Biology of Childhood Leukemia

[vc_row][vc_column][vc_column_text css=”.vc_custom_1547064372616{margin-bottom: 0px !important;}”]by Julia Vassey[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547488146132{margin-bottom: 0px !important;}”]Joe Wiemels, a molecular epidemiologist at the UC Berkeley Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE) has spent 30 years deciphering the complex biology of childhood leukemia – the most prevalent cancer in children.

Leading leukemia scientists, including CIRCLE researchers, have used observational studies to draw links between the disease and unhealthy lifestyles, aberrant immune development, genetic risk factors, and exposure to environmental chemicals. But the biological mechanisms underpinning childhood leukemia remain unclear.

Wiemels is on a quest to find harder evidence – drilling down to the molecular level to understand how these risk factors can alter the way our genes work and, ultimately, cause cancer.

He has been investigating the role of genetics in childhood leukemia since the 1990s, when he started his postdoctoral program at the University of London’s Institute of Cancer Research. There, he worked with his mentor Mel Greaves, a well-known cancer cell biologist and childhood leukemia researcher.

The two scientists and their colleagues were thinking about cancer non-stop – in the labs at work and after hours, too, even in the local pubs, where they found loads of punters drowning in beer, fish-n-chips, and cigarettes.

“Eating well is good for you! Smoking is bad for you!” Wiemels mimicked. “People get tired of hearing these headlines.”

He came to believe that what people want is to have more tangible proof that these habits can really affect their health, “something that is specific, something that they can hold on to, meaningful for me,”  Wiemels says.

“Living in London was great fun and fruitful for research,” Wiemels says. His work there helped define the earliest genetic changes in a child’s life that lead to a leukemia diagnosis years later – these mutations occurred even before the child was born.

In the early 2000s, Wiemels moved to Northern California to start his own research lab, working alongside the UC Berkeley California Childhood Leukemia Study at CIRCLE and the Department of Epidemiology at the University of California, San Francisco.

In search of indisputable evidence of what causes cancer, Wiemels jumped headlong into the innovative science of epigenetics – the study of cellular modifications to DNA or, literally, what’s “on top of” genetics.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column][mk_fancy_title font_family=”none”]

Epigenetics and Leukemia Risk

[/mk_fancy_title][vc_column_text css=”.vc_custom_1546995559799{margin-bottom: 0px !important;}”]Epigenetic changes do not alter the genetic code itself, but they affect the way genes behave in our bodies: deciding what proteins are produced and what cells and tissues are formed.

Epigenetics can be as influential as a great director on a movie set. Two identical actors may be reading from the same script, but the director’s notes on blocking, cadence, and emotion can change the whole scene. Similarly, two cells with the same DNA code can have vastly different manifestations, depending on the epigenetic modifications present.

Epigenetics can also help explain why people have certain physical or physiological differences like the color of the skin, sleep patterns or even food preferences.

Epigenetic modifications also affect our bodies’ interaction with the environment, nutrition and exercise or infections every single minute of our lives – from conception to death.

“Epigenetics is everywhere,” says Wiemels, looking at the sunlight coming through the window in his office. “Right here! This light is inducing epigenetic changes in my eyes and skin.”[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][vc_column_text css=”.vc_custom_1546996374394{margin-bottom: 0px !important;}”]Wiemels is focusing on a specific epigenetic mechanism called methylation, which adds methyl groups – consisting of a carbon atom and three hydrogens (CH3) – to certain parts of a DNA molecule. Methylation can turn our genes on or off, making them active or dormant.

“If you are a liver, you don’t want to be a bone.” That was Wiemels pithy explanation.

In other words, each cell in our body has a specific purpose – one that is dictated by DNA methylation. Early in its life, each liver cell must “turn off” the genes that would have it making proteins to form bones. Likewise, each bone cell would amplify those genes and silence the ones that define a liver cell.

But in certain diseases like cancer, genes get switched away from a healthy state.[/vc_column_text][/vc_column][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/epigen_noshadow-1024×911-1.png” image_size=”large”][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547060324971{margin-bottom: 0px !important;}”]Childhood leukemia stems from a malfunction of white blood cells – B cells, which patrol the body like watchmen looking for intruding viruses and bacteria that would otherwise weaken the immune system.

When leukemia strikes, it’s because the bone marrow is producing unhealthy, immature B cells, which have too many or too few methyl groups attached to their DNA, along with certain genetic mutations in the DNA. This abnormal DNA methylation throws the immune system into disarray.

Wiemels showed that children diagnosed with leukemia had abnormal DNA methylation across about 10 percent of the genome in their white B cells. That’s a lot!

