The paradox of leukemia and cleanliness

For most of our lives, it has been engrained in us that illnesses are primarily caused by unhygienic environmental factors. However, in the case of leukemia, recent studies have shown that it may very well be the opposite. With an annual incidence in the United States of approximately 3,800 children per year, leukemia is the most common form of pediatric cancer. Contrary to popular belief, leukemia is actually a general term used to describe cancer that affects blood-forming tissues such as bone marrow or lymphatic tissues. It encompasses a variety of cancers such as acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and chronic lymphocytic leukemia (CLL). 

ALL is the most common form of leukemia found in children and has risen by 55 percent in annual cases since 1975. While modern treatment options cure 80 to 90 percent of pediatric ALL patients, long-term consequences, such as declines in neurocognitive function, endocrine health, and overall health, continue to affect patients well beyond their treatment period, thus giving rise to the need for preventative care. 

While modern treatment options cure 80 to 90 percent of pediatric ALL patients, long-term consequences, such as declines in neurocognitive function, endocrine health, and overall health, continue to affect patients well beyond their treatment period, thus giving rise to the need for preventative care

One outstanding hypothesis labeled the “infection hypothesis” suggests that childhood leukemia may be the result of an abnormal response to common infections. There are two models of this hypothesis: epidemiologist Leo Kinlen’s population-mixing hypothesis and British biologist Mel Greaves’s delayed infection hypothesis. Kinlen’s hypothesis suggests that a lack of herd immunity combined with the migration and mixing of different populations leads to higher incidence rates of leukemia across the board. Greaves’s hypothesis, which is more specific to ALL, claims that the immune system anticipates and requires microbial infectious exposure either in-utero or during infancy, which has lasting effects on immune function and general health. Though research cannot pinpoint specific infections that are guaranteed to prevent childhood leukemia, these hypotheses indicate that an infant’s environment plays a bigger role in the development of leukemia than their genetics. In fact, a 2013 study found that less than 10 percent of childhood leukemia is attributed to genetic risk factors. 

Though research cannot pinpoint specific infections that are guaranteed to prevent childhood leukemia, these hypotheses indicate that an infant’s environment plays a bigger role in the development of leukemia than their genetics.

Epidemiological evidence in multiple studies conducted with regard to postnatal patterns of infection supports Greaves’s hypothesis. A 2005 study used data compiled by the UK Children’s Cancer Study Group in the 1990s for analysis of the delayed infection hypothesis in the context of daycare attendance during the infants’ first 12 months of life. The study showed that formal daycare attendance, defined as attending a facility with at least four other children two times a week, within the first three to twelve months of life had a significant protective effect on the risk of developing ALL and B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL), a form of ALL where an excess of B-cell lymphoblasts are found in the bone marrow and blood. However, later research conducted in California, Scandinavia, and France suggest otherwise, causing debate about the reliability of using daycare attendance as a metric for testing Greaves’s hypothesis. Nevertheless, between assessing daycare attendance and recalling particular infections in infancy, daycare attendance is the more acceptable metric, as it relies on raw data in comparison to potentially inaccurate parental recall. 

Another potential postnatal pattern of infectious exposures in infancy that Greaves analyzed is birth order. Several studies in California, the United Kingdom, and France conducted between 2001 and 2015 found a strong correlation between birth order and ALL risk, with firstborn children being at higher risk for leukemia. Furthermore, breastfeeding and the method of delivery also impact a child’s risk for ALL. For example, multiple studies have reported a significantly increased risk of ALL with caesarean delivery, which bypasses the microbial exposures associated with normal vaginal birth. Postnatal decisions, such as the length of breastfeeding, also play a big role in infants’ risks of ALL. Across 17 case studies, it was found that there is a 10 to 20 percent reduced risk of ALL when the breastfeeding period is longer than six months. 

Across the three postnatal patterns of infections Greaves analyzed, it was confirmed that there indeed was a correlation between the environment during infancy and the risk of ALL. Thus, he inferred that clean homes also contributed to the risk of ALL. Against most conventional public health advice, perhaps experiencing some infections and dirt would be a beneficial, calculated risk in childhood.

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