Birthweight
Birthweight is one of the most commonly studied perinatal risk factor of
childhood cancer. High birthweight as a proxy of fetal macrosomia has
been found to increase the risk of several cancers, including leukemia,
CNS tumors, neuroblastoma, colorectal and breast cancer. Both
genetics/epigenetics and environmental factors have been proposed to
underlie these associations, whereas growth factors (IGF-1 and IGF-2)
seem to play a crucial role in carcinogenesis by stimulating mitogenesis
and cell cycle progression, while inhibiting apoptosis. Thus, IGFs can
lead to an increase in the number of hematopoietic stem cells and to the
promotion of malignant transformation of some of them, which may
subsequently expand to pre-leukemic and then to overt leukemic.
Moreover, it is well known that fetal macrosomia is associated with
increased rates of cesarean delivery. An increased risk of leukemia in
children born by cesarean section has been reported after controlling
for birthweight, which has been attributed to altered microbiota
colonization or/and to the lack of increased cortisol levels that could
eliminate preleukemic and leukemic cells (the “adrenal hypothesis”).
Furthermore, given the global increase in the incidence of obesity and
the effect of overweight/obesity during pregnancy on high birthweight,
the potential association between fetal macrosomia and childhood cancer
risk merits further investigation. It would be interesting to explore
whether primary prevention of overweight/obesity may indirectly reduce
the incidence of childhood cancer.