Wiemels believes many of these drastic epigenetic changes can be linked to our adaptations to environmental factors, like maternal cigarette smoking during pregnancy, or responding to infectious exposures.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column][mk_fancy_title font_family=”none”]

The Smoking Gun

[/mk_fancy_title][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547062665682{margin-bottom: 0px !important;}”]Smoking has already been shown to exert a strong effect on DNA methylation, even more so than other environmental chemicals CIRCLE is investigating, according to Wiemels.

[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/deletion-1.png” image_size=”full”][/vc_column][vc_column width=”1/2″][vc_column_text css=”.vc_custom_1547062931206{margin-bottom: 0px !important;}”]Wiemels and his colleague Adam de Smith, a researcher at the University of Southern California, Los Angeles, discovered that leukemia patients whose mothers smoked during pregnancy had tumors with more gene deletions – a chunk of DNA that is missing from a chromosome.

For each additional five cigarettes smoked daily during pregnancy, there was a 22 percent increase in the number of deletions; and for each additional five cigarettes smoked daily during breastfeeding, there was a 74 percent increase in the number of deletions.

While the results of previous research aimed to find the association between maternal smoking and the risk of leukemia were inconsistent, this was the first study to link maternal smoking with a specific mutation in childhood leukemia.

“This finding provides a rare glimpse at a causal factor, smoking, that creates a specific, definable wound in DNA. It’s like looking at a gunshot bullet hole,” Wiemels says.

[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547764942915{margin-bottom: 0px !important;}”]The deletions have also been blamed on triggering a gene re-arrangement mechanism called “recombinase activating gene”  – an exchange of genetic material within chromosomes. While this process is common and occurs naturally in lymphocytes (B and T cells), it can become detrimental for health, if stimulated by environmental chemicals like smoking.

By looking at epigenetic changes within smoking-sensitive regions of the DNA as well as the recombinase activating gene-associated deletions, Wiemels hopes to pinpoint how exactly tobacco caused the mutations.

To achieve his vision, Wiemels with other researchers from CIRCLE and the University of Southern California Center for Genetic Epidemiology that he has recently joined, will examine blood samples collected from 8,000 children, half of whom have been diagnosed with leukemia. The experiment is part of a new project funded by California’s Tobacco-Related Disease Research Program. Wiemels’ laboratory will use an innovative biomarker to determine which children were exposed to tobacco in utero.

“We will examine neonatal blood that provides the history of maternal smoking during pregnancy. We would be able to say if smoking was occurring and whether it was a little or a lot using this sensitive biological marker,” says Wiemels.

The researchers want to understand why some children who were exposed to tobacco in utero end up getting leukemia while others do not.

“The result from this analysis will directly address cancer prevention and help identify those individuals who would be especially susceptible to tobacco exposure,” Wiemels says.

In the future, Wiemels plans to investigate tobacco-caused epigenetic changes in sperm of the fathers who smoke, to follow-up on CIRCLE’s earlier findings that showed a link between paternal preconception smoking and the risk for childhood leukemia.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column][mk_fancy_title font_family=”none”]

CMV, the Silent Killer

[/mk_fancy_title][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547063836614{margin-bottom: 0px !important;}”]The role of infections in childhood leukemia is another area of Wiemels’ research.

In the 1980s and later on, his U.K mentor Greaves made a series of discoveries showing that mild infections early in life – the ones that children often catch at daycare centers – help build the immune system and reduce the risk of leukemia.

Wiemels is focusing on cytomegalovirus or “CMV” – a common virus to which many people are exposed (often without knowing it). CMV can remain dormant in a healthy human body for person’s whole lifetime, but can bloom into a fulminant infection among individuals whose immune systems are weakened or compromised, for example, by HIV or after organ transplantation. Wiemels hypothesizes that the virus can become dangerous only when a mother passes it to a child while still in the womb, subsequently increasing the risk of leukemia.

Previous CIRCLE studies found that children who developed leukemia were about three times more likely to have had the CMV virus at birth compared to healthy control children who did not get the cancer at that age. This may be a particular big problem for Latino children, who are more likely to be diagnosed with leukemia than other groups.

“The frequency of passing CMV from a mom to a child prenatally is a little bit higher in Hispanics, which may partially explain the higher risk of leukemia observed within this group – something we want to follow up on,” Wiemels says.

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Folate Helps

[/mk_fancy_title][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][vc_column_text css=”.vc_custom_1547064078862{margin-bottom: 0px !important;}”]Early pregnancy is a critical moment for epigenetic programming. It’s “when the most DNA methylation patterns are set up all over the body for every single tissue,” Wiemels explains.

As such, factors that impact DNA methylation during pregnancy can be strong risk factors for childhood leukemia.

Folate is the main shuttle that carries methyl groups around the body during cellular development, delivering them to specific DNA sites that needs to be methylated.

