New study sheds light on why cancer often strikes those with healthy lifestyles.


Most cancer mutations are due to random DNA copying ‘mistakes,’ not inherited or environmental factors, Johns Hopkins researchers say

A new study by scientists at Johns Hopkins provides evidence that random, unpredictable DNA copying “mistakes” account for nearly two-thirds of the mutations that cause cancer.

The researchers say their conclusions are supported by epidemiologic studies showing that approximately 40 percent of cancers can be prevented by avoiding unhealthy environments and lifestyles. But among the factors driving the new study, they add, is that cancer often strikes people who follow all the rules of healthy living—nonsmoker, healthy diet, healthy weight, little or no exposure to known carcinogens—and have no family history of the disease, prompting the pained question, “Why me?”

ACROSS THE 32 CANCER TYPES STUDIED, THE RESEARCHERS ESTIMATE THAT 66 PERCENT OF CANCER MUTATIONS RESULT FROM COPYING ERRORS, 29 PERCENT CAN BE ATTRIBUTED TO LIFESTYLE OR ENVIRONMENTAL FACTORS, AND THE REMAINING 5 PERCENT ARE INHERITED.

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer. But it is not as well-known that each time a normal cell divides and copies its DNA to produce two new cells, it makes multiple mistakes,” says Cristian Tomasetti, assistant professor of biostatistics at the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins Bloomberg School of Public Health. “These copying mistakes are a potent source of cancer mutations that historically have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

Adds Bert Vogelstein, co-director of the Ludwig Center at the Kimmel Cancer Center: “We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations. However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed,”

Tomasetti and Vogelstein’s research will be published Friday in the journal Science.

Current and future efforts to reduce known environmental risk factors, they say, will have major impacts on cancer incidence in the U.S and abroad. But they say the new study confirms that too little scientific attention is given to early detection strategies that would address the large number of cancers caused by random DNA copying errors.

“These cancers will occur no matter how perfect the environment,” Vogelstein says.

In a previous study authored by Tomasetti and Vogelstein in the Jan. 2, 2015, issue of Science, the pair reported that DNA copying errors could explain why certain cancers in the U.S., such as those of the colon, occur more commonly than other cancers, such as brain cancer.

Cristian Tomasetti (left) and Bert Vogelstein

Image caption:Cristian Tomasetti (left) and Bert Vogelstein

In the new study, the researchers addressed a different question: What fraction of mutations in cancer are due to these DNA copying errors?

To answer this question, the scientists took a close look at the mutations that drive abnormal cell growth among 32 cancer types. They developed a new mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it generally takes two or more critical gene mutations for cancer to occur. In a person, these mutations can be due to random DNA copying errors, the environment, or inherited genes. Knowing this, Tomasetti and Vogelstein used their mathematical model to show, for example, that when critical mutations in pancreatic cancers are added together, 77 percent of them are due to random DNA copying errors, 18 percent to environmental factors (such as smoking), and the remaining 5 percent to heredity.

In other cancer types, such as those of the prostate, brain, or bone, more than 95 percent of the mutations are due to random copying errors.

Lung cancer, they note, presents a different picture: 65 percent of all the mutations are due to environmental factors, mostly smoking, and 35 percent are due to DNA copying errors. Inherited factors are not known to play a role in lung cancers.

Looking across all 32 cancer types studied, the researchers estimate that 66 percent of cancer mutations result from copying errors, 29 percent can be attributed to lifestyle or environmental factors, and the remaining 5 percent are inherited.

The scientists say their approach is akin to attempts to sort out why “typos” occur when typing a 20-volume book: being tired while typing, which represents environmental exposures; a stuck or missing key in the keyboard, which represent inherited factors; and other typographical errors that randomly occur, which represent DNA copying errors.

“You can reduce your chance of typographical errors by making sure you’re not drowsy while typing and that your keyboard isn’t missing some keys,” Vogelstein says. “But typos will still occur, because no one can type perfectly. Similarly, mutations will occur, no matter what your environment is, but you can take steps to minimize those mutations by limiting your exposure to hazardous substances and unhealthy lifestyles.”

Tomasetti and Vogelstein’s 2015 study created vigorous debate from scientists who argued that their previously published analysis did not include breast or prostate cancers, and it reflected only cancer incidence in the United States.

