As Americans Get Heavier, Obesity-linked Cancers May Strike Earlier

Linda Carroll wrote . . . . . . . . .

Increasing numbers of middle-aged Americans appear to be developing cancers that can be associated with obesity, new data suggest.

And the increase in these cancers among 50- to 64-year-olds parallels the rising rates of obesity, researchers say.

In their analysis of more than six million cancer cases, researchers found that obesity-associated cancers appeared to be shifting to younger people, including those under 50, according to the report published in JAMA Network Open.

“Obesity creates a state of constant low-grade inflammation, as well as multiple growth stimulating factors, all of which can accelerate the development of cancer,” explained the study’s lead author, Siran Koroukian, an associate professor in the department of population and quantitative Health Sciences at the Case Western Reserve University School of Medicine and director of the Population Cancer Analytics Shared Resource at Case Comprehensive Cancer Center, both in Cleveland, Ohio.

It’s possible that people can impact their cancer risk by watching their weight, Koroukian said in an email. “There is some evidence that weight loss (among those who are obese) can prevent the development of cancer,” she added. “The most important strategy is maintaining a normal weight.”

To take a closer look at the impact of obesity on cancer risk, Koroukian and her colleagues turned to data from the Surveillance, Epidemiology and End Results 18 (SEER18) database, focusing on cancer cases diagnosed from 2000 through 2016. The database is nationally representative and covers geographically diverse regions of the country.

The researchers looked for trends in the percentage of cases diagnosed in three age groups: 20-49, 50-64 and 65 and older.

Obesity-associated cancers considered by the researchers included myeloma, female breast cancer and cancers of the colon and rectum, gallbladder, esophagus, stomach, liver, pancreas, uterus, kidney and thyroid.

Among the more than 6 million cases, 43.6% were obesity-associated cancers.

When the researchers analyzed their data, they found a greater increase in the odds for an obesity-associated cancer compared to non-obesity associated cancers in the 50- to 64-year age group, but a decrease for older individuals.

While it looks like the growing rates of obesity are driving up obesity-associated cancers, this study can’t prove that, said Dr. Daniel Labow, chair of surgical oncology at the Mount Sinai Health System.

A major limitation of the study, he pointed out, is that the SEER database does not include information on body mass index, so it’s impossible to know whether these cancers are actually occurring in obese individuals.

“There are so many other factors that could be affecting trends and movements in cancer incidence,” Labow said. For example, the trend could be explained by the kinds of foods people are eating, he added.

“A high animal fat diet and lots of processed foods certainly could be contributing,” Labow said. Nevertheless, “obesity is not good for many different things so we should be working on decreasing it and it would be nice if we also saw a downstream trend of reduction of cancers,” he added.

Dr. Jian-Min Yuan agrees that there could be many factors that changed over time besides obesity. “A person who was a teen in the late 70s to early 80s, might have experienced a lifestyle change,” Yuan said. “Maybe they were more stressed. Maybe they ate a lot more meat and consumed less fiber. They could have consumed more alcohol. Their sleeping patterns might have changed in that era because of a much faster modern lifestyle.”

Source: Reuters


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Researchers Take Key Step Toward Cancer Treatments that Leave Healthy Cells Unharmed

Researchers have opened up a possible avenue for new cancer therapies that don’t have the side effects that oftentimes accompany many current cancer treatments by identifying a protein modification that specifically supports proliferation and survival of tumor cells.

Depending on the kind of cancer and the type of treatment, a patient might suffer from many side effects, including anemia, loss of appetite, bleeding, bruising, constipation, delirium, diarrhea, fatigue, hair loss, nausea, sexual issues or bladder problems.

Scientists at Oregon State University, the University of Central Florida and New York University made the protein-modification discovery while studying neurofibromatosis type 2. The condition, commonly known as NF2, is characterized by the development of tumors of the nervous system called schwannomas.

“The hallmark of tumor cell behavior is their uncontrolled growth,” said Maca Franco, professor of biochemistry and biophysics in OSU’s College of Science. “Tumors cells need to constantly produce energy and building blocks to replicate.”

