results in more deaths than in younger patients.

03 dec 2013--"The increase in the number of older adults, the association of cancer with aging, the workforce shortage, and the financial stressors across the health care system and family networks all contribute to a crisis in cancer care that is most pronounced in the older population," wrote three members of the Institute of Medication Committee on Improving the Quality of Cancer Care: Addressing the Challenges of an Aging Population in an editorial published In JAMA, The Journal of the American Medical Association.

"Often caregiving falls to a family member who is also aging," noted Mary D. Naylor, PhD, FAAN, RN, the Marian S. Ware Professor in Gerontology and the Director of the NewCourtland Center for Transitions and Health and a member of the committee. As the originator of the Transitional Care Model, Dr. Naylor has addressed the unique needs of older adults and their caregivers, offering evidence-based solutions. "We need to address the physical, psychological, financial and emotional tolls on caregivers by developing more effective ways to prepare and support them."

The authors noted potential improvements to cancer care among older persons, including:

• Passing new laws extending the time period for clinical trials (similar to laws passed for pediatric patients) in order to include more older adults, noting that "although the majority of patients with cancer and cancer survivors are older adults, historically they have been and continue to be underrepresented in all types of cancer trials. The result may be that drugs are tested on a younger and fitter population that belies potential health risks to older people who may also have more than one condition;
• Letting the patients decide what works. The authors recommended "publicly reported, robust measures of patient reported outcomes meaningful for this population;" and
• Establishing a national workforce commission "to plan for the challenges of an aging population and the complexity of care required by older adults with cancer, including a workforce that values multidisciplinary teams and geriatrics principles.

More information: "Improving the Quality of Cancer Care in an Aging Population: Recommendations From an IOM Report." Arti Hurria, MD; Mary Naylor, PhD, RN; Harvey Jay Cohen, MD. JAMA. 2013;310(17):1795-1796. DOI: 10.1001/jama.2013.280416.

Provided by University of Pennsylvania School of Nursing

Simple, two-question survery accurately screens cancer patients for depression

Cancer patients can be accurately screened for major depression with a simple two-question survey, according to a study presented Sept. 23 at the American Society for Radiation Oncology's 55th Annual Meeting.

24 sept 2013--The two-question screening test proved to be as accurate as a longer nine-question screening test.

The study was presented at plenary session by William Small, Jr., MD, FASTRO, chair of the Department of Radiation Oncology of Loyola University Medical Center.

"We found that a two-question survey can effectively screen for depression," Small said. "We hope this will prompt more centers to screen for depression, and to refer patients for treatment when necessary."

The two-question survey asks whether, over the last two weeks, a patient has experienced:

• Little interest or pleasure in doing things
• Feeling down, depressed or hopeless

For each question, the patient can answer not at all (worth zero points); several days (1 point); more than half the days (two points); or nearly every day (3 points). A patient who scores a total of three or more points on both questions is considered to be at risk for being depressed.

The study included 455 cancer patients receiving radiation therapy at 37 centers in the United States. Patients were surveyed before or within two weeks of receiving their first radiation treatment. Sixteen percent screened positive for depression.

For comparison purposes, patients who screened positive were administered an in-depth telephone interview known as SCID, which is considered the gold standard for diagnosing depression. A random sample of patients who screened negative for depression also underwent the SCID interview. (SCID stands for Structured Clinical Interview for DSM IV Disorders.)

The two-question survey consists of the first two questions of the nine-question Patient Health Questionnaire. The study found that the abbreviated two-question survey was just as accurate as the full nine-question survey. In statistical terms, both surveys had an "area under the curve" of 0.83. (A 100 percent accurate test would have an area under the curve of 1.0.)

The two-question screening test was more accurate than two other screening tests researchers administered. These less-accurate screening tests are the Hopkins Symptom Checklist (0.79 area under the curve) and the National Comprehensive Cancer Network Distress Thermometer (0.60 area under the curve).

The study found that 78 percent of centers routinely screen patients for depression at the radiation therapy facility, with 51 percent screening at the initial visit. Mental health services were available at 68 percent of radiation therapy facilities. However, 67 percent of sites offered only social workers; 17 percent offered psychologists and 22 percent offered psychiatrists.

"We think the results of this large, nationwide trial will have a major impact on how cancer patients are screened for depression," Small said.

More information: The study is titled "Two Item Questionnaire Effectively Screens for Depression in Cancer Patients Receiving Radiotherapy."