Tomasetti and Vogelstein now report a similar pattern worldwide, however, supporting their conclusions. They reasoned that the more cells divide, the higher the potential for so-called copying mistakes in the DNA of cells in an organ. They compared total numbers of stem cell divisions with cancer incidence data collected by the International Agency for Research on Canceron 423 registries of cancer patients from 68 countries other than the United States, representing 4.8 billion people, or more than half of the world’s population. This time, the researchers were also able to include data from breast and prostate cancers. They found a strong correlation between cancer incidence and normal cell divisions among 17 cancer types, regardless of the countries’ environment or stage of economic development.

Tomasetti says these random DNA copying errors will only get more important as societies face aging populations, prolonging the opportunity for our cells to make more and more DNA copying errors. And because these errors contribute to a large fraction of cancer, Vogelstein says that people with cancer who have avoided known risk factors should be comforted by their findings.

“It’s not your fault,” says Vogelstein. “Nothing you did or didn’t do was responsible for your illness.”

In addition to Tomasetti and Vogelstein, Lu Li, a doctoral student in Tomasetti’s laboratory in the Department of Biostatistics at the Johns Hopkins Bloomberg School of Public Health, also contributed to the research.

Watch the video discussion. URL:https://youtu.be/R4rxlRsNcs8

Source:http://hub.jhu.edu

Johns Hopkins Study Finds Psilocybin’s Ideal Dose For Long-Term Positive Effects


Groundbreaking research at Johns Hopkins University of Medicine has provided insight into the benefits of mediated doses of psilocyben, the active psychedelic compound found in “magic” mushrooms.

Though undeniable benefits are reported across the world from those that use mushrooms, there have also been many accounts of “bad trips,” or people having taken too much and experienced waking nightmares.  The researchers wanted to get to the bottom of this and so they began a study consisting of individuals between the ages of 29 and 62.  The team selected 18 of sound mind and body to undergo five sessions, each of which were eight hours in length and timed one month apart.  During four of the sessions, the volunteers would receive varying dosages of the psilocybin compound and a placebo at the remaining session to serve as a control.

In the study, participants were encouraged to lay down and wear head phones or eye masks to provide a comfortable environment.

No participants knew how much psilocyben they were ingesting.

Researchers noticed higher doses correlated with more positive effects and that at the highest dose, 30mg/70kg, 78 percent of the subjects reported having experienced on of the top five most spiritually significant events of their lives, though the reported moments of anxiety, fear, and stress increased by six times.

The second highest dose, 20 mg/70kg, resulted in only one of the volunteers reporting any negative experiences and all volunteers reporting positive experiences and the lowest dose used for the study, 5 mg/70 kg, demonstrated discernible and long-lasting positive effects on behavior, attitude and overall outlook. So much so that even friends and family members of the volunteers were able to notice the changes.

“We seem to have found levels of the substance and particular conditions for its use that give a high probability of a profound and beneficial experience, a low enough probability of psychological struggle, and very little risk of any actual harm,” says lead author Roland Griffiths, PhD.

A followup 14 months after the study showed that 94 percent of the subjects felt the experience was definitely within their top 5 most significant spiritual experiences.

These exciting studies at Johns Hopkins continue to unlocked the potential of psilocyben as a medicine that is helping people come to terms with death and other severe forms of stress, while allowing them a new awakening and spiritual perspective.

$1 Billion Lawsuit: Government Funded Studies Intentionally Infected People with STDs. Here’s the story


A class action lawsuit has been filed against Johns Hopkins University for performing unethical,government-sponsored studies on Guatemalan citizens in the 1940s and 1950s. Doctors from the hospital, the suit alleges, deliberately infected soldiersprisoners, orphans, and the mentally ill with STDs like syphilis and gonorrhea — without their consent — in order to test whether or not penicillin could cure them. Consent was only granted from authorities in Guatemala.

  The lawsuit involves almost 800 plaintiffs, including affected family members and spouses of the original victims. It is seeking nearly a billion dollars in damages and also names the Rockefeller Foundation as complicit,saying it helped “design, support, encourage and finance” the studies. Additionally, it alleges that pharmaceutical giant, Bristol-Myers Squibb, supplied the penicillin. The revelations came only because Susan Reverby, a professor at Wellesley University, uncovered the evidencein 2010.