If a child growing inside the mother’s womb doesn’t get enough folate, it may lead to unhealthy epigenetic changes.[/vc_column_text][/vc_column][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/4-25-18-folate-infographic-5-5×8-5.png” image_size=”full” desc=”Infographic by CIRCLE” caption_location=”outside-image”][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547064088488{margin-bottom: 0px !important;}”]These alterations can be carried on to birth and early childhood to manifest as a leukemia around the age of two or three, when kids most contract the disease. Wiemels and his colleagues have observed such changes in children who received less folate from their mothers in early pregnancy, compared to mothers with better nutrition, and are working to understand how these changes may affect leukemia risk.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column][mk_fancy_title font_family=”none”]

What’s Next

[/mk_fancy_title][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547064240290{margin-bottom: 0px !important;}”]Wiemels is committed to his quest for hard evidence of what causes childhood leukemia, but he admits that epigenetics is quite challenging to study.

He calls it “a moving target,” because of the constant changes that occur in a cell’s composition during the first weeks of a child’s life. For example, the number of erythrocytes – the red blood cells – naturally decline in an infant’s body soon after birth. Because each type of blood cell has a unique level of DNA methylation, as the blood’s composition changes, so too does the DNA methylation that Wiemels and his team measures.

“How do you control for all these factors and still get meaningful results in the end for the individual?  Wiemels says. “A lot of epidemiologists may point fingers at me saying that you’ll never going to prove anything.”

But Wiemels hopes epigenetic discoveries will eventually “become the lexicon of cancer prevention,” Wiemels says.

On a recent visit to his old laboratory in London, Dr. Wiemels had this discussion with his former mentor.

“Greaves is 77, but he is still energetic and full of command,” Wiemels says. Greaves hopes to make new discoveries in childhood leukemia research by taking a closer look at a microbiome – a vast army of microbes that protects infants in the wombs and soon after birth from harmful infections that can trigger cancer.

Wiemels believes the recipe for success in fighting leukemia is to gather all possible data at different stages of a child and his parents’ lives, learning about the child’s birth, genes, and exposures to infections and chemicals like pesticides.

It is also important to look at all the factors in combination, instead of analyzing it one a time. Powerful statistical tools and DNA sequencing methods that have recently emerged allow to study “hundreds and thousands to millions of data points,” Wiemels says.

“Following these steps, I hope we are going to see that there are impacts of pesticides on some children that may not be evident for other children. Or we may discover that kids have different susceptibility to infections. This will show us a clear causal route to leukemia for each person with the disease and point towards early detection and prevention,” he says.

Comparing different types of cancers may also bring new insights. In his new researcher position at the University of Southern California Center for Genetic Epidemiology, Wiemels is focused on brain tumors’ origin and prevention, while continuing investigating the causes of leukemia at CIRCLE.

Wiemels will examine pediatric glioma brain tumors with a similar type of analysis that was done by the CIRCLE researchers when they looked at the environmental risk factors for leukemia.

All childhood cancers, including glioma and leukemia, are similar.  Compared to adult cancers, they are genetically simple, they develop quickly and occur in tissues that are rapidly emerging and growing, making children particularly susceptible to outside disruptions –  from chemicals, diet or infections.

But despite these similarities, each child has their own pathway to cancer, – and that is researchers’ greatest challenge to prevention, according to Wiemels.

“In this era of ‘personalized medicine’ we must also imagine ‘personalized prevention’ and create a society, in which each of us with our differences can thrive,” Wiemels says.

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Chasing the Dust

[vc_row][vc_column][vc_column_text css=”.vc_custom_1653018570420{margin-bottom: 0px !important;}”]by Julia Vassey

 

Wearing an aerosol mask and rubber gloves, Todd Whitehead, a researcher at the University California, Berkeley, was sifting through dust, prepping it for chemical analysis.

Dozens of vacuum bags stashed on the lab table came from all across California. People who participated in the California Childhood Leukemia Study were asked to vacuum floors in their homes and send that sucked-in dust to the UC Berkley School of Public Health to get it tested for the presence of toxic chemicals.[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][vc_column_text css=”.vc_custom_1546985075213{margin-bottom: 0px !important;}”]Dust seems really innocuous, “just something you have to deal with” from time to time cleaning your home or office, but it is actually a “hazardous material” says Whitehead.

Contaminated dust is a source of environmental pollution just the same as dirty air, water, or food can be.

The researcher likes to think of dust as “a puzzle” – a complex mixture of tiny particles from different places, each one with multiple chemicals stuck to it.

