alcohol

Should we be drinking less?

Source: www.nytimes.com
Author: Anahad O’Connor

Can a daily drink or two lead to better health?

For many years, the federal government’s influential dietary guidelines implied as much, saying there was evidence that moderate drinking could lower the risk of heart disease and reduce mortality.

But now a committee of scientists that is helping to update the latest edition of the Dietary Guidelines for Americans is taking a harder stance on alcohol. The committee said in a recent conference call that it plans to recommend that men and women who drink limit themselves to a single serving of wine, beer or liquor per day. Do not drink because you think it will make you healthier, the committee says: It won’t. And it maintains that drinking less is generally better for health than drinking more.

That message is a departure from previous guidelines, which since 1980 have defined “moderate” drinking as up to two drinks a day for men and one for women. Government agencies have also long defined a standard drink as 12 ounces of regular beer, five ounces of wine, or one and a half ounces of distilled spirits (40 percent alcohol), amounts often exceeded in Americans’ typical “drink.”

Between 1990 and 2010, many editions of the guidelines, which are updated every five years, discouraged heavy drinking and warned pregnant women and people with certain medical conditions not to drink. But they also noted that moderate drinking was linked to fewer heart attacks and lower mortality. The 2010 guidelines mentioned that moderate drinking may even “help to keep cognitive function intact with age.”

The new recommendation would be a victory for experts who have long questioned the health halo around moderate drinking. They say that studies showing it can protect health are deeply flawed, and that any potential cardiovascular benefits would be outweighed by the fact that alcohol is a leading preventable cause of cancer. According to the National Cancer Institute, even one drink a day increases the risk of breast, esophageal and oral cancer.

“This is significant because the committee has finally gotten away from this idea that a small amount of alcohol is good for you,” said Thomas Gremillion, the director of food policy at the Consumer Federation of America, a public interest group that has pushed for cancer warnings on alcohol. “They’re really taking a stand and saying drinking less is always better. That’s the right message and I think they deserve credit for making that change.”

The new advice is not yet final. The advisory panel is expected to include it in a report that it will release publicly in mid-July and submit to the Department of Agriculture and the Department of Health and Human Services. Those two agencies are scheduled to publish the official dietary guidelines later this year.

If accepted, the new recommendation would make the United States the latest country to issue stricter guidelines on alcohol consumption. In recent years, Britain, Australia, France and other countries have issued new guidelines lowering their recommended limits on daily and weekly alcohol intake. Health authorities in those countries have said that recent evidence suggests consuming less alcohol is safer and that even one drink a day increases cancer risk.

The scientific debate over moderate drinking dates at least back to the 1970s, when researchers in California noticed that teetotalers seemed to have more heart attacks than people who drank moderately. In the decades that followed, many observational studies looking at large populations documented what is known as a J-shaped curve between alcohol and mortality from all causes, especially heart disease: Mortality rates dipped for moderate drinkers compared to nondrinkers and then climbed higher among people whose intake exceeded one or two drinks daily.

But observational studies can show only correlations, not causation. And they have other limitations. One major confounding factor is that socioeconomic status is a strong predictor of health and life span — and it tracks closely with drinking levels. Studies show that compared to heavy drinkers and abstainers, people who drink moderately tend to be wealthier and have higher levels of education. They tend to have better health care, exercise more, eat healthier diets, and have less obesity.

One study that compared nondrinkers to moderate drinkers — defined as having two drinks daily for men and one for women — found that 27 out of 30 well established risk factors for heart disease were “significantly more prevalent” among nondrinkers. Rather than causing better health, in other words, moderate drinking may be a marker for higher socioeconomic status and other lifestyle factors that promote a longer life.

Another problem with observational studies is selection bias. In some large studies, people categorized as “nondrinkers” may actually be former heavy drinkers, or they may have health issues that cause them not to imbibe. Studies have found that nondrinkers have higher rates of physical disabilities, psychiatric problems and pre-existing illnesses. When rigorous studies take these factors into account, they find that the protective effect of moderate drinking disappears.

“The appearance of protection vanishes like the mist on an autumn day as the sun comes up,” said Timothy Stockwell, an alcohol researcher and director of the Canadian Institute for Substance Use Research at the University of Victoria. “All of these thousands of studies, when you do a forensic examination of them, most of them have these horrendous flaws and are open to these systematic biases.”

One way to get around these limitations is through genetic studies. Some people carry a genetic variant that disrupts their ability to metabolize alcohol, causing them to develop skin flushing, irritation and other unpleasant symptoms when they drink alcohol. As a result, they tend to abstain or drink very little. If alcohol was good for heart health, these people should in theory have more heart disease compared to others. Instead, as one large analysis published in BMJ in 2014 found, they have “a more favorable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant.”

The study concluded: “This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.”

Not everyone agrees that the health benefits of moderate drinking are illusory. Alcohol has blood-thinning properties, and red wine in particular contains polyphenols that have beneficial effects on the microbiome, said Dr. Erik Skovenborg, a family doctor and member of the International Alcohol Forum, an international group of scientists who study alcohol and health. Alcohol also raises HDL cholesterol, often referred to as the “good” kind, though recent studies have cast doubt on it being cardioprotective.

Dr. Skovenborg said the observational data makes it clear that moderate drinking is more than a marker for a healthy lifestyle.

“In these studies you have many participants that have all the healthy lifestyle factors,” he said, “and if you add moderate alcohol consumption on top of that, it increases the benefits regarding longer life and fewer health problems.”