Researchers led by Franco and Oregon State undergraduate student Jeanine Pestoni found that schwannoma cells produce an oxidant and nitrating agent, peroxynitrite, which modifies an amino acid, tyrosine, in proteins.

When tyrosine becomes nitrated in specific proteins, an effect is the reprogramming of the tumor cells’ metabolism, enabling them to proliferate.

“To sustain persistent growth, tumor cells change the way they produce energy and building blocks and present a signature metabolic phenotype that differs from that of normal cells,” Franco said. “We discovered that peroxynitrite, the most powerful oxidant produced by cells, controls the metabolic changes that occur in tumor cells of the nervous system and supports their growth. We believe that there are specific proteins that when they become nitrated acquire a new function they did not have before, and this new function may control tumor growth.”

Peroxynitrite is produced at high levels in “pathological conditions,” she said – such as those found in tumors – but not in normal tissues.

“This opens up the exciting possibility of targeting peroxynitrite production exclusively in tumor cells as a new therapeutic strategy for the treatment of tumors of the nervous system, with minimal to no side effects on normal tissues,” Franco added. “We are uncovering a completely new category of targets for the treatment of solid tumors, and not only tumors of the nervous system – it may have broader implications for the treatment of several cancer types. We can go after proteins that usually aren’t modified in normal cells; we can target those modified proteins with inhibitors that don’t affect normal cells, hopefully developing a treatment with minimal side effects.”

The National Institutes of Health and the Office of the Assistant Secretary of Defense for Health Affairs supported this research.

Findings were published in the Journal of Biological Chemistry.

Source : Oregon State University

Cancer Research Points to Key Unknowns about Popular “Anti-aging” Supplements

Helen Shen wrote . . . . . . . . .

As the world’s aging population grows rapidly, so has its appetite for health tips, tricks and products that could help guard against the ravages of time. Among countless dietary supplements—vitamins, minerals and other products—some people have pinned their hopes on a molecule called nicotinamide adenine dinucleotide (NAD), a key player in the cellular production of energy. Often written as NAD+, the name of its oxidized form, the molecule participates in a host of metabolic pathways and is involved in other important processes, such as DNA repair. NAD+ levels naturally decline as people and animals age, and this loss has been proposed as contributing to the underlying physiology of aging.

Studies show that boosting NAD+ levels can extend life span in yeast, worms and mice. Animal research also indicates NAD+’s promise for improving several aspects of health. Raising levels of the molecule in old mice appears to rejuvenate mitochondria—the cell’s energy factories, which falter over time. Other mouse studies have demonstrated benefits such as improved cardiovascular function, enhanced muscle regeneration and better glucose metabolism with NAD+ supplementation.

Banking on such results, multiple companies currently sell dietary supplements containing NAD+ precursors such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN). NR supplements, in particular, have attracted buzz for the scientific star power associated with two major suppliers, ChromaDex and Elysium Health. The companies’ research advisers hail from institutions such as Stanford, Harvard and Columbia University. Elysium’s scientific advisory board currently boasts eight Nobel laureates.

But the NR business and some scientists involved have attracted their share of criticism as well. Unlike drugs, dietary supplements are lightly regulated by U.S. authorities, allowing them to be sold before research confirms their safety and effectiveness in humans. Recent clinical trials funded by ChromaDex and Elysium show that adults taking NR-containing supplements for six to eight weeks experience increased levels of NAD+ in their blood without serious side effects. But researchers are still working to prove that NR can actually improve human health—a sticking point for critics and an issue acknowledged by the companies themselves.

“Not everything that works in mice works in humans, which is why it’s critical to do the rigorous human trials,” says Leonard Guarente, a co-founder of Elysium and its chief scientist. The company is studying the effectiveness of its NR-containing supplement for a number of conditions in people, including kidney injury and fatty liver. Early this year, Elysium published a small trial showing that its product could potentially slow the neurodegenerative disease amyotrophic lateral sclerosis. ChromaDex’s NR supplement is also the subject of many clinical trials, with the company recently sponsoring a study of its effects on cognitive function, mood and sleep in people older than 55.

