High Birthweight and Cancer: Evidence and Implications

Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta

“…Moreover, high birthweight, especially birthweights that would categorize babies as LGA, is associated with an increased risk for disease in both children and adults. Previous work has shown high birthweight as a risk factor for insulin resistance 11 and obesity, 12 as well as for a number of cancers, 13 and it is clear that glucocorticoid signaling can play a role in these pathologic processes. While normal physiological levels of glucocorticoids and GR are essential for metabolic control, altered glucocorticoid action has also been shown to be associated with a variety of metabolic diseases such as obesity and type 2 diabetes.…”

“…10 Previous studies have shown high birthweight as a risk factor for insulin resistance, 11 obesity 12 and cancers such as leukemia and breast, prostate and colon cancers. 13 Studies to determine the potential risk factors for mothers of large for gestational age (LGA) babies are ongoing 10 and more research is needed to identify potential risk factors behind this developmental outcome.…”

High birth weight as an important risk factor for infant leukemia

“…Other mechanisms suggested for the association with birth weight include the supposition that IL is initiated by aberrant gene fusions, mainly with MLL rearrangements (Ross et al, 1996a;Alexander et al, 2001). Interactions between high birth weight, prenatal oestrogen exposure and leukaemia risks have also been suggested (Ross et al, 1996a;Baik et al, 2005;Ross, 2006).…”

“…It has been suggested that insulin-like growth factor-1 (IGF-1) promotes a proliferative advantage to damaged cells (Ross et al, 1996a;Ross, 2006). The link between birth weight, steroid hormones in intrauterine life such as IGF-1 and cancer risk indicates that such hormones tend to increase the number of stem cells and, by extension, more proliferating immature cells are exposed to harmful events, and consequently become more susceptible to malignant transformation (Cavalieri et al, 1997;Boyne et al, 2003).…”

Very high birth weight of offspring is associated with an increased risk of leukemia in their mothers: Results of a population-based cohort study

“…Factors related to high birth weight include maternal diabetes, advanced maternal age, maternal height, BMI and weight gain during pregnancy as well as gestational age and the sex of the child. [4,5,6]. Postulated mechanisms for the association of leukemia and birth weight have included exposure to growth factors (eg IGF-1) related to somatic growth and leukemogenesis [7], possible common genetic mechanisms or higher cell numbers in larger individuals providing increased opportunity for genetic errors.…”