The dust samples are just a messy knot of hair, lint, and breakfast cereal – the typical contents of any used vacuum cleaner bag. To deconstruct the puzzle, you need to untangle these knots, “look at individual dust particles and try to pinpoint the sources of chemical contamination,” Whitehead says.[/vc_column_text][/vc_column][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/4-25-13-ccls-data-meeting-flame-retardants-under-the-microscope-1.jpeg” image_size=”full” link=”https://www.sciencedirect.com/science/article/pii/S0160412013000950″ desc=”Printed with permission from “Morphology, spatial distribution, and concentration of flame retardants in consumer products and environmental dusts using scanning electron microscopy and Raman micro-spectroscopy.“ Jeff Wagner, Sutapa Ghosala, Todd Whitehead, Catherine Metayer. Environmental International. September 2013. Copyright 2013 Elsevier” caption_location=”outside-image”][/vc_column][/vc_row][vc_row][vc_column][mk_padding_divider][vc_column_text css=”.vc_custom_1546985157031{margin-bottom: 0px !important;}”]Whitehead’s colleague Jeff Wagner, a microscopist at the California Department of Public Health, used a scanning electron microscope to look for “fingerprints” of these chemical sources on dust particles isolated from the vacuum-cleaner samples.[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column width=”1/4″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/image-2-300×240-1.png” image_size=”medium” link=”https://www.sciencedirect.com/science/article/pii/S0160412013000950″ desc=”Raman spectrum of the dust particle is compared with reference Raman spectra of BDE-209 (Deca BDE), antimony trioxide (Sb2O3), and titanium dioxide (TiO2). Inset shows 5 × reflected light image of the analyzed FR particle. Printed with permission from “Morphology, spatial distribution, and concentration of flame retardants in consumer products and environmental dusts using scanning electron microscopy and Raman micro-spectroscopy.“ Jeff Wagner, Sutapa Ghosala, Todd Whitehead, Catherine Metayer. Environmental International. September 2013. Copyright 2013 Elsevier” caption_location=”outside-image”][/vc_column][vc_column width=”3/4″][vc_column_text css=”.vc_custom_1549604140843{margin-bottom: 0px !important;}”]A dust particle’s color, shape, and form, as well as the chemical elements attached to it, can give researchers clues about where it came from.

For example, stuck to the side of a microscopic chunk of white plastic, the team found traces of a Polybrominated Diphenyl Ether (PBDE), a class of flame retardants that were used to treat household electronics and upholstered furniture. Whitehead and Wagner concluded that this tiny piece of plastic probably got chipped off of some household item, “rubbed off, landed on a carpet and got mixed with dust,” Whitehead says.

The researcher was also looking at whether the flame-retardant chemicals he found in dust could be detected in people’s blood and if those chemicals would affect people’s health.

Research from the California Childhood Leukemia Study that Whitehead co-authored showed that children participating in the study had high levels of PBDEs in the dust from their homes and also in their blood.  On average, homes of children with leukemia contained dust with higher levels of certain PBDEs compared to homes of healthy controls, suggesting that these flame retardants may be risk factors for the disease. All these findings draw connections between consumer products, household contamination, human exposure, and disease.[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][mk_padding_divider][mk_fancy_title font_family=”none”]

What Environmental Regulators Can Do for Us

[/mk_fancy_title][vc_column_text css=”.vc_custom_1546983593245{margin-bottom: 0px !important;}”]Whitehead describes the route of human exposure to flame retardants in house dust as “links in a chain that connect manufacturers of consumer products to regulators that need to make sure those products are safe,” Whitehead says.  The results of this type of research empower regulators to act on protecting the public health.

[/vc_column_text][/vc_column][vc_column width=”1/2″][mk_padding_divider][mk_padding_divider size=”51″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/circle-links-in-chain-nfhkul85ayrp2r7umjcmokwkavrj9ewb48gf7kv0rw.png” desc=”Infographic by CIRCLE” caption_location=”outside-image”][/vc_column][vc_column][vc_column_text css=”.vc_custom_1546984396034{margin-bottom: 0px !important;}”]And indeed, some regulatory progress has been made with PBDEs. They have been phased out in the U.S. because of concerns about their toxicity. In California, some pieces of furniture must now include a consumer label, which shows the presence or absence of chemical flame retardants.  But PBDEs still pose health risks, because some people keep old furniture containing these chemicals and they are pretty hard to get rid of.[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column][mk_padding_divider][mk_fancy_title font_family=”none”]

KIDS ARE AT RISK

[/mk_fancy_title][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][vc_column_text css=”.vc_custom_1546986764174{margin-bottom: 0px !important;}”]PBDEs have a long shelf life, as they are shielded from the sun, the wind and the rain and can stay in homes for years mixing with dust.

This is especially concerning for small children who “put their hands on dust” more frequently, because they are crawling around on the floor and are closer to the ground.

Kids are more likely to accidentally swallow dust and Whitehead’s research has shown that– as a result – children have higher levels of PBDEs in their blood than their mothers do.