Dr. Skovenborg said his general advice to patients who drink is to follow the Mediterranean tradition: Have a little wine with your meals, drink slowly, enjoy it, and don’t drink to get drunk. Exercise regularly, avoid smoking, eat nutritious foods, and maintain a normal weight. “It’s a pattern of things you should be doing, not just one thing,” he added.

Showing definitively that moderate drinking protects heart health requires doing a lengthy clinical trial, one that randomly assigns some people to have a drink daily and others to abstain. In 2014, the National Institutes of Health launched a clinical trial designed to do just that. But it was shut down in 2018 after a New York Times investigation revealed that N.I.H. officials had lobbied beer and liquor companies for funding and suggested that the results of the trial would support moderate drinking. As it turns out, experts have long raised concerns about industry influence on alcohol studies.

Members of the advisory committee declined to comment on their recommendations until their report is released. Dr. Stockwell said he agreed with the one-drink-a-day recommendation but he would word it slightly differently. “I’d probably say seven drinks a week for men and women and no more than two drinks on one day,” he said. “I would have a little flexibility.”

Study: Regular drinkers can curb chance of getting alcohol related diseases with exercise

Source: www.express.co.uk
Author: Richard Percival

The scientists revealed that heavier drinkers needed to produce greater physical output to offset other deadly diseases associated with drink. Meanwhile, people who recently gave up alcohol could also reduce their chances of getting sick if they exercised more too.

Researchers from the University of Sydney used data from participants aged 30 years and over in ten British population-based health surveys. They then compared this with death rates of alcohol-related cancers which included oral cavity, throat, larynx, oesophagus, liver, colorectal, stomach and additionally pancreas and lung

Using models, they discovered a strong direct association between alcohol consumption and mortality risk of alcohol-related cancers, with a significantly higher risk among ex-drinkers.

They discovered people who drank excessive amounts of alcohol every week (more than 14 units for women and 21 for men) but who did at least seven hours of exercise were less likely to die from these cancers.

The study published in the International Study of Cancer last week added: “Engaging in a recommended level of physical activity attenuated the negative effects of alcohol consumption on alcohol-related cancer mortality.

“This provides valuable evidence of the potential of promoting physical activity as an adjunct risk minimisation measure for alcohol-related cancer prevention.”

It is the first time analysts have looked at the link between exercise and surviving cancers linked with alcohol. Anne McTiernan, a cancer prevention expert at the Fred Hutchinson Cancer Research Centre, said that the evidence between exercise and alcohol “was clear”.

Healthy diet may avert nutritional problems in head, neck cancer patients

Source: medicalxpress.com
Author: University of Illinois at Urbana-Champaign

At least 90 percent of head and neck cancer patients develop symptoms that affect their ability or desire to eat, because of either the tumor itself or the surgery or radiation used to treat it. These problems, called nutrition impact symptoms, have wide-ranging negative effects on patients’ physical and mental health and quality of life.

However, patients who eat foods high in antioxidants and other micronutrients prior to diagnosis may reduce their risks of developing chronic nutrition impact symptoms up to one year after being diagnosed with head or neck cancer, according to a recent study led by researchers at the University of Illinois.

The scientists analyzed the dietary patterns of 336 adults with newly diagnosed head and neck cancers and these patients’ problems with eating, swallowing and inflammation of the digestive tract. This painful inflammatory condition, called mucositis, is a common side effect of radiation treatment and chemotherapy.

The mitigating effects of a healthy diet were particularly significant in people who had never smoked and in patients who were underweight or normal weight at diagnosis, who often experience the greatest eating and digestive problems during treatment, said Sylvia L. Crowder, the paper’s first author.

Crowder is a research fellow in the Cancer Scholars for Translational and Applied Research program, a collaborative initiative of the U. of I. and Carle Foundation Hospital in Urbana, Illinois.

“While previous work has established that the presence of nutrition impact symptoms is associated with decreased food intake and weight loss, no studies have examined how pre-treatment dietary intake may influence the presence of these symptoms later in the course of the disease,” Crowder said.

In the early 2000s, researchers hypothesized that consuming antioxidant supplements might protect patients’ normal cells from damage during radiotherapy, enabling them to better tolerate treatment and higher dosages.

Accordingly, prior research by Anna E. Arthur, a professor of food science and human nutrition at the U. of I. and the current study’s corresponding author, indicated that eating a diet of whole foods abundant in antioxidants and phytochemicals improved recurrence and survival rates in head and neck cancer patients.

Like Arthur’s prior research, the new study was conducted with patients of the University of Michigan Head and Neck Specialized Program of Excellence.

Data on patients’ tumor sites, stages and treatment were obtained from their medical records. More than half of these patients had stage 4 tumors at diagnosis.

Prior to starting cancer treatment and again one year post-diagnosis, the patients completed a questionnaire on their diet, tobacco and alcohol use, and quality of life. Patients reported whether they experienced any of seven nutrition impact symptoms—such as pain or difficulty chewing, tasting or swallowing foods and liquids—and rated on a five-point scale how bothersome each symptom was.

In analyzing the patients’ eating habits, the scientists found that they followed either of two major dietary patterns—the Western pattern, which included high amounts of red and processed meats, fried foods and sugar; or the prudent pattern, which included healthier fare such as fruits and vegetables, fish and whole grains.