Provided by Loyola University Health System

Major changes urged for cancer screening and treatment

To address the growing problem of people being overdiagnosed and overtreated for cancer, a group of scientists convened by the National Cancer Institute and chaired by a UC San Francisco breast cancer expert is proposing a major update of the way the nation approaches diseases now classified as "cancer."

30 july 2013--The "Viewpoint" article will be published online Monday, July 29, in the Journal of the American Medical Association.

When cancer screening programs were widely initiated three decades ago, medical knowledge of the disease was more simplistic. The intent was to detect cancer at its earliest stages to reduce illness and mortality, but in fact early diagnosis has not led to a proportional decline in serious disease and death, the scientists write in the JAMA commentary.

Instead, screening programs are identifying not only malignant cancers, but also slow-growing, low-risk lesions, and sweeping them into the same treatment process. As a result, patients are being diagnosed and treated for forms of cancer that might never actually harm them – a phenomenon that's been termed overdiagnosis, which translates to "too much medicine."

Now, with the advancement of scientific understanding of the biology of cancer, the authors say it is time for significant changes in practice and policy.

"By recognizing that cancer is not one disease, but a number of different diseases, we can individualize our treatment based on biology and avoid overtreatment," said panel chair Laura J. Esserman, MD, MBA, director of the Carol Franc Buck Breast Care Center at the UCSF Helen Diller Family Comprehensive Cancer Center. "The goal going forward is to personalize screening strategies, and focus screening policies on the conditions that are most likely to result in aggressive illness and death."

The authors recommend creation of a new classification for tumors that are indolent (unlikely to cause patients harm). For example, ductal carcinoma of the breast—currently considered the earliest form of breast cancer—would no longer be called cancer. The authors also call for the formation of registries for lesions with low potential for malignancy, and for a multidisciplinary approach across pathology, imaging, surgery and other medical specialties "to revise the taxonomy of lesions now called cancer."

The key, they say, is to improve screening strategies to avoid overtreating tumors that would not be lethal, or that would not even have come to medical attention.

"Although our understanding of the biology of cancer has changed dramatically, perceptions on the part of the public, and among many physicians, have not yet changed," Esserman said. "Cancer is still widely perceived as a diagnosis with lethal consequences if left untreated."

The JAMA article is comprised of recommendations from a working group formed last year during a meeting convened by the National Cancer Institute. The group was charged with developing a strategy to improve current approaches to cancer screening and prevention.

The commentary was co-written by Ian M. Thompson, MD, professor at the University of Texas Health Science Center at San Antonio; and Brian Reid, MD, PhD, director of the Seattle Barrett's Esophagus Program and member of the Human Biology Division at the Fred Hutchison Cancer Research Center in Seattle.

The three authors served as chairs of the NCI working group.

Overdiagnosis is occurring across many medical conditions, but is particularly common in breast cancer, lung cancer, prostate, thyroid cancer and melanoma, said the authors.

They cite DCIS, or ductal carcinoma of the breast, and Barrett's esophagus as illustrations of how the detection and surgical removal of what have been called precancerous lesions have failed to lead to lower rates of invasive cancer.

By contrast, the authors said, colon and cervical cancer serve as examples of "effective screening programs in which early detection and removal of precancerous lesions have reduced incidence as well as late-stage disease."

Cancer screening should have three important missions, the authors write: To detect disease that would ultimately harm the patient; to uncover tumors that benefit from intervention; and to detect disease that is more likely to be cured or better treated when spotted early.

Optimal screening frequency depends on a cancer's growth rate. If a cancer is fast growing, screening is less likely to be effective. "If a cancer is slow growing but progressive, with a long latency and a precancerous lesion, screening is ideal and less frequent screening (eg.10 years for colonoscopy) may be effective," the authors said.

The recommendations include:

• Recognize that screening will identify indolent cancers.
• Change terminology and omit the word "cancer" from premalignant/indolent conditions;
• Convene a multidisciplinary body to revise the current taxonomy of cancer and to create reclassification criteria for indolent conditions;
• Create observational registries for lesions with low potential for malignancy – generate the data to provide patients and their doctors "with confidence to select less invasive interventions;"
• Develop, validate and adopt molecular diagnostic tools that identify indolent or low-risk lesions;
• Mitigate overdiagnosis: appropriately reduce frequency of screening exams while focusing on high-risk populations, and raise the threshold for patients being recalled for re-testing and biopsy.

"Although no physician has the intention to overtreat or overdiagnose cancer, screening and patient awareness have increased the chance of identifying a spectrum of cancers, some of which are not life threatening," the authors wrote. "The ultimate goal is to preferentially detect consequential cancer while avoiding detection of inconsequential disease."

Provided by University of California, San Francisco