The causes of cancer in children are fundamentally distinct from those responsible for most adult malignancies. While adult cancers often develop after decades of exposure to environmental factors and lifestyle risks, pediatric cancers typically arise from genetic changes that occur much earlier in life. These early-onset diseases are more closely tied to accidental events during rapid growth or inherited genetic predispositions. This article explains the specific etiologies that lead to cancer in the young.
Spontaneous Errors in Cell Development
The most common cause of cancer in children is the random, non-inherited genetic change known as a somatic mutation. These mutations are accidents that happen during the body’s massive program of cell division and growth. A fertilized egg cell must divide trillions of times to form a baby, and this extensive replication process inevitably results in errors.
Every time a cell copies its DNA, a mistake can be made in the genetic code. Although the cell has sophisticated repair mechanisms, some errors escape correction, leading to a permanent genetic change. When these errors occur in genes that regulate cell growth or division, they can initiate the cancer process. This developmental origin means the initial “hit” often happens during the active growth phases of fetal development or infancy.
For instance, childhood acute lymphoblastic leukemia (ALL), the most frequent pediatric cancer, is often traced back to a genetic error that occurred in a blood cell precursor while the child was still in the womb. These mutations are de novo, meaning they are new to the child and were not present in the parents’ germline DNA. The resulting cancer is not a consequence of lifestyle or accumulated damage.
These spontaneous genetic changes often manifest as structural variants, where large segments of DNA are deleted, duplicated, or rearranged. These large-scale changes can affect genes responsible for the proper differentiation and growth of tissues, such as the nervous system or bone. The majority of pediatric cancer cases occur without any clear external cause or family history.
Inherited Genetic Syndromes
A smaller, yet significant, portion of pediatric cancers is directly linked to an underlying inherited genetic predisposition. These cases involve a germline mutation, meaning the genetic change was present in the egg or sperm cell and was passed down from a parent to the child. Such inherited syndromes account for approximately 5 to 10% of all childhood cancers.
A child born with a germline mutation has a faulty copy of a gene in every cell of their body, which significantly increases their lifetime risk of developing cancer. This condition is often referred to as a cancer predisposition syndrome. For example, Li-Fraumeni syndrome is caused by a mutation in the TP53 gene, which normally acts as a tumor suppressor. Children with this syndrome have a high risk of developing various cancers, including sarcomas and brain tumors, often at a young age.
Another example is hereditary retinoblastoma, a cancer of the eye seen almost exclusively in young children, which results from a mutation in the RB1 gene. Children born with Down syndrome (Trisomy 21) also have an increased likelihood of developing certain types of leukemia. While these inherited conditions confer a high risk, a second “hit”—a spontaneous somatic mutation in the remaining healthy gene copy—is still required for the cancer to fully develop.
The Limited Role of Environmental Exposure
In contrast to the dominant role of internal genetic factors, the influence of external environmental exposures on the development of most childhood cancers is considered minor. Children have not lived long enough to accumulate the extensive DNA damage from carcinogens that drives the majority of adult cancers. The link between everyday environmental factors and pediatric cancer incidence remains weak or unproven for most types.
However, specific and intense exposures have been associated with a small number of pediatric cases. High-dose radiation exposure, such as from previous medical treatments, is a known factor that can induce a secondary cancer years later. Certain chemical exposures, like parental exposure to specific agents before conception or a child’s exposure to high levels of some pesticides, have been explored as potential risk factors.
Infections also play a small role, with viruses like Epstein-Barr virus linked to some lymphomas and human immunodeficiency virus (HIV) increasing the risk for specific, rare cancers in children. Despite these limited associations, the consensus remains that random genetic errors and inherited predispositions are the overwhelming drivers of pediatric malignancy.
How Childhood Cancer Differs from Adult Cancer
The fundamental differences in cause lead directly to pronounced differences in the types and behaviors of pediatric and adult cancers. Adult cancers are predominantly carcinomas, which arise from epithelial cells lining organs like the lung, breast, and colon. These are typically slow-growing diseases resulting from the accumulation of numerous genetic mutations over many decades.
In contrast, cancers in children are often leukemias, lymphomas, sarcomas, and blastomas, which originate from embryonic or developmental tissues. These cancers typically possess a lower number of overall genetic mutations compared to adult tumors. They are characterized by defects in growth and differentiation pathways, often involving specific chromosomal translocations or gene fusions that create powerful oncogenes.
Pediatric cancers are diseases of dysregulated development, where the cancer cell resembles an immature or precursor cell that failed to complete differentiation. For example, neuroblastoma arises from immature nerve cells, and Wilms tumor originates from immature kidney cells. This distinction means that pediatric cancers are generally more aggressive but often more sensitive to chemotherapy, leading to higher overall survival rates compared to many adult cancers.