Patients who ate healthier at diagnosis reported fewer problems with chewing, swallowing and mucositis one year after treatment, the scientists found.

“While the origin and development of nutrition impact symptoms are complex and varied, they generally share one common mechanism—cell damage due to inflammation,” said Arthur, who is also an oncology dietitian with the Carle Cancer Center. “The prudent dietary pattern has the potential to reduce inflammation and affect the biological processes involved in the pathogenesis of these symptoms.”

The scientists hypothesized that some patients may begin eating healthier after being diagnosed with cancer, potentially counteracting the pro-inflammatory effects of their previous dietary habits.

Reverse causation was possible too, they hypothesized—patients’ lack of symptoms may have enabled them to consume a broader range of foods, including healthier whole foods, before their cancer was discovered.

January, 2020|Oral Cancer News|

Alcohol use high among cancer survivors

Source: www.medwirenews.com
Author: Shreeya Nanda

Over half of cancer survivors report being current drinkers, including about a fifth who appear to engage in excessive drinking behaviors, finds a US study.

“Given that alcohol intake has implications for cancer prevention and is a potentially modifiable risk factor for cancer-specific outcomes, the high prevalence of alcohol use among cancer survivors highlights the need for public health strategies aimed at the reduction of alcohol consumption,” write the study authors in JNCCN—Journal of the National Comprehensive Cancer Network.

They used data from 34,080 participants of the US National Health Interview Survey interviewed between 2000 and 2017 who reported a history of cancer.

In all, 56.5% of the total cohort reported being current drinkers, including 34.9% who exceeded moderate drinking limits – defined as a daily intake of more than one drink for women and more than two drinks for men – and 21.0% who engaged in binge drinking, which was defined as at least five drinks per day on at least one occasion in the past year.

Researcher Nina Sanford (University of Texas Southwestern Medical Center, Dallas, USA) and colleagues caution that for the blood alcohol concentration to reach the threshold for binge drinking, drinks generally need to be consumed within 2 hours, but the survey did not collect information on the duration of alcohol intake and therefore participants who reported binge drinking may not have reached the biologic threshold.

They also investigated factors linked to alcohol use, finding that younger age (18–34 years vs other age groups), current or former smoking status, and later survey period (2010–2014 and 2015–2017 vs 2000–2004) were significantly associated with a greater likelihood of current drinking, exceeding moderate drinking limits, and binge drinking.

For other factors, such as sex and ethnicity, associations were observed for some of the levels of current drinking but not all – for instance, female sex was significantly associated with exceeding moderate limits, but male sex was a significant predictor of reporting current drinking and binge drinking.

The prevalence rates and predictive factors were similar in sensitivity analyses that included just the 20,828 participants who had been diagnosed at least 5 years prior to survey administration.

“By reporting the demographic and socioeconomic variables associated with alcohol intake, our work begins to identify subgroups toward whom alcohol-based interventions could be targeted, and could serve as a benchmark for assessing changes in drinking behavior in the population of patients with cancer,” say Sanford et al.

Individuals with a history of cervical or testicular cancer were significantly more likely to report current drinking, exceeding moderate limits, and binge drinking compared with participants reporting other tumor types. Additionally, those with a history of head and neck cancer or melanoma were also significantly more likely to report binge drinking.

This finding is “likely a reflection of the predominant demographic characteristics—particularly younger age—associated with these cancer diagnoses, rather than an intrinsic association between cancer type and alcohol use,” comment the researchers.

Sanford and colleagues highlight the need for further research, “including large-scale systems-based research on alcohol use in cancer survivors.”

And they conclude: “For the time being, because oncologists have a responsibility to promote the overall health and well-being of their patients, efforts should be undertaken to accurately assess alcohol intake among cancer survivors and to inform these individuals of the potential harms associated with continued drinking.”

January, 2020|Oral Cancer News|

Test that looks at your spit to tell if you have mouth or throat cancer caused by HPV ‘could save thousands of lives if rolled out for doctors to use’

Source: www.dailymail.co.uk
Author: Connor Boyd, Health Reporter

A saliva test that diagnoses mouth and throat cancer caused by HPV could save thousands of lives each year, a study suggests. Scientists at Duke University in North Carolina discovered the test was 80 per cent accurate at spotting the killer diseases.

Doctors say it is able to detect the cancers early on, giving patients much higher hopes of surviving their battle. Before it can be used in hospitals around the world, further trials will be needed to confirm the technology works. But the researchers are hopeful, claiming the cheaper test – which gives results in as little as 10 minutes – has significant ‘potential’.

Rates of oral cancers are soaring in the Western world, with the number of patients diagnosed in the UK having doubled in a generation. US doctors have also seen a similar spike in the diseases, which can be caused by human papilloma virus (HPV).

The infection – spread through oral sex, as well as anal and vaginal intercourse – is thought to cause around 70 per cent of all cases. Other risk factors include drinking excessive amounts of alcohol over long periods of time and smoking cigarettes.

Professor Tony Jun Huang, study co-author, said there are around 115,000 cases of oropharyngeal cancers each year across the world. He said it is ‘one of the fastest-rising cancers in Western countries due to increasing HPV-related incidence, especially in younger patients’.

Orophayngeal cancer starts in the oropharynx, the back of the throat which includes the base of the tongue and tonsils. It sits under the branch of head and neck cancers, which also includes mouth cancer – another type that can be caused by HPV. Detecting the disease early can boost survival odds from 50 per cent to 90 per cent, according to the NHS. But patients are often not diagnosed until they become advanced, partly because their location makes them difficult to see during routine clinical exams.