The lawsuit claims the following methods were used to infect subjects:

“During the experiments the following occurred:

1. Prostitutes were infected with venereal disease and then provided for sex to subjects for intentional transmission of the disease;

2. Subjects were inoculated by injection of syphilis spirochaetes into the spinal fluid that bathes the brain and spinal cord, under the skin, and on mucous membranes;

3. An emulsion containing syphilis or gonorrhea was spread under the foreskin of the penis in male subjects;

4. The penis of male subjects was scraped and scarified and then coated with the emulsion containing syphilis or gonorrhea;

5. A woman from the psychiatric hospital was injected with syphilis, developed skin lesions and wasting, and then had gonorrheal pus from a male subject injected into both of her eyes and;

6. Children were subjected to blood studies to check for the presence of venereal disease.”

Another disturbing element of the STD studies is that the 696 original “participants” were not notified of what was being done to them. They were not told of the consequences of the studies, provided medical care, or told how to stop the spread of the diseases. Many did not receive what was considered sufficient treatment in those years (only 60 of the plaintiffs in the suit are original victims as most are now dead — many directly because of the diseases they received).

Correspondence between one of the lead researchers and another doctor revealed that the researchers knew what they were doing was unethical. TheGuardian cites the letter, explaining doctors knew

…that if it were discovered by ‘some goody organization’ that the program was testing people who were mentally ill it would ‘raise a lot of smoke.’ The manager continues: ‘I see no reason to say where the work was done and the type of volunteer.’

A 2012 lawsuit against the federal government, rooted in the Federal Tort Claims Act, was dismissed by a federal judge. The judge ruled the United States could not be charged for actions committed outside the country. Unsurprisingly, in the 1940s, leaders of the experiment chose Guatemala because they knew they would not be permitted to conduct the study domestically. One of them, John Cutler, was a U.S. health service physician who was later involved in the notorious Tuskegee syphilis experiments, where 600 black men were left untreated for decades to study the effects of the disease.

When the news of the Guatemalan experiments surfaced in 2010, then-Secretary of State Hillary Clinton and Health Secretary Kathleen Sebelius issued an apology for the government program (after a presidential bioethics commission ruled the studies constituted “unconscionable basic violations of ethics.”)

Their statement said,

The conduct exhibited during the study does not represent the values of the US, or our commitment to human dignity and great respect for the people of Guatemala.

(It ignored the inconvenient detail that in the same time period as the experiments, the CIA ousted a democratically elected leader in order to protect corporate agriculture, which doesn’t exactly imply respect or dignity for the people.)

Both Johns Hopkins and the Rockefeller Foundation are denying guilt, instead shifting it to the originators of the study — the legally-exonerated U.S. government. The Rockefeller Foundation said the plaintiffs were trying “improperly to assign ‘guilt by association’ in the absence of compensation from the United States federal government.”

A spokesperson for Johns Hopkins argued,

Johns Hopkins did not initiate, pay for, direct of conduct the study in Guatemala. No nonprofit university or hospital has ever been held liable for a study conducted by the US government.

The university has vowed to defend itself against the lawsuit.

Though the federal government refuses to compensate the victims, its admission that the studies constituted egregious violations of ethics is telling.

As Marta Orellana, a victim who was nine years old when she was infected, said:

They never told me what they were doing, never gave me a chance to say no…I’ve lived almost my whole life without knowing the truth. May God forgive them.

 

NEW ORGANIC CARBON SPECIES LINKED TO FORMATION OF DIAMONDS AND LIFE ITSELF


Posted on 2014/11/25

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New findings by a Johns Hopkins University-led team reveal long unknown details about carbon deep beneath the Earth’s surface and suggest ways this subterranean carbon might have influenced the history of life on the planet.

The team also developed a new, related theory about how diamonds form in the Earth’s mantle.

For decades scientists had little understanding of how carbon behaved deep below the Earth’s surface even as they learned more and more about the element’s vital role at the planet’s crust. Using a model created by Johns Hopkins geochemistDimitri Sverjensky, Sverjensky, Vincenzo Stagno of the Carnegie Institution of Washington and Fang Huang, a Johns Hopkins graduate student, became the first to calculate how much carbon and what types of carbon exist in fluids at 100 miles below the Earth’s surface at temperatures up to 2,100 degrees F.

In an article published this week in the journal Nature Geoscience, Sverjensky and his team demonstrate that in addition to the carbon dioxide and methane already documented deep in subduction zones, there exists a rich variety of organic carbon species that could spark the formation of diamonds and perhaps even become food for microbial life.

“It is a very exciting possibility that these deep fluids might transport building blocks for life into the shallow Earth,” said Sverjensky, a professor in the Department of Earth and Planetary Sciences. “This may be a key to the origin of life itself.”