Besides flame retardants, the California Childhood Leukemia Study identified other compounds in the home: from Polycyclic Aromatic Hydrocarbons – generated by vehicle exhaust, fire places and stove tops, to pesticides that could be tracked inside on farm workers’ boots and clothes, to nicotine – one trace of so-called “thirdhand smoke”, residual tobacco contamination that remains in a room after the smoke has cleared from the air. No home is without – at least a little – toxic dust.[/vc_column_text][/vc_column][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/circle-leukemia-risk-factors-at-home-myk8tr02tvdvuvo85k4epbr7sa93t7f8le0mjk9uok.png” image_height=”706″ desc=”Infographic by CIRCLE” caption_location=”outside-image”][/vc_column][/vc_row][vc_row][vc_column][mk_padding_divider][mk_fancy_title font_family=”none”]

BRIDGES TURN TO DUST

[/mk_fancy_title][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547487834334{margin-bottom: 0px !important;}”]About a decade ago, the idea of making an impact by protecting children from cancer drove Whitehead to join the field of public health.

While he was trained in civil and environmental engineering for his undergraduate years at the University of Virginia in Charlottesville and during his graduate studies at the University of North Carolina at Chapel Hill, he switched gears.

“A very hands-on course” on exposure assessment taught at UNC-Chapel Hill by environmental health scientist, Dr. Stephen Rappaport, made him change the direction of his education. Whitehead realized that instead of building bridges, storm water runoffs or air pollution monitors, he wanted to work on studies with human participants, with the goal of making “an immediate impact on human lives,” he says.

In 2007, in pursuit of his PhD degree, Whitehead joined Rappaport’s lab group and moved to Berkeley, CA, where both started working on the California Childhood Leukemia Study at the School of Public Health. Whitehead’s role was to analyze data on house dust samples.

The study’s “ingenuity and elegance” – a simple approach for collecting the dust and measuring the chemicals within to assess children’s exposure – had a great appeal to Whitehead.

In his 10th year with the group, Whitehead is now more focused on intervention than on data analysis, which means guiding people towards healthier choices that could help parents protect their children from leukemia and other diseases.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/infographics-bookmark-fan.png” image_size=”full” link=”https://dev-circle-icare.pantheonsite.io/2018/07/31/circle-launches-informational-webpages/” desc=”Infographics by CIRCLE” caption_location=”outside-image”][/vc_column][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/home-sweet-home-rosa-y-carlos-1024×861-1.png” image_size=”large” link=”https://dev-circle-icare.pantheonsite.io/2018/07/31/circle-launches-informational-webpages/”][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1546986423583{margin-bottom: 0px !important;}”]The engaging infographics and videos he is producing with his team give people simple advice on how to avoid exposures to toxic chemicals. These are simple rules that Whitehead believes anyone can follow – advice that he tries to follow in his own home, too.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column][mk_fancy_title font_family=”none”]

MAKING YOUR HOME A HEALTHIER PLACE

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He and his wife Elyse have fragrance-free soaps and laundry detergents with the EPA “safer choice” label. They run a “shoe-free household,” because homes where people take off their shoes at the front door have less dust per square foot inside.

They are careful about what furniture they buy, especially for their kids. When their now 2-year-old son Henry was born, they “went out of their way” to find a crib mattress with no flame retardants in it.

Whitehead makes it a habit to wash his hands after emptying the lint trap from the dryer, as lint accumulates “a load of chemicals” that are present in the home, he says. He uses a vacuum with a HEPA filter and tries to take out the garbage bag full of dust as soon as he is done vacuuming, before his kids – Henry and 4-year-old Eleanor – put their hands in it. You never know with children!

“It is not like I’m paranoid,” Whitehead says. “If you think about it, these are common sense rules.  So why not follow them.”

Yet, Whitehead looks at dust “differently than most people do,” he says. Once he spotted Henry wiping his hand in a circular motion around a tire of Whitehead’s car.

“I was really upset, because it is really dirty and I know there is a ton of messy chemicals from the road that gets onto the tires,” says Whitehead.

And while other parents most likely think, “well, I hope he doesn’t touch my pants or get on the furniture,” Whitehead thought about the studies that showed high levels of Polycyclic Aromatic Hydrocarbons (PAHs) that are present in asphalt.

[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][vc_column_text css=”.vc_custom_1546989705283{margin-bottom: 0px !important;}”]Like any parent, Whitehead is concerned about the world his children will inherit.

“One thing that always seems crazy to me,” says Whitehead, is that persistent chemicals like Polychlorinated Biphenyls (PCB) or insecticides Dichlorodiphenyltrichloroethanes (DDT) banned in the U.S. in the 1970s are still found in people’s homes today.

Worse still, new chemicals are created every year and they’re not all being rigorously tested for toxicity before entering the market.