The new test uses a chip developed to isolate tiny micro-particles, known as exosomes, in saliva.These particles are secreted into body fluids and several types of cancers are known to multiply their numbers. Exosomes are responsible for transferring molecules between cancer and various cells.

The new test isolates them by filtering out larger particles in the saliva and probing the exosomes for DNA shed by tumours. It also scans fluid in the mouth for HPV-16, one strain of the STI that can put people at risk of oropharyngeal cancer. The test takes five minutes to conduct and a further five to process the results. Experts also said it is cheap – but did not elaborate on the cost. In comparison, current biopsies take around eight hours because they need to be sent away to be assessed by a surgeon.

Professor Huang said: ‘It is paramount that surveillance methods are developed to improve early detection and outcomes.’ He added the successful detection of HPV from saliva ‘offers advantages including early detection, risk assessment, and screening’.

The test was a collaboration between Duke University, the University of California and University of Birmingham in Britain.

Orophayngeal cancer killed 2,722 Britons last year and took the lives of 9,750 people in the US, figures show. New cases of the disease in the UK have risen to 8,302 a year, a jump of 135 per cent compared with 20 years’ ago.

According to the researchers, this technology can also be used to analyse blood, urine, and plasma. The findings were published in the Journal of Molecular Diagnostics.

The Oral Health Foundation last month urged people to wise up to the causes of the ‘devastating’ disease, mainly HPV and alcohol. Dr Nigel Carter OBE, chief executive of the OHF, said: ‘While most cancers are on the decrease, cases of mouth cancer continue to rise at an alarming rate.

‘Traditional causes like smoking and drinking alcohol to excess are quickly being caught by emerging risk factors like the human papillomavirus (HPV).

‘We have seen first-hand the devastating affect mouth cancer can have on a person’s life.’

December, 2019|Oral Cancer News|

Research to examine possible links between periodontal disease and oral cancer

Source: eu.dental-tribune.com
Author: Dental Tribune International staff

As worldwide oral cancer rates continue to climb, our understanding of what causes the disease to occur, thankfully, also continues to grow. Tobacco use and excessive alcohol consumption have been established as primary risk factors, and researchers are now investigating another potential source for this condition: the bacteria that cause periodontal disease.

The research is being led by Dr Louise Belfield, a lecturer in biomedical science at the University of Plymouth’s Peninsula Dental School, in collaboration with the university’s Institute of Translational and Stratified Medicine. Since cancer requires blood vessels to grow and metastasise, the research team is planning to build on existing evidence that shows how certain bacteria that cause periodontal disease are linked to angiogenesis.

To do so, the research team will develop miniature tumours and blood vessels in a laboratory setting, adding the bacteria with the aim of clarifying how they function and what effect they have on the blood vessels.

According to a press release from the university, if the research ascertains that the bacteria make the blood vessels grow more rapidly and similarly to those associated with tumours and identifies the process by which this is achieved, the results could form the basis of a new screening programme to detect oral cancer risk earlier. This would make it possible to begin treatment in a more timely manner.

“We know that tumours in the mouth, unlike many other tumours, are in constant contact with bacteria, but we don’t know exactly how the bacteria affect tumour and vessel growth yet,” said Belfield.

“The bacteria may not cause the cancer, but they may do something to make the progression of the cancer speed up. One way they could do this is via the blood vessels, encouraging them to grow more rapidly or in a way which helps the tumour to grow. So if we find out what this is and how it works, it can help us develop and put screening processes in place to detect and reduce the numbers of those bacteria,” she continued.

Dental Tribune International (DTI) has previously reported on a study which confirmed the crucial role of dental professionals in detecting oral cancer early. This early detection can greatly improve the prognosis of sufferers.

“Oral cancer is a horrific disease with poor survival rates—only around 50% of those diagnosed are alive five years later. It is an in-your-face, no-hiding, disfiguring disease, and the treatment can be very protracted, complex and costly,” said Dr David Conway, Professor of Dental Public Health at the University of Glasgow’s School of Medicine, Dentistry and Nursing, in an interview with DTI last year.

“The earlier it is detected, however, the better the outcome can be,” Conway added.

November, 2019|Oral Cancer News|

Oral sex blamed for rise of mouth cancer in UK

Source: www.medicaldaily.com
Author: Darwin Malicdem

The number of people diagnosed with mouth cancer has significantly increased by 135 percent over the past 20 years in the United Kingdom. Experts believe the increase comes amid the growing number of Brits engaging in oral sex.

Nonprofit Oral Health Foundation (OHF) issued a report showing oral cancer rates “have more than doubled in a generation” across the U.K. In 2018 alone, seven people died every day from the disease in Great Britain and Northern Ireland.

“While most cancers are on the decrease, cases of mouth cancer continue to rise at an alarming rate,” Nigel Carter, chief executive of the OHF, told the Daily Mail. “It changes how somebody speaks, it makes eating and drinking more difficult, and often changes a person’s physical appearance.”

The foundation said the sexually transmitted human papillomavirus (HPV) caused 73 percent of the oropharyngeal mouth cancers. But drinking alcohol also contributed to the higher rates of the disease in the U.K.

OHF said 33 percent of mouth cancer diagnoses over the past decades were linked to consumption of alcoholic beverages. Smoking was associated with 17 percent of the cases.