Sverjensky’s theoretical model, called the Deep Earth Water model, allowed the team to determine the chemical makeup of fluids in the Earth’s mantle, expelled from descending tectonic plates. Some of the fluids, those in equilibrium with mantle peridotite minerals, contained the expected carbon dioxide and methane. But others, those in equilibrium with diamonds and eclogitic minerals, contained dissolved organic carbon species including a vinegar-like acetic acid.

These high concentrations of dissolved carbon species, previously unknown at great depth in the Earth, suggest they are helping to ferry large amounts of carbon from the subduction zone into the overlying mantle wedge where they are likely to alter the mantle and affect the cycling of elements back into the Earth’s atmosphere.

The team also suggested that these mantle fluids with dissolved organic carbon species could be creating diamonds in a previously unknown way. Scientists have long believed diamond formation resulted through chemical reactions starting with either carbon dioxide or methane. The organic species offer a range of different starting materials, and an entirely new take on the creation of the gemstones.

The research is part of a 10-year global project to further understanding of carbon on Earth called the Deep Carbon Observatory. The work is funded by the Alfred P. Sloan Foundation.

 

Scientists at Johns Hopkins Come Closer to Eliminating Heart Disease .


A world without heart disease seems impossible. But researchers at Johns Hopkins just got one step closer.
Scientists at Johns Hopkins University may be one step closer to eradicating debilitating heart diseases in humans, particularly those caused by excessive buildup of cholesterol.

 

A new study published in the journal Circulation shows that a synthesized drug reduces, and may even eradicate, the effects of high-fat and high-cholesterol diets. And though the drug is prosperous for the heart and brain most specifically, the entire body may benefit from this development.

“It’s the entire cardiovascular system that’s affected,” Ekaterina Pesheva, a representative for Johns Hopkins, told The Daily Beast.The reason we’re worried about the heart and the brain is because those are the centers that end up being the most debilitating to human life when affected by fatty buildups.”

The study shows that the new drug under examination, known now as D-PDMP, changes the way fat metabolism works, and eliminates the risk of heart attack and heart disease. The drug halts the development of atherosclerosis, a word referring to the hardening of the arteries. Atherosclerosis is based on a buildup of fat and cholesterol in blood vessels, and happens to be the main cause of heart attacks in humans. Most notably, atherosclerosis is the No. 1 cause of death in humans (perhaps a little-known fact in a world rampant with famine, war, and crime).

Atherosclerotic heart disease is the most common type of heart disease, which develops when fat builds inside the blood vessels over time, rendering them stiff, narrowed, and hardened. This, in turn, reduces blood flow to the heart and brain.

Other kinds of heart disease include structural heart disease—people born with malformations of their heart, which is rare, and heart failure (mostly a result of poorly functioning heart muscle, which can be due to a number of causes, including atherosclerosis. It can also be caused by other conditions such as viral infections of the heart) will also benefit from this development.

Perhaps the most remarkable aspect of these new developments is that the compound used to control the atherosclerosis is a widely available, man-made compound.

Dr. Subroto Chatterjee, Ph.D, a cardio-metabolic expert at Johns Hopkins Medicine, spearheaded the research and development of this project. “Atherosclerotic, in most colloquial terms, means clogged vessels, or vessels thickened by buildup of fat inside the vessel,” Chatterjee told The Daily Beast. “And this research was quite challenging,” he said, “but we feel like we got quite lucky with the development here.”

Chatterjee and his team found that D-PDMP almost totally eliminated the buildup of cholesterol in vital regions of the body. Perhaps the most remarkable aspect of these new developments is that the compound used to control the atherosclerosis is a widely available, man-made compound.

The researchers tested the drug in mice and rabbits, Chatterjee told The Daily Beast. The mice were known to already have heart problems and the rabbits were known to have healthy hearts. That complicates the study, if only because the control group of the species isn’t specific to one cardiovascular system. Researchers fed both species a high-fat and high-cholesterol diet.

“Indeed, this diet nearly guarantees arteriosclerosis in these transgenic/mutant mice as they fail to handle LDL [low-density liver] cholesterol,” Chatterjee said. “In these animals on this diet, the risk of this disease is nearly 100%. There is one chance in four that your child may have blood cholesterol that is too high. Healthy individuals have a one in two chance of abnormally elevated blood cholesterol,” he said. “More than 70 million Americans have high cholesterol, according to the CDC.”