For very different reasons, NAD+ has also attracted a wave of attention from cancer researchers. Recent studies suggest that cancer cells of many types depend on NAD+ to sustain their rapid growth and that cutting off the NAD+ supply could be an effective strategy for killing certain cancers. The data from these studies paint a more complicated picture of NAD+ and raise new questions about the diverse ways taking an NAD+-boosting supplement might influence health. “It might still slow down the aging part, but it might fuel the cancer part,” says Versha Banerji, a clinician-scientist at the University of Manitoba. “We just need to figure out more about the biology of both of those processes, to figure out how we can make people age well and also not get cancer.”

In a Nature Cell Biology study in February scientists reported a newly discovered role for NAD+ metabolism at the intersection of cellular aging and cancer—specifically, in a process called cellular senescence. Senescence occurs when aging, damaged cells stop dividing. The process can help suppress cancer, but it leads cells to produce inflammatory molecules that can also promote cancer growth under certain conditions. In the Nature Cell Biology study, Rugang Zhang of the Wistar Institute, and his colleagues found that in cells entering senescence, rising levels of NAMPT (a major NAD+-producing enzyme in mammals) encourage the release of inflammatory and potentially protumor molecules. Consistent with those findings, mice genetically predisposed toward pancreatic cancer developed more precancerous and cancerous growths when they consumed the NAD+ precursor NMN. Zhang says more research is needed to fully understand the role of NAD+ in cancer, but he adds that “we should be cautious and bear in mind the potential downside of NAD+ supplementation as a dietary approach for antiaging.”

Zhang’s work is part of a growing body of research that has drawn attention to NAD+ metabolism in cancer, particularly involving NAMPT. Compared with healthy tissues, elevated NAMPT levels have been reported in several human cancers including colorectal, ovarian, breast and prostate cancers. In studies in animals and cells, drugs that inhibit NAMPT have shown promise in killing cancer cells or enhancing the effectiveness of other cancer therapies.

In 2016 researchers at Washington University School of Medicine in St. Louis found that among people with glioblastoma—an aggressive form of brain cancer—tumors with higher NAMPT levels correlated with shorter survival times. When human glioblastoma cells were implanted in mice, the cells proliferated and established new tumors. But when researchers suppressed NAMPT in these cells before implantation, they later saw reduced brain-tumor formation and increased survival in the mice—suggesting that glioblastoma cells depend on NAMPT and NAD+ to thrive.

What might this result say about NAD+-boosting supplements? “There’s a lot of buzz about taking NAD+ precursors for their antiaging effects, which is based on a lot of great science,” said Albert Kim, senior author of the 2016 study, in a School of Medicine press release “I don’t know if taking NAD+ precursors makes existing tumors grow faster, but one implication of our work is that we don’t yet fully understand all of the consequences of enhancing NAD+ levels.”

These emerging questions are not ruffling makers of NR supplements. “I’m not losing sleep over this,” says Charles Brenner, chief scientific advisor for ChromaDex. Reports of higher-than-normal NAMPT levels in many cancers do not prove that high NAD+ levels actually promote cancer growth, he notes. He contends that studies that kill cancer cells by suppressing the NAD+-producing enzyme also do not properly address the issue. “Whether low NAD+ would block cancer and whether high NAD+ would promote cancer are two separate questions,” he says.

Indeed, Zhang’s study is one of the first to directly show that providing supplemental NAD+, via the precursor NMN, was associated with increased cancerous growths in mice. But Elysium’s Guarente is skeptical of the data, arguing that Zhang’s study showed a small effect in a small number of animals and that it has yet to be replicated by other groups. “I don’t think the evidence is there at all to say that raising NAD+ levels would favor cancer,” Guarente says.