The foundation launched Mouth Cancer Action Month in early November that aims to spread awareness of mouth cancer and its signs and symptoms.

“We want everyone to be more mouth aware during this year’s campaign,” Carter said in a press release. “This means being able to identify the signs and symptoms of mouth cancer, understand what is more likely to put us at greater risk, and importantly, know where to go if you spot anything out of the ordinary.”

He added early diagnosis has been effective to prevent deaths in the past years. Philip Lewis, of the Mouth Cancer Foundation, also highlighted that public awareness programs and self examination would help address the health issue.

In the U.S., the number of mouth cancer is also increasing. The Oral Cancer Foundation reported that nearly 54,000 Americans are being diagnosed with the disease every year.

Mouth cancer kills one person per hour in the country, leading to 13,500 deaths every year.

November, 2019|Oral Cancer News|

Say No to Glow: Reducing the Carcinogenic Effects of ALDH2 Deficiency

Source: blogs.plos.org
Author: Catherine Chang et al.

Turning red after consuming alcohol may seem like a mere social inconvenience. Yet, behind this red complexion lies a far more serious problem. ALDH2 deficiency, more commonly known as Alcohol Flushing Syndrome or Asian Glow, is a genetic condition that interferes with the metabolism of alcohol. As a result, people with ALDH2 deficiency have increased risks of developing esophageal and head and neck cancers . Globally, this deficiency affects 540 million people — 8% of the world population. In East Asia (which includes Japan, China, and Korea), this is a much bigger problem, where 36% of the population is affected [1]. In our home, Taiwan, approximately 47% of the population carries this genetic mutation — the highest percentage in the world [2]!

Normally, ethanol is first converted to acetaldehyde (a toxic intermediate) by the enzyme alcohol dehydrogenase (ADH). A second enzyme, aldehyde dehydrogenase 2 (ALDH2), then converts toxic acetaldehyde into acetate, a compound which can be safely metabolized in the body. For people who carry wild type ALDH2*1, acetaldehyde can be broken down quickly. People with ALDH2 deficiency, however, have a point mutation which leads to the less efficient mutant ALDH2*2 [3], [4]. Enzymatic activity in ALDH2-deficient individuals can be as low as 4% compared to wild type [4], [5], [6], [7]. As a result, acetaldehyde accumulates and induces an inflammatory response that causes the skin to flush after drinking alcohol [8]. Turning red is the most obvious result of ALDH2 deficiency, but symptoms also include headaches, dizziness, hypotension, and heart palpitations [5], [9].

Acetaldehyde accumulates in ALDH2-deficient individuals. Ethanol is first converted to a toxic intermediate, acetaldehyde, by ADH, then converted to acetate by wild type ALDH2*1. The mutant form, ALDH2*2, cannot fully convert acetaldehyde into acetate, and toxic acetaldehyde accumulates as a result.

For people who are ALDH2-deficient and drink, acetaldehyde can accumulate to toxic levels. The International Agency for Research on Cancer classifies acetaldehyde associated with alcohol consumption as a Group 1 carcinogen [10]. Acetaldehyde levels over 50 μM are considered toxic and cause mutations in DNA, and studies show that the strongest effects are seen in the mouth [11], [12]. After consuming roughly 2 to 3 servings of alcohol (0.5-0.6 g alcohol/kg body weight), salivary acetaldehyde levels in ALDH2-deficient individuals reached over 100 μM, compared to normal levels of <20 μM without drinking [13], [14], [15], [16]. Because of the increased salivary acetaldehyde, people with ALDH2 deficiency are 2 to 8 times more likely to develop head and neck cancers (including oral cancer, pharyngeal cancer, laryngeal cancer, etc.), and 2 to 12 times more likely to develop esophageal cancer compared to people with normal ALDH2*1 [17-25].

Our ALDH2*1 probiotic candy significantly reduces acetaldehyde levels in simulated oral conditions. (A) The conversion of acetaldehyde to acetate by ALDH2 uses NAD+ and produces NADH. (B) Experimental setup. The candies were dissolved, the probiotic (Nissle) was lysed to release ALDH2 enzymes, and the supernatant was placed into artificial saliva. NADH concentration was measured by taking absorbance readings at 340 nm. (C) Enzymatic activity of ALDH2*1 and ALDH2*2 from the probiotic candies. A negative control of candy without Nissle was also included (gray). Under these conditions, the ALDH2*1 candies metabolized significantly more acetaldehyde compared to both the ALDH2*2 candies and the negative control. Error bars represent standard error.

To directly address the increased esophageal and head and neck cancer risks, we developed a probiotic (E. coli Nissle 1917) candy carrying recombinant human ALDH2*1 to maintain normal acetaldehyde levels in the mouths of ALDH2-deficient individuals. We tested the candy’s ability to break down acetaldehyde by measuring NADH, a byproduct of acetaldehyde metabolism. In simulated oral conditions, we observed a significant decrease in acetaldehyde levels when we added the contents of our ALDH2*1 candy (compared to the mutant ALDH2*2 or control candy). Through mathematical modeling, we also determined the exact amount of recombinant ALDH2*1 needed in each piece of candy. Our modeling shows that if a consumer eats our candy while drinking, the released ALDH2*1 will be able to combat the high salivary acetaldehyde levels and match the normally low levels found in wild type individuals.

 

Our final product, an ALDH2*1 probiotic candy!

