Germ-free childhoods followed by infections later in life can trigger the onset of childhood leukemia, a new study suggests.
The paper, published Monday in the journal Nature Reviews Cancer, finds that acute lymphoblastic leukemia, the most common type of childhood cancer, is caused by a two-step process.
The first step is a genetic mutation before birth that predisposes a child to the risk of developing this form of leukemia. The second step is exposure to certain infections later in childhood, after clean early childhoods that limited exposure to infections.
More specifically, children who grew up in cleaner households during their first year and interacted less with other children are more likely to develop acute lymphoblastic leukemia, the paper says.
The author, Institute of Cancer Research Professor Mel Greaves, suggests the cancer could be preventable.
Greaves reviewed more than 30 years of research, including his own, on the genetics, cell biology, immunology, epidemiology and animal modeling of childhood leukemia and reached this conclusion. Greaves said he had long wondered "why or how otherwise healthy children develop leukaemia and whether this cancer is preventable."
"This body of research is a culmination of decades of work, and at last provides a credible explanation for how the major type of childhood leukaemia develops," he said in a statement. "The research strongly suggests that (this cancer) has a clear biological cause, and is triggered by a variety of infections in predisposed children whose immune systems have not been properly primed."
However, other experts warn that more specifics needs to be confirmed and emphasize that hygiene and safety are still crucial.
Acute lymphoblastic leukemia, known as ALL, is a form of blood cancer that is most often diagnosed in children ages zero to 4 years old, though older children and adults can also be diagnosed. It develops quickly, over days or weeks, building up in the blood and spreads to other parts of the body, including the lymph nodes, liver and nervous system. The main form of treatment is chemotherapy.
Rates of the disease are increasing globally. One study estimated there were 53,000 cases worldwide in 2016. Around 5,960 new cases of ALL are estimated to occur in the United States in 2018, with 1,470 deaths according to the American Cancer Society. Each year, around 810 people are diagnosed in the UK, according to Cancer Research UK.
While a genetic mutation plays a role in predisposing someone to the disease, just 1% of children born with this mutation go on to develop the disease, according to the paper. Rates are more common in advanced, affluent societies, which suggests the second step could be caused by factors relating to modern life.
Previous claims have linked electromagnetic waves and other environmental factors to the disease, but Greaves dismissed this link in his paper.
The body of research "busts some persistent myths about the causes of leukaemia, such as the damaging but unsubstantiated claims that the disease is commonly caused by exposure to electro-magnetic waves or pollution," said Greaves.
Greaves instead believes that when a baby is exposed to infections during its first year, its immune system is strengthened. But later infections, without the initial priming, can trigger leukemia in those with the genetic mutation.
Population studies have found that early exposure to infection in infancy such as day care attendance and breastfeeding can protect against ALL, probably by priming the immune system, according to the study.
Greaves emphasized that infection as a cause applies only to ALL. Other types of leukemia, including infant leukemia and acute myeloid leukemia, probably have different causal mechanisms.
"Preventing childhood leukaemia would have a huge impact on the lives of children and their families in the UK and across the globe," said Paul Workman, chief executive of the Institute of Cancer Research, London.
However, other experts are more cautiously hopeful, emphasizing that genetics and pure chance are still significant factors for developing ALL.
"If we could stop this type of leukaemia from happening in the first place it would be enormously exciting, but many more questions still need to be answered in the research lab before we will know for sure whether that could become a reality," said Alasdair Rankin, director of research at blood cancer charity Bloodwise.
"There is no proven link yet with a specific infection," said Dr. Donna Lancaster, consultant pediatric oncologist at the Royal Marsden NHS Foundation Trust. "This [new study] still needs further investigation and any exposure of young children to infection has to be balanced with the risk of the infection.
Sheena Cruickshank of the British Society for Immunology also pointed to the potential risk of exposing children to infections, emphasizing that hygiene and safety are still crucial to maintain.
"It's also important to remember that infections themselves can pose a significant risk for young babies with a developing immune system," said Cruickshank in a statement. "Parents should not be unduly alarmed by this review."
The research may be a step toward developing preventative measures. However, Charles Swanton, chief clinician of Cancer Research UK, stressed that the causes and prevention methods are still unconfirmed.
"This research sheds light on how a form of childhood blood cancer might develop, implicating a complex combination of genetics and early exposure to germs, dirt, and illness," Swanton said. "We want to assure any parents of a child who has or has had leukaemia, that there's nothing that we know of that could have been done to prevent their illness."
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