Cholesterol control is a contentious field in medical research, because the side effects of drugs used to treat the issue can be dangerous. The Daily Beast spoke with John McEvoy, a cardiology fellow in preventive cardiology physician, at Johns Hopkins, who was not involved with this particular study.

“It’s always very important when a new mechanism for treating high cholesterol and heart disease comes about,” McEvoy said. “This pathway and new treatment are very exciting in that regard. However, the next step for these researchers will be making sure there are no side effects of the drug that are harmful to humans.”

Chatterjee said that the actual development of the drug is about five years away. He put its science in simple terms

“Imagine you have clogged up plumbing due to debris,” Chatterjee said. “Similar clogging in our blood vessels occurs due to fat and cholesterol building up over time. Our drug, we hope, will prevent [or] delay the rise in cholesterol and fat and thus prevent thickening/hardening of the blood vessel. This is like the use of Drano to clean up our plumbing at home.”

Model Predicts Survival in Intrahepatic Cholangiocarcinoma.


A statistical model, or nomogram, has been developed to predict long-term survival of patients following resection for intrahepatic cholangiocarcinoma (ICC), based on data from an international multicenter study.

Although the tool is still investigational, the developers report that patients in the top quartile of predicted survival had a median survival of 80.2 months, compared with 14.8 months for those in the lowest quartile (P = .01).

The authors identified 6 variables that were the most closely associated with survival.

The findings were published online March 5 in JAMA Surgery by Omar Hyder, MD, from Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues.

Intrahepatic cholangiocarcinoma is the second most common primary liver malignant tumor, after hepatocellular carcinoma (HCC), and represents 10% to 20% of all primary liver malignant tumors, or about 3100 new cases every year in the US.

Yet the disease was only recently recognized as an entity distinct from HCC and provided its own unique staging system in the 7th edition of the American Joint Committee on Cancer (AJCC) Staging Manual. The previous 6 editions failed to make that distinction, said study coauthor Timothy M. Pawlik, MD, MPH, PhD, Director of the Johns Hopkins Medicine Liver Tumor Center Multi-Disciplinary Clinic, Johns Hopkins Hospital, told Medscape Medical News.

Although tumor staging is helpful, disease-specific nomograms also take into account clinical factors beyond pathology. “The nomogram will provide clinicians with a patient-specific way to predict survival following resection of ICC,” said Dr. Pawlik, who is also the John L. Cameron MD Professor of Alimentary Tract Diseases at Johns Hopkins.

Asked to comment on the study, David A. Geller, MD, Director of the UPMC Liver Cancer Center, University of Pittsburgh, in Pennsylvania, told Medscape Medical News, “developing a nomogram to predict survival after liver resection is very important,” noting that ICC incidence is increasing and overall prognosis is poor.

The majority of patients are inoperable at diagnosis, and in those who are able to undergo hepatic resection — the only chance for cure — overall 5-year survival is only 25% to 35%, added Dr. Geller, who was not involved in the study and is also the Richard L. Simmons Professor of Surgery at UPMC.

According to Dr. Geller, “This is a well-done multi-center, international study from leading centers around the world.” Once validated in external cohorts, “[the nomogram] potentially could be used to counsel patients and families about risk of recurrence, and could be one of several factors used by medical oncologists to discuss risks/benefits of adjuvant therapies.”

Dr. Pawlik said that the tool can be employed now. “Although the nomogram can be used now to help shape the discussion around patient prognosis, future validation should be performed.”

Six Variables Used to Predict Survival

Hyder and colleagues used data from a study of 514 patients who underwent resection for ICC at 13 major hepatobiliary centers in the United States, Europe, and Asia from 1990 through 2011. Approximately half (53%) of the patients were male and nearly two thirds (61%) were white. They had a mean age of 59 years.

Extended hepatectomy was performed in 39%, hemihepatectomy in 35%, and minor live resection in 26%. Median tumor size was 6.0 cm, with 56% having tumors of 5 cm or larger. Most of the patients (88%) had R0 surgical margins. Lymphadenectomy was performed in 49%, and 24% received adjuvant therapy.

Mean survival postsurgery was 39 months, with survival rates at 1, 3, and 5 years of 81%, 52%, and 40%, respectively.

From an initially selected 15 clinically relevant candidate variables, the authors identified 6 that were the most closely associated with survival. Of the 6 variables, 5 had statistically significant associations with P values < .05: age (hazard ratio [HR], 1.31); presence of multiple tumors (HR, 1.58); tumor size (HR, 1.50); lymph node metastasis (HR, 1.78); and macroscopic vascular invasion (HR, 2.1). The other variable, the presence of cirrhosis, carried a P value of .08 (HR, 1.51).