At the moment, the idea that elevating NAD+ levels could fuel cancer growth remains a hypothesis, but it is one that has attracted considerable attention. Cancer cells have high metabolic needs, including processes requiring NAD+. And many types of cancer cells boost NAD+-making enzymes and then die when those enzymes are blocked by drugs. “We know that they like NAD+, but it’s too early to say, if you add NAD+, whether they will grow really fast,” says Shashi Gujar, a cancer immunologist at Dalhousie University. “Many labs are working to figure that out.”

The answer may not be a single or straightforward one. NAD+ is a ubiquitous and fundamental molecule, involved in many biological pathways and cellular operations. Its ingestion could lead to a mix of positive and negative outcomes, the balance of which might depend on context. NAD+ precursors, consumed orally, may be taken up by some tissues more than others. And different cell types are known to employ distinct metabolic programs, which could lead to tissue-specific responses to NAD+.

Like the tissues from which they arise, cancers are diverse in their cellular ways—and at least some run counter to the “cancer fuel” hypothesis of NAD+. A 2014 study, for instance, reported that in a mouse model of liver cancer, inhibiting NAD+ production was a key step by which an errant gene caused DNA damage and tumor formation. In this case, feeding NR to the mice actually helped protect against these harmful effects.

Together these findings do not necessarily point to ready answers for consumers interested in NR or NMN supplements, so much as they highlight questions for scientists to address in the coming years. “I would say that given that many people are taking these supplements for health benefits, a study of what these do to cancer risk or existing cancer biology is warranted,” says Matthew Vander Heiden, a clinician-scientist at the Massachusetts Institute of Technology’s Koch Institute for Integrative Cancer Research.

The need for more evidence is a sentiment that is shared by others. “There is tremendous interest in the NAD+ field right now,” Gujar says. “And I’m pretty sure sooner or later, we will have the evidence to answer this.”

Source : Scientific American


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Results from a Preliminary Human Trial of Nicotinamide Riboside Supplementation . . . . . . .

Exercise Improves Anxiety And Mood In Older Adults Undergoing Chemotherapy

Although we know that exercise improves anxiety and mood problems in younger people with cancer, few studies have looked at the effects of exercise on older adults with cancer. Since most new cancer cases occur in adults aged 60 or older, a team of researchers from the University of Rochester Medical Center and other institutions designed a study to learn more.

Their study appeared in the Journal of the American Geriatrics Society (JAGS).

Having cancer increases the chances of people experiencing anxiety and mood issues, which can affect emotional and social well-being. In turn, this may lead people to discontinue cancer treatments—which can mean shortening their survival.

Chemotherapy can benefit older adults with cancer, even though older people receiving this type of treatment often experience higher rates of dangerous side effects than younger people do. Older adults often experience anxiety and other mood disorders during their treatment for cancer, too—and treating those problems with medications can often cause potentially dangerous side effects.

What’s more, many anti-anxiety medications such as benzodiazepines and antidepressants are listed in the American Geriatrics Society (AGS) Beers Criteria® as being potentially inappropriate for older adults. That’s why it is desirable to seek alternative treatments that are safe and effective at improving anxiety, mood disturbances, and emotional and social well-being, including treatments that don’t rely on medications. For example, several studies have been conducted to examine the relationship between exercise and mood in cancer survivors and most have shown positive results.

The researchers in the new JAGS study examined the Exercise for Cancer Patients (EXCAP) program, a home-based, low- to moderate-intensity aerobic and resistance exercise program. In the study, those who were assigned to the EXCAP program received an exercise kit. It contained a pedometer, three exercise bands (medium, heavy, extra heavy), and an instruction manual.

During the program, participants increased the length and intensity of their workouts over time. For example, participants received an individually tailored, progressive walking routine, and they wore a pedometer and recorded their daily steps over six weeks, starting on their first day of chemotherapy treatment. They were encouraged to gradually increase their steps by five to 20 percent every week. For resistance exercise, they performed exercises with therapeutic exercise bands. Participants were given individually-tailored workout plans that encouraged them to perform 10 required exercises (such as squats and chest presses) and four optional exercises daily. Participants were also encouraged to increase the intensity and number of repetitions of resistance band exercises gradually over the course of the program.