As awful as this sounds, the goal for Whitehead is not to scare people, but to encourage them to be “hopeful rather than hopeless,” he says. Armed with the information from his research and the practical tips he provides, families can feel empowered to reduce their exposure to toxic chemicals at home.[/vc_column_text][/vc_column][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/smogfactoryemissions-scaled.jpeg” image_size=”full” desc=”Smog Factory Emissions. Photo courtesy of Colin Monteath” caption_location=”outside-image”][/vc_column][/vc_row] READ MORE


Why Cancer?

[vc_row][vc_column][vc_column_text css=”.vc_custom_1547067371681{margin-bottom: 0px !important;}”]by Julia Vassey[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547070389077{margin-bottom: 0px !important;}”]Dr. Catherine Metayer can recall the most challenging moments of her medical career vividly – they came during those harrowing times when she had to deliver patients the bad news.

“I felt it was such a challenging experience when you are being told that you have cancer. It triggers such an emotional and stressful time for you, for your family,” says Metayer.

The first question on the mind of a newly-diagnosed cancer patient is often “why did this happen to me?” Metayer didn’t always have the answers.

Born in France, Metayer has been fascinated with medicine since the age of 13, when she learned of the discoveries of her famous countryman, biologist Louis Pasteur – a pioneer in disease prevention who developed the first vaccines for rabies and anthrax.

But it was cancer that intrigued her most. In the 1990s, she became a resident in oncology and pediatrics and worked at hospitals in the Bordeaux region of France.

Metayer was troubled by those “why me?” experiences with her patients. To find the answers they were looking for, she quit her job in France and left the country to pursue a career in cancer epidemiology in America – the “land of opportunities” for learning about advanced cancer research.

Her personal American Dream was elusive at first. While working on her PhD in Epidemiology at the Tulane School of Public Health in New Orleans, she was just trying to “get by with her poor English,” says Metayer.

She arrived at school well prepared each day, but never uttered a word in class.

“In spite of that, I noticed soon that Americans were welcoming and ready to give me a chance,” she says. “Back then, not so many physicians were seeking a degree in public health, so my contribution was valued and encouraged.”

Metayer studied the immune system’s defense mechanisms against cancer, and was trying to figure out if viruses could trigger leukemia in adults.

After completing her PhD, she joined the National Cancer Institute in Bethesda, MD, to study patients with secondary cancers.

Soon after joining the institute, Metayer found a mentor. Patricia Buffler – a professor and former Dean of the School of Public Health at the University of California, Berkeley – was visiting Bethesda to give a presentation about her search for the causes of childhood cancer, a topic that had been on Metayer’s mind since her days as resident.  The two researchers quickly connected, and Buffler brought Metayer on board her research group in California.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column][mk_fancy_title font_family=”none”]

In the Middle of CIRCLE 

[/mk_fancy_title][vc_column_text css=”.vc_custom_1547068410118{margin-bottom: 0px !important;}”]When Metayer came to Berkeley, most of the world’s cancer research was still focused on adults. Very little was known about the causes of childhood leukemia. Metayer wanted to change that.

So she and Buffler created the Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE), a Children’s Environmental Health Center jointly funded by the National Institute of Environmental Health Sciences and the Environmental Protection Agency. After Buffler’s death in 2013, Metayer carried on their work, assuming the role as the leader of the Center.

“A huge gap in understanding why children have this type of cancer still exists,” Metayer says.

[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][vc_column_text css=”.vc_custom_1547070698523{margin-bottom: 0px !important;}”]Under Metayer’s direction, CIRCLE researchers have been studying unhealthy lifestyles (like cigarette smoking and poor diet), exposure to environmental chemicals (from pesticides, to paint, and air pollution), and prenatal factors (like fetal growth and maternal stress) – which may damage a child’s DNA or alter her immune function possibly leading to cancer.

The scientists have found that exposure to the environmental chemicals accounts for about one-fourth of all childhood leukemia diagnoses. “This is not negligible,” Metayer says.

CIRCLE research also showed that healthier maternal nutrition and folate supplementation with a prenatal vitamin can protect against leukemia, contributing to normal development of the child’s immune system.[/vc_column_text][/vc_column][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/a-story-of-health-book-1.png” image_size=”full” link=”https://dev-circle-icare.pantheonsite.io/2017/10/05/latest-chapter-of-a-story-of-health-released/” target=”_blank” desc=”eBook with videos, infographics and articles by CIRCLE” caption_location=”outside-image”][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547070837358{margin-bottom: 0px !important;}”]Because the disease can start during pregnancy or even before conception, CIRCLE uses an innovate approach to examine chemical exposures that may have emerged prenatally. The center takes samples from newborn dried blood spots that are routinely collected and stored by the State of California to screen infants for genetic disorders. CIRCLE studies showed that paternal preconception smoking was associated with the increased risk of childhood leukemia.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column][mk_fancy_title font_family=”none”]

Orchestrating International Collaboration

[/mk_fancy_title][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547247718780{margin-bottom: 0px !important;}”]Leukemia is the most common type of childhood cancer, but it is still a relatively rare disease. Every year in America, about one-and-a-half million adults are diagnosed with cancer, while fewer than twenty thousand children get the disease. Studying a rare disease like childhood leukemia poses methodological challenges for Metayer and her center.