Nearly half of Taiwan’s population is ALDH2 deficient. To combat the increased cancer risks associated with this deficiency, we developed and tested a method to regulate acetaldehyde levels in ALDH2-deficient individuals.

The TAS_Taipei iGEM Team have produced a full research article detailing their project. You can access that article here.

Note:Please note that the team’s full research article has not been peer-reviewed.

Authors: Catherine Chang, Tim Ho, Iris Huang, Justin Wu

References:
1. Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A. (2009). The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption. PLoS Med. 24;6(3):e50.

2. Chang JS, Hsiao JR, Chen CH. (2017). ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective. J Biomed Sci. 24(1):19.

3. Larson HN, Weiner H, Hurley TD. (2005). Disruption of the Coenzyme Binding Site and Dimer Interface Revealed in the Crystal Structure of Mitochondrial Aldehyde Dehydrogenase “Asian” Variant. J Biol Chem. 280(34):30550-6.

4. Farrés J, Wang X, Takahashi K, Cunningham SJ, Wang TT, Weiner H. (1994). Effects of changing glutamate 487 to lysine in rat and human liver mitochondrial aldehyde dehydrogenase. A model to study human (Oriental type) class 2 aldehyde dehydrogenase. J Biol Chem. 13;269(19):13854-60.

5. Chen CH, Ferreira JCB, Gross ER, Mochly-Rosen D. (2014). Targeting Aldehyde Dehydrogenase 2: New Therapeutic Opportunities. Physiol Rev. 94(1):1-34.

6. Zhou J, Weiner H. (2000). Basis for half-of-the-site reactivity and the dominance of the K487 oriental subunit over the E487 subunit in heterotetrameric human liver mitochondrial aldehyde dehydrogenase. Biochemistry. 39(39):12019-24.

7. Gross ER, Zambelli VO, Small BA, Ferreira JCB, Chen CH, Mochly-Rosen D. (2015). A personalized medicine approach for Asian Americans with the aldehyde dehydrogenase 2*2 variant. Annu Rev Pharmacol Toxicol. 55:107-27.

8. Ijiri I. (1999). [Biological actions of acetaldehyde]. Nihon Hoigaku Zasshi. 53(3):285-95.

9. Lai CL, Yao CT, Chau GY, Yang LF, Kuo TY, Chiang CP, Yin SJ. (2014) Dominance of the inactive Asian variant over activity and protein contents of mitochondrial aldehyde dehydrogenase 2 in human liver. Alcohol Clin Exp Res. 2014 Jan;38(1):44-50.

10. International Agency for Research on Cancer. (n.d.). List of Classifications, Volumes 1-122. Retrieved from https://monographs.iarc.fr/list-of-classifications-volumes/ .

11. Yamaguchi H, Hosoya M, Shimoyama T, Takahashi S, Zhang JF, Tsutsumi E, Suzuki Y, Suwa Y, Nakayama T. (2012). Catalytic removal of acetaldehyde in saliva by a Gluconobacter strain. J Biosci Bioeng. 114(3):268-74.

12. Kocaelli H, Apaydin A, Aydil B, Ayhan M, Karadeniz A, Ozel S, Yilmaz E, Akgün B, Eren B. (2014) Evaluation of potential salivary acetaldehyde production from ethanol in oral cancer patients and healthy subjects. Hippokratia. 18(3): 269–274.

13. Homann N, Jousimies-Somer H, Jokelainen K, Heine R, Salaspuro M. (1997a). High acetaldehyde levels in saliva after ethanol consumption: methodological aspects and pathogenetic implications. Carcinogenesis. 18(9):1739-43.

14. Yokoyama A, Tsutsumi E, Imazeki H, Suwa Y, Nakamura C, Mizukami T, Yokoyama
(2008). Salivary acetaldehyde concentration according to alcoholic beverage consumed and aldehyde dehydrogenase-2 genotype. Alcohol Clin Exp Res. 32(9):1607-14.

15. Lachenmeier DW, Monakhova YB. (2011). Short-term salivary acetaldehyde increase due to direct exposure to alcoholic beverages as an additional cancer risk factor beyond ethanol metabolism. J Exp Clin Cancer Res. 30 (3).

16. Stornetta A, Guidolin V, Balbo S. (2018). Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity. Cancers (Basel). 10(1). pii: E20.

17. Chao YC, Wang LS, Hsieh TY, Chu CW, Chang FY, Chu HC. (2000). Chinese Alcoholic Patients with Esophageal Cancer are Genetically Different from Alcoholics with Acute Pancreatitis and Liver Cirrhosis. Am J Gastroenterol. 95(10):2958-2964.

18. Yang SJ, Wang HY, Li XQ, Du HZ, Zheng CJ, Chen HG, Mu XY, Yang CX. (2007). Genetic Polymorphisms of ADH2 and ALDH2 Associated with Esophageal Cancer Risk in Southwest China. World J Gastroenterol. 13(43):5760-5764.

19. Yokoyama A, Muramatsu T, Omori T, Yokoyama T, Matsushita S, Higuchi S, Maruyama K, Ishii H. (2001). Alcohol and Aldehyde Dehydrogenase Gene Polymorphisms and Oropharyngolaryngeal, Esophageal and Stomach Cancers in Japanese Alcoholics. Carcinogenesis. 22(3): 433-439.