The researchers concluded that a low- to moderate-intensity home-based exercise program improved anxiety, mood, and social and emotional well-being for older patients with cancer who received chemotherapy treatments.

The researchers also noted that in the study, the people who benefited the most from the exercise program were older adults who received chemotherapy and started off with worse anxiety, mood, and social and emotional well-being.

This summary is from “Effects of a home-based exercise program on anxiety and mood disturbances in older adults with cancer receiving chemotherapy.” It appears online ahead of print in the Journal of the American Geriatrics Society.

Source: HealthinAging.org


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Study Suggests Possible Link between Sugary Drinks and Cancer

A study published by The BMJ reports a possible association between higher consumption of sugary drinks and and an increased risk of cancer.

While cautious interpretation is needed, the findings add to a growing body of evidence indicating that limiting sugary drink consumption, together with taxation and marketing restrictions, might contribute to a reduction in cancer cases.

The consumption of sugary drinks has increased worldwide during the last few decades and is convincingly associated with the risk of obesity, which in turn is recognised as a strong risk factor for many cancers. But research on sugary drinks and the risk of cancer is still limited.

So a team of researchers based in France set out to assess the associations between the consumption of sugary drinks (sugar sweetened beverages and 100% fruit juices), artificially sweetened (diet) beverages, and risk of overall cancer, as well as breast, prostate, and bowel (colorectal) cancers.

Their findings are based on 101,257 healthy French adults (21% men; 79% women) with an average age of 42 years at inclusion time from the NutriNet-Santé cohort study.

Participants completed at least two 24-hour online validated dietary questionnaires, designed to measure usual intake of 3,300 different food and beverage items and were followed up for a maximum of 9 years (2009-2018).

Daily consumption of sugary drinks (sugar sweetened beverages and 100% fruit juices) and artificially sweetened (diet) beverages were calculated and first cases of cancer reported by participants were validated by medical records and linked with health insurance national databases.

Several well known risk factors for cancer, such as age, sex, educational level, family history of cancer, smoking status and physical activity levels, were taken into account.

Average daily consumption of sugary drinks was greater in men than in women (90.3 mL v 74.6 mL, respectively). During follow-up 2,193 first cases of cancer were diagnosed and validated (693 breast cancers, 291 prostate cancers, and 166 colorectal cancers). Average age at cancer diagnosis was 59 years.

The results show that a 100 mL per day increase in the consumption of sugary drinks was associated with an 18% increased risk of overall cancer and a 22% increased risk of breast cancer.

When the group of sugary drinks was split into fruit juices and other sugary drinks, the consumption of both beverage types was associated with a higher risk of overall cancer. No association was found for prostate and colorectal cancers, but numbers of cases were more limited for these cancer locations.

In contrast, the consumption of artificially sweetened (diet) beverages was not associated with a risk of cancer, but the authors warn that caution is needed in interpreting this finding owing to a relatively low consumption level in this sample.

Possible explanations for these results include the effect of the sugar contained in sugary drinks on visceral fat (stored around vital organs such as the liver and pancreas), blood sugar levels, and inflammatory markers, all of which are linked to increased cancer risk.

Other chemical compounds, such as additives in some sodas might also play a role, they add.

This is an observational study, so can’t establish cause, and the authors say they cannot rule out some misclassification of beverages or guarantee detection of every new cancer case.

Nevertheless, the study sample was large and they were able to adjust for a wide range of potentially influential factors. What’s more, the results were largely unchanged after further testing, suggesting that the findings withstand scrutiny.

These results need replication in other large scale studies, say the authors.

“These data support the relevance of existing nutritional recommendations to limit sugary drink consumption, including 100% fruit juice, as well as policy actions, such as taxation and marketing restrictions targeting sugary drinks, which might potentially contribute to the reduction of cancer incidence,” they conclude.

Source: BMJ