“Our research always goes through a very stringent peer review,” says Metayer.  The small number of sick patients available for participation means her studies tend to have small sample sizes, which can draw skepticism from reviewers.

To overcome this problem and make the findings more credible, ten years ago, Metayer and Buffler decided to expand the pool of patients and look at the global experience with childhood leukemia.[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][vc_column_text css=”.vc_custom_1547247703853{margin-bottom: 0px !important;}”]The CIRCLE researchers brought together a team of international collaborators – from France, Canada, and Australia – who were asking the same research question as CIRCLE: what are the causes of childhood leukemia?

“So we sat down and asked ourselves what would it take to work together,” says Metayer.

The researchers decided to form the Childhood Leukemia International Consortium (CLIC) where members would pool data from their individual studies to learn more about the risk factors for childhood leukemia and help develop strategies to prevent future cases of the disease.[/vc_column_text][/vc_column][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/2016clicmtg_houstontexasusa-scaled.jpeg” image_size=”full” desc=”CLIC meeting, Houston, Texas, 2016″ caption_location=”outside-image”][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2022/04/map-of-clic-1.png” image_size=”full” desc=”CLIC organizations worldwide” caption_location=”outside-image”][/vc_column][vc_column width=”1/2″][vc_column_text css=”.vc_custom_1547069065302{margin-bottom: 0px !important;}”]Within a decade, the scope of CLIC’s research has grown from four studies to 30 with 40,000 leukemia patients now enrolled around the world.

Metayer, who is the chair of the consortium, says that the CLIC researchers really “clicked.”

At times, Metayer feels like a “conductor” leading an orchestra of investigators. Each player has a part and together they are creating a symphony. The rich variety of data, brought together from different countries, brings more insight and helps researchers decipher the true triggers of childhood leukemia.[/vc_column_text][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547069158860{margin-bottom: 0px !important;}”]“The scientists volunteer for the consortium. They are very motivated. They work out of their hearts” to share resources and expertise, says Metayer.

The great success of the international consortium is among Metayer’s brightest career highlights.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column][mk_fancy_title font_family=”none”]

Leukemia in Latinos

[/mk_fancy_title][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][vc_column_text css=”.vc_custom_1547069699521{margin-bottom: 0px !important;}”]Rates of childhood leukemia are on the rise in the U.S., especially among Latino children. In California, the number of Latino kids with acute lymphoblastic leukemia has increased by 35 percent over the past 40 years.

The reasons for the rising rates are not well understood, but CIRCLE researchers have some leads.  Latinos in California can face work-related health hazards. CIRCLE researchers discovered that Latino children whose fathers are exposed at work to chlorinated solvents – well-established carcinogens in adults – are at higher risk of getting leukemia. “Because solvents are highly volatile and quickly dissolve, we think that they impact the father directly by damaging his sperm cells before conception,” says Metayer.

But the discovery of the effect from solvent exposures brought an array of other questions: “Why only Latino fathers? Do they have different work habits?

[/vc_column_text][/vc_column][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/4-25-18-hospital-bed-infographic-8-5×11-1.png” image_size=”full” link=”https://dev-circle-icare.pantheonsite.io/start-now/” desc=”Infographic by CIRCLE” caption_location=”outside-image”][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547069710716{margin-bottom: 0px !important;}”]Are they exposed to higher levels of those chemicals? How well do they use protection equipment? Is there an issue about genetic susceptibility when the body breaks down those chemicals?” Metayer wonders.

Pesticides exposure is another problem uniquely affecting Latino communities – one that the CIRCLE researchers are paying close attention to. In California, 75 percent of the workforce in agricultural fields is Latino. These workers are constantly exposed to pesticides. Accidental inhalation of the sprayed chemicals is common.

To make matters worse, farm workers may track pesticides home on boots and clothes, exposing their children to toxic chemicals.

Research from CIRCLE and CLIC investigators has consistently demonstrated that residential pesticide use during pregnancy can increase a child’s risk for leukemia, but these troubling findings are sometimes overlooked.

Next to adult cancers, asthma or autism, leukemia research that the CIRCLE center is focused on is “just a little drop in the ocean for regulators and funders,” says Metayer. That’s why pushing regulating agencies to put restrictions in place for the use of certain environmental chemicals has always been a challenge.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column][mk_fancy_title font_family=”none”]

Life After Leukemia

[/mk_fancy_title][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547246965693{margin-bottom: 0px !important;}”]Since the 1990s, the quality of leukemia treatment has significantly improved and the survival rate has increased, but the consequences of childhood leukemia remain a heavy burden. Long-term and secondary effects that often appear later include diminished neurocognitive development, depression, and obesity.

