Genetic and Nongenetic Risk Factors for Childhood Cancer

Abstract

Summary The causes of childhood cancer have been systematically studied for several decades, but apart from high-dose radiation and prior chemotherapy there are few or no strong external risk factors. On the other hand, inherent risk factors including birth weight, parental age, and congenital anomalies are consistently associated with most types of pediatric cancer. Rare, highly-penetrant syndromes have long been known to cause a small proportion of cancers but recently the contribution of common genetic variation to etiology has come into focus through genome wide association studies. These have highlighted genes not previously implicated in childhood cancers and, surprisingly, have suggested that common variation explains a larger proportion of childhood cancers than adult. Rare variation and non-Mendelian inheritance, such as through maternal genetic effects or de novo germline mutations, may also contribute to childhood cancer risk but have not been widely examined to date.

Maternal pre-pregnancy and gestational diabetes, obesity, gestational weight gain, and risk of cancer in young children: a population-based study in California

“…We also excluded children that were missing sex (n=3), births that were likely not viable (gestational age <20 weeks and/or birthweight <500g) (n=169), and children diagnosed with Down syndrome (n=151). The latter was done because Down syndrome is a strong risk factor for childhood cancer [3] and potentially related to pregnancy-related characteristics, including maternal obesity [38]. Additionally, mothers who had extreme or implausible BMI values (<17 kg/m 2 or > 45 kg/m 2 ) and gestational weight gain values (< −2 kg or >32 kg) were excluded.…”

“…In large part, the factors contributing to these increasing trends are largely unknown, as few risk factors for childhood cancer have been established [2]. Known risk factors include ionizing radiation, prior chemotherapy, and congenital genetic syndromes such as Down syndrome, neurofibromatosis, Fanconi anemia, and Bloom Syndrome, though these are only suspected to contribute to 5% to 10% of childhood cancers [3]. …”

Exposure to ambient dichloromethane in pregnancy and infancy from industrial sources and childhood cancers in California

“…Evidence is slowly growing for several possible causal associations. Ionizing radiation and prior chemotherapy have been shown to cause childhood cancers (Spector et al, 2015). In addition, males have a slightly higher risk of developing most childhood cancers.…”

“…In addition, males have a slightly higher risk of developing most childhood cancers. Older parental age and race/ethnicity also play a role in the development of malignancies in infancy with highest rates observed among whites (Spector et al, 2015). …”

A childhood acute lymphoblastic leukemia genome-wide association study identifies novel sex-specific risk variants

“…[1] While overall 5-year survival rate has improved to 80% on average, the US annual incidence rate increased by 0.8% per year from 1975 to 2012 in children aged 14 years and younger. [1,2] . Like many other diseases and cancers, childhood ALL risk shows consistent sex differences.…”