Further statistical examination of the effect of the 2 continuous variables — age and tumor size — revealed that both had a nonlinear effect on the risk for mortality. Specifically, the effect of tumor size was linear below a threshold of 7 cm, but was constant above that. Similarly, the highest risk for mortality was seen at extremes of age in both directions.

Based on the 6 variables, a nomogram was constructed with points assigned to indicate a survival prognosis. For example, lymph node metastasis was associated with 11 points, while the presence of macroscopic vascular invasion was given 15 points. Higher scores indicate worse prognosis.

The nomogram has a 69% probability of accurately predicting survival, say the study authors, referring to a calculation of the “Harrell’s C-index.”

In comparison, the probable accuracy for predicting survival in all cancer with the 7th edition of the AJCC Cancer Staging Manual is just 59%. For the 6th edition, which had staged ICC the same as HCC, the prognostic ability for ICC was 54%, the authors note.

Role of Tumor Size Reassessed

Dr. Pawlik told Medscape Medical News that his group had previously published findings showing no effect on tumor size. As a result, that variable is not included in the current AJCC ICC staging system.

The reason for the discrepancy with the current data may relate to the nonlinearity of the relationship between tumor size and prognosis, whereby it ceases to be significant above an approximate 7-cm diameter threshold. Previous studies may not have included enough patients with smaller tumors to have influenced the findings, the authors point out in their discussion.

This means that the AJCC staging will likely need to be revised to take tumor size into account as a predictor of survival, Dr. Pawlik told Medscape Medical News.

“Since the ICC staging in the current AJCC manual is the first version ever to be published, future refinements are to be expected. The nomogram is an important next step,” he said.

The authors point out that 1previous nomogram for ICC has been published, but it was based on data from just 1 center in China and evaluated age and tumor size as strictly linear variables.

Hopes Raised for Early Pancreatic Cancer Detection.


Scientists at the Johns Hopkins University School of Medicine say a simple blood test based on detection of tiny epigenetic alterations may reveal the earliest signs of pancreatic cancer. The findings of their research, if confirmed, they add, could be an important step in reducing mortality from the cancer, which has an overall five-year survival rate of less than 5% and has seen few improvements in survival over the last three decades.

“While far from perfect, we think we have found an early detection marker for pancreatic cancer that may allow us to locate and attack the disease at a much earlier stage than we usually do,” explains Nita Ahuja, M.D., an associate professor of surgery, oncology and urology at the Johns Hopkins and leader of the study (“Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer”) described online this month in the journal Clinical Cancer Research.

For their study, Dr. Ahuja and her colleagues focused on two genes.

“We used a nanoparticle-enabled MOB (Methylation On Beads) technology to detect early-stage pancreatic cancers by analyzing DNA methylation in patient serum,” wrote the investigators in their journal article. “We identified two novel genes, BNC1 (92%) and ADAMTS1 (68%), that showed a high frequency of methylation in pancreas cancers (n=143), up to 100% in PanIN-3 and 97% in Stage I invasive cancers.”

Together, BNC1 and ADAMTS1 were detectable in 81% of blood samples from 42 people with early-stage pancreatic cancer, but not in patients without the disease or in patients with a history of pancreatitis, a risk factor for pancreatic cancer.

Dr. Ahuja’s team found that, in pancreatic cancer cells, it appears that chemical alterations to BNC1 and ADAMTS1, i.e., epigenetic modifications that alter the way the genes function without changing the underlying DNA sequence, silence the genes and prevent them from making their protein product, the role of which is not well understood. These alterations are caused by the addition of a methyl group to the DNA.

Using MOB, the researchers were able to single out in the blood even the smallest strands of DNA of those two genes with their added methyl groups. The technique uses nanoparticle magnets to latch on to the few molecules being shed by the tumors, which are enough to signal the presence of pancreatic cancer in the body, the researchers found.

Dr. Ahuja says the practical value of any blood test for cancer markers depends critically on its sensitivity (meaning the proportion of tumors it detects) and its specificity (meaning how many of the positive results are false alarms). The specificity of this new pair of markers is 85%, meaning 15% would be false alarms. She hopes further research will help refine the test, possibly by adding another gene or two, in order to go over 90% in both sensitivity and specificity.