One of the hardest parts of unraveling childhood cancers is understanding what causes them. In recent years, evidence has been mounting that cancer and many other chronic diseases begin early in life – and perhaps even in utero. To untangle some of these early causes of cancer in children and young adults, Stanford epidemiologist and family physician Casey Crump, MD, PhD, is partnering with researchers at Lund University in Sweden, a working relationship was set up by Marilyn Winkleby, PhD, MPH, professor emeritus of medicine here. The team is using Sweden’s national registries for birth certificates and medical records to track how factors during gestation and soon after birth – called perinatal factors – affect cancer risks.
Because Sweden has a national health care system, it’s relatively easy to track the course of illness in individuals. By comparison, the U.S.’s health care system is fragmented across dozens of health care providers and insurers, so getting medical records for a single person that might span decades is a much more difficult prospect.
Crump’s team is focusing on cancers that are common in childhood and early adulthood: brain tumors, leukemia and lymphoma among them. Two papers published earlier this year examine how the time of year a child is born affects cancer risk. The most recent, published ahead of print in April in the International Journal of Cancer, examined whether the season of birth was linked to the risk of developing either Hodgkin’s lymphoma or non-Hodgkin’s lymphoma later in life. Crump explained:
Lymphomas are among the most common cancers in childhood but the causes are still largely unknown. It’s been hypothesized that infectious exposures, such as Epstein Barr virus and others may play an important role, but it’s still unclear what the critical age window of susceptibility might be. We had an opportunity to use season of birth from birth records as a proxy for infectious exposures in the first few months of life, and see the relationship between that and subsequent risk of Hodgkin’s and non-Hodgkin’s lymphoma – following these people from birth through childhood and on into young adulthood.
The researchers found that children born in spring or summer had a higher risk of developing non-Hodgkin’s lymphoma later in life compared to kids born in winter. The team didn’t find any similar seasonal pattern for risk of Hodgkin’s lymphoma. The results lend additional support to the “delayed exposure hypothesis.” Children born in spring or summer may not be exposed to critical pathogens during a critical early period of immune system development, leaving them vulnerable later in life. Children born in the fall or winter, by comparison, do get that important exposure at just the right time. Crump was quick to note that season of birth provides only a rough estimate of these exposures, since the team didn’t have accurate measures of exposures to Epstein Barr or other viruses, but he also added that these results “shed additional light on possible pathways of risk that may contribute to the development of non-Hodgkin’s lymphoma.”
A similar study published in January in the International Journal of Epidemiology found that children born in spring and summer had a higher chance of developing melanoma later in childhood or early adulthood. The team hypothesized that spring and summer babies are exposed to more UV radiation in warm summer months in the first few months of life – an exposure that fall and winter babies are less likely to have.
Both studies are part of a larger effort of the team to understand perinatal risk factors for cancers. Another intriguing connection is how gestational growth rate is linked to cancer risk. In utero, hormones direct a developing fetus’s cells to grow. But those same hormones are known to be linked to the out-of-control growth of cancer cells. Previous research has examined the link between cancer risk and gestational weight as a proxy for growth-related hormone levels, but this new research is an attempt to tease out more precise pathways involved in setting cancer growth going in the first place.
This latest research is an offshoot of Crump’s earlier research, which included looking at how preemies’ mortality rates later in life differed from normal gestational age infants. He expects to have further results on cancer risks and gestational growth rate early next year. He says he considers the partnership with Lund University researchers and their access to Sweden’s rich source of health data “a great opportunity to address important unanswered questions” in cancer research.
Previously: Preemies face increased risk of death in early adulthood, Stanford study finds, The spark of a cancer revolution, and Cancer drug shortage implicated in relapses among young Hodgkin lymphoma patients
Photo collage by Predavatel