While continuing her quest for what triggers the disease, Metayer’s new aspiration is to look at children-survivors who have undergone cancer therapies.

The researcher says a lot of effort has been put into studying the side effects of cancer therapies, but little attention has been paid to the lifestyle and environmental exposures of patients after cancer treatment.

According to Metayer, many survivors – mostly Latino children – experience increased rates of obesity and neurocognitive disabilities that could also be explained by poor diet and the presence of toxic chemicals. Children who survive leukemia – especially those living in poor conditions – are potentially exposed to neurotoxic substances like flame retardants, air pollution, and lead.

“I want to bring the world of environmental health to cancer survivor studies and find out whether the environmental impacts those long-term sequelae of leukemia,” says Metayer.

Metayer is actively pursuing funding to support this next phase of her research.[/vc_column_text][/vc_column][/vc_row] READ MORE


CIRCLE, Highlights

[vc_row][vc_column][vc_column_text css=”.vc_custom_1547073227092{margin-bottom: 0px !important;}”]To combat leukemia, the most common and deadly childhood cancer, the leading researchers at the University of California, Berkeley School of Public Health created CIRCLE – the Center for Integrative Research on Childhood Leukemia and the Environment. Since 2008, the CIRCLE investigators have been discovering how environmental and genetic risk factors interact to cause childhood leukemia with the goal of preventing children from getting the disease.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2019/01/istock_14054649_large-mzvgvxonasi9zqcjqpr7lo35496rihm9qh11tf5a5o.jpeg” desc=”Unaligned DNA sequences viewed on LCD screen” caption_location=”outside-image”][/vc_column][vc_column width=”1/2″][vc_column_text css=”.vc_custom_1547246316120{margin-bottom: 0px !important;}”]For over 10 years, the center has been gathering its data from a long-standing National Institutes of Health-funded study in 35 counties of the San Francisco Bay Area and the Central Valley. CIRCLE has also been collecting biospecimens and analyzing data from a California statewide record linkage between birth and cancer registry records, pinpointing all childhood and adolescent cancer cases since 1988.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column width=”1/2″][mk_padding_divider][vc_column_text css=”.vc_custom_1547073978558{margin-bottom: 0px !important;}”]Leukemia is a rare disease. This makes it difficult to collect information on a large enough number of patients to determine which factors contribute to the risk if getting it. But CIRCLE has found a way to overcome this hurdle.

10 years ago, the CIRCLE leader Catherine Metayer founded the Childhood Leukemia International Consortium a collaboration of over 30 case-control studies from North and South America, Europe, Africa, and Oceania that is able to combine data from many studies to identify risk factors for childhood leukemia.[/vc_column_text][mk_padding_divider][/vc_column][vc_column width=”1/2″][mk_padding_divider][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2022/04/map-of-clic-1.png” image_size=”full” desc=”Locations of Studies Participating in the Childhood Leukemia International Consortium” caption_location=”outside-image”][/vc_column][vc_column][/vc_column][/vc_row][vc_row][vc_column][vc_column_text css=”.vc_custom_1547246413034{margin-bottom: 0px !important;}”]CIRCLE relies on contributions from stellar scientists, public health experts and patients – the clinical investigators and staff who have helped recruit study participants from their hospitals, the researchers from the Childhood Leukemia International Consortium, the staff from the California Department of Public Health, and, most importantly, the families who have agreed to participate in the research to help find the causes of childhood leukemia.[/vc_column_text][mk_padding_divider][/vc_column][/vc_row][vc_row][vc_column width=”1/4″][mk_image src=”https://live-circle-icare.pantheon.berkeley.edu/wp-content/uploads/2015/06/cm_white-1-e1652578135234.png” image_size=”medium” desc=”Catherine Metayer” caption_location=”outside-image”][/vc_column][vc_column width=”3/4″][vc_column_text css=”.vc_custom_1547074561528{margin-bottom: 0px !important;}”]CIRCLE is jointly funded by the National Institute of Environmental Health Sciences (NIEHS) and the U.S. Environmental Protection Agency (EPA).  The Center is directed by Dr. Catherine Metayer (MD, PhD) an Adjunct Professor in the School of Public Health at UC Berkeley.

In addition to the NIEHS-EPA funding, childhood leukemia research conducted by CIRCLE investigators has been partially-supported by the National Cancer Institute, Alex’s Lemonade Stand Foundation, Children with Cancer – UK, and the Tobacco-Related Disease Research Program.[/vc_column_text][/vc_column][/vc_row] READ MORE