20. Matsuo K, Hamajima N, Shinoda M, Hatooka S, Inoue M, Takezaki T, Tajima K. (2001). Gene-Environment Interaction between an Aldehyde Dehydrogenase-2 (ALDH2) Polymorphism and Alcohol Consumption for the Risk of Esophageal cancer. Carcinogenesis. 22(6): 913-916.

21. Cui R, Kamatani Y, Takahashi A, Usami M, Hosono N, Kawaguchi T, Tsunoda T, Kamatani N, Kubo M, Nakamura Y, Matsuda K. (2009). Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk. Gastroenterology. 2009 Nov;137(5):1768-75.

22. Lee CH, Lee JM, Wu DC, Goan YG, Chou SH, Wu IC, Kao EL, Chan TF, Huang MC, Chen PS, Lee CY, Huang CT, Huang HL, Hu CY, Hung YH, Wu MT. (2007). Carcinogenetic impact of ADH1B and ALDH2 genes on squamous cell carcinoma risk of the esophagus with regard to the consumption of alcohol, tobacco and betel quid. Int J Cancer. 122(6):1347-56.

23. Wu M, Chang SC, Kampman E, Yang J, Wang XS, Gu XP, Han RQ, Liu AM, Wallar G, Zhou JY, Kok FJ, Zhao JK, Zhang ZF. (2013). Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: a population-based case-control study in China. Int J Cancer. 132(8):1868-77.

24. Huang CC, Hsiao JR, Lee WT, Lee YC, Ou CY, Chang CC, Lu YC, Huang JS, Wong TY, Chen KC, Tsai ST, Fang SY, Wu JL, Wu YH, Hsueh WT, Yen CJ, Wu SY, Chang JY, Lin CL, Wang YH, Weng YL, Yang HC, Chen YS, Chang JS. (2017). Investigating the Association between Alcohol and Risk of Head and Neck Cancer in Taiwan. Sci Rep. 7(1):9701.

25. Hiraki A, Matsuo K, Wakai K, Suzuki T, Hasegawa Y, Tajima K. (2007). Gene–gene and gene–environment interactions between alcohol drinking habit and polymorphisms in alcohol-metabolizing enzyme genes and the risk of head and neck cancer in Japan. Cancer Science. 98: 1087-1091.

September, 2019|Oral Cancer News|

Twitter lends insight to HPV-associated oral cancer knowledge

Source: www.oncnursingnews.com
Author: Brielle Benyon

The incidence of human papillomavirus (HPV)-associated oral cancer has risen in recent years, and the virus has now surpassed tobacco and alcohol use as the leading cause of the disease. In fact, while the HPV vaccine is typically associated with preventing cervical cancer, there have been more cases of HPV-associated oral cancer than there have been cervical cancer.1

While the link between oral cancer and HPV may be well-known to healthcare professionals, researchers at Howard University recently took to Twitter to get a glimpse into the public’s knowledge about the topic.

“By looking at the social media data, we wanted to know what people are hearing about oral cancer – especially HPV-caused oral cancer,” study co-author Jae Eun Chung, PhD, associate professor in the Department of Strategic, Legal & Management Communication at Howard University, said. “We wanted to see what the gaps are between the knowledge of the healthcare professionals and the public.”

The researchers collected 3,229 unique tweets over the course of 40 weeks using search terms such as “HPV or papilloma” and “mouth or oral or throat or pharyngeal or oropharyngeal.” They then used a program called nVivo 12.0 to conduct a content analysis that looked at certain phrasing, terms, and themes that commonly appeared.

More than half (54%; 1679 total) of the tweets had information about prevention, while 29% (910) were about the causes of oral cancer. Far fewer tweets were about treatment (5%; 141), diagnosis (3%; 97), symptoms (1%; 42), and prognosis (1%; 25).

Interestingly, the researcher discovered a prominence on the risk of HPV-associated oral cancer in men, with tweets that referred to males outnumbering tweets that referred to females in a 3:1 ratio. Also, the most popular hashtag used in the dataset was #jabsfortheboys, appearing in 89 tweets.

“There was a heavy emphasis on the risk of HPV-associated (oropharyngeal cancer) among men, which is different than what we see with HPV vaccination among girls,” Chung said. “That was very positive news to us, because HPV-associated (oral cancer) rates are higher among the male population and HPV vaccination rates are higher among girls.”

While spreading HPV vaccination and oral cancer is important on a global scale, the United States might have some catching up to do, as the 5 most mentioned Twitter users discussing the topic were located outside of the US–1 in New Zealand, 2 in Australia, and 2 in the United Kingdom.

“That’s kind of sad, because there are more Twitter users from the United States than from any other country,” Chung said.

Ultimately, Chung explained, these findings outlined an area where the country can benefit from more education and social media campaigns.

“In conclusion, this study provides some insight as to how the public makes sense of HPV-associated oral cancer,” she said. “More education and campaigns are needed, and US residents can benefit from more active involvement of US-based health education.”

Reference
1. Chung JE, Mustapha I, Gu X, Li J. Understanding public perception about human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) through Twitter. Presented at: D.C. Health Communication Conference; Fairfax, Virginia; April 26-27, 2019.

‘Whitish patch’: increase in oral dysplasia in young adults

Source: www.medscape.com
Author: Kristin Jenkins

Most 8-year-olds with a wiggly tooth expect the Tooth Fairy to tuck some money under their pillow. In the case of one little Canadian boy, his wiggly tooth got him an incisional biopsy, a diagnosis of oral squamous cell carcinoma (OSCC), a partial maxillectomy, and a defect that was closed with local advancement flaps.

“This was the most unusual case we’ve seen,” said Marco A. Magalhaes, DDS, PhD, assistant professor of oral pathology and oral medicine in the Faculty of Dentistry at the University of Toronto in Ontario, Canada.

“OSCC predominantly affects patients 40 years of age and older,” write Magalhaes and colleagues in a case study report published in November 2016 in Oral Surgery Oral Medicine Oral Pathology Oral Radiology. “It is extremely rare in patients younger than 20 years of age.”

The clinical, radiographic, and histologic findings in this young patient were distinctive. Although the diagnosis and treatment were challenging, the clinical course was favorable at follow-up, the authors said. This case illustrates the fact that even pediatric patients can be at risk for OSCC. Magalhaes said that he and other dentists are concerned about the rising number of OSCC cases in patients who are in their 20s and 30s. These patients have no known risk factors and are often without symptoms. Many are diagnosed with high-grade oral epithelial dysplasia (OED) that rapidly progresses to cancer, Magalhaes told Medscape Medical News.

“When you look at the distribution of cases of oral dysplasia or carcinoma, you see that they tend to occur in older males in their 50s with a history of smoking and a low risk of [malignant] transformation,” he explained.

“What we are seeing in practice, however, is a lot of dysplasia in younger individuals without risk factors. These cases are the most concerning,” he commented.

At the time of presentation, patients may say, “I’m not sure why I’m here, but I saw a whitish patch in my mouth,’ ” said Magalhaes.

Others may be asymptomatic and have “absolutely no concerns,” he pointed out. “Unfortunately, this story is becoming more common.”

Nonhealing Sore in Mouth
Oral cancer usually presents as a nonhealing sore that is often painful. OED can be more difficult to diagnose because it manifests as a faint whitish or red patch anywhere in the oral cavity.

The gums, tongue, soft palate, and the inside of the cheeks can be affected. Most commonly, the floor of the mouth is affected.

Currently, Magalhaes and colleagues are conducting a review of more than 3000 cases of dysplasia in Ontario to determine group distribution, pattern, and, potentially, risk factors.

Although oral cancer has multiple causal factors, Magalhaes noted that smoking is “by far” the most significant and well-recognized risk factor. Heavy alcohol consumption is also a well-known risk factor. Human papillomavirus accounts for 5% to 6% of oral cancers, he noted.

A regular dental checkup is important, and early detection is critical for survival, Magalhaes emphasized.

For high-grade OED, the risk for progression to frank carcinoma is 18% to 30%, he noted. For moderate-grade OED, the risk is 10% to 15%, and for low-grade oral dysplasia, it is 1% to 4%.

“Physicians should reinforce to their patients the importance of dental checkups at least twice a year,” Magalhaes said. “This alone would increase the chances of early lesion detection.”

Review of Biopsy Specimens
A recent review of 63,483 biopsy specimens submitted by dentists to the Toronto Oral Pathology Service (TOPS) primarily from 2005 through 2015 bears this out. The review, led by Magalhaes, was published online April 25 in the Journal of the American Dental Association.

TOPS is operated by the Faculty of Dentistry at the University of Toronto and is one of the largest oral pathology services in Canada, noted Magalhaes, who works there.

The results show that generally, the incidence of OED (2679 cases) and OSCC (828 cases) in Ontario remained stable from 2005 to 2015. It also showed that when it comes to early detection of oral lesions, dentists have seriously stepped up their game. During the 10-year period, detection of OED by dentists increased 3.8-fold. The number of OSCC cases they detected doubled. OSCC accounted for about 10% of all oral cancers in the province in 2015.

“These biopsy specimens were submitted mostly by specialists in oral and maxillofacial surgery, periodontics, endodontics, and oral and maxillofacial pathology and oral medicine,” the authors write.

“However,” they continue, “informal discussion with clinicians who submitted the biopsy specimens has indicated that the initial detection of the mucosal abnormality was often accomplished by the general practice dentist, dental hygienist, or both, who referred the patient to specialists for evaluation, biopsy, and case management.”

The study also shows that potentially malignant lesions made up 4.68% of all cases and that OED accounted for 90%. An increased awareness of early lesions with malignant potential can result in early diagnosis and decreased morbidity and mortality from OSCC, the researchers say.

Both dentists and patients appear to be maintaining a high index of suspicion, according to Magalhaes.

“Dentists are increasingly aware of the presence of these early lesions and are either biopsying them themselves or sending them for biopsy,” he explained. “We’ve also noticed that patients are more aware of mouth changes and are asking dentists about lesions that they have identified.”

During a routine dental checkup, an examination for early signs of oral cancer is performed. This includes inspection of the lymph glands in the neck and a check of all mucosal surfaces in the oral cavity for signs of ulcers or red or white patches.

The severity of OED determines treatment, noted Magalhaes. In cases of low-grade OED, the lesion is monitored every 6 months, and a repeat biopsy is performed if warranted. A high-grade OED that is accessible and relatively well contained is treated with complete surgical excision. This is followed by monitoring two or three times a year. When the lesion is diffuse, affects 60% of the oral cavity, or extends into areas that are difficult to access without significant morbidity, the patient is closely monitored with examinations four times a year, he said.

Source:
J Am Dent Assoc. Published online April 25, 2019. Abstract

Oral Surg Oral Med Oral Pathol Oral Radiol. 2016 Nov;122:e179-e185. Full text