Fetal growth and the risk of childhood CNS tumors and lymphomas in Western Australia

Abstract

The etiology of childhood cancers is largely unknown, although the early age at diagnosis has led to particular interest in in utero and perinatal factors. Birth weight is the most frequently studied perinatal factor in relation to risk of childhood cancers, and results have been inconsistent. We investigated whether the risk of CNS tumors and lymphomas in children was associated with three measures of the appropriateness of intra-uterine growth: proportion of optimal birth weight (POBW), birth length (POBL) and weight for length (POWFL). A cohort of 576,633 infants born in Western Australia in 1980-2004 were followed from birth to diagnosis of a CNS tumor (n 5 183) or lymphoma (n 5 84) before age 15, death, or December 31, 2005, and analyzed with Cox regression. Overall, there was little evidence of any association between fetal growth and risk of CNS tumors, although risk of ependymoma/choroid plexus tumors was positively associated with POBL and negatively associated with POWFL. The risk of Hodgkin and Burkitt lymphoma increased with increasing fetal growth among boys only, whereas the increased risk observed with nonHodgkin lymphoma was only in girls. These associations between fetal growth and disease risk were also observed among children not classified as high birth weight, suggesting that accelerated growth is more important than birth weight per se. Results were similar when cases were compared with their unaffected siblings, suggesting that the increased growth associated with cancer risk was not general to the family. The associations we observed are consistent with causal pathways involving fetal growth factors.

Fetal Growth and Childhood Cancer: A Population-Based Study

“…An Australian study on fetal growth and risk of childhood CNS tumors found little evidence of an overall association, using relatively novel measures of fetal growth (proportion of optimal birth weight, length, and weight for length). 23 In contrast, a Nordic study (using part of the current data set) found a U-shaped relation between birth weight and CNS tumors.…”

“…22,23 A 2012 meta-analysis, encompassing 2 cohort and 7 case-control studies, found no statistically significant associations between birth weight and lymphoma in general or between birth weight and major lymphoma categories (non-Hodgkin' s and Hodgkin' s lymphoma). 5 A national Swedish cohort study, overlapping partly with the Swedish data in our study, reported that increased fetal growth was associated with non-Hodgkin' s lymphoma in early life, independent of gestational age and other perinatal factors.…”

Fetal growth and the risk of childhood non-CNS solid tumours in Western Australia

“…We previously reported an increased risk of ALL (acute lymphocytic leukaemia) (Milne et al, 2007), of Hodgkin lymphoma and Burkitt lymphoma among boys, and of non-Hodgkin lymphoma among girls (Milne et al, 2008) in association with increasing proportion of optimal birth weight, a measure of the appropriateness of fetal growth (Blair et al, 2005). These findings are consistent with a biologically plausible mechanism of accelerated growth associated with growth factors in normal as well as cancer cells.…”

“…As in our approach with childhood ALL (Milne et al, 2007), CNS tumors and lymphomas (Milne et al, 2008), we aimed to distinguish an effect of high birth weight per se and one with accelerated growth. We restricted the univariate regression analysis of POBW to, in turn, children with birth weights below two commonly used definitions of high birth weight: 43500 and 44000 g. The positive associations observed between POBW and retinoblastoma and rhabdomyosarcoma were also observed among children with birth weights o3500 and o4000 g: retinoblastoma (HR: 1.39, 95% CI 0.82 -2.36 and HR: 1.32, 95% CI 0.89 -1.95, respectively); and rhabdomyosarcoma (HR: 1.53, 95% CI 0.82 -2.86 and HR: 1.55, 95% CI 1.00 -2.40, respectively).…”

“…As with ALL (Milne et al, 2007) and lymphomas (Milne et al, 2008), there was a positive association between at least one measure of IUG and risk of retinoblastoma and rhabdomyosarcoma. We found no evidence of an association between IUG and risk of neuroblastoma and, unlike previous studies (Leisenring et al, 1994;Yeazel et al, 1997;Schuz et al, 2001), we found no association between IUG and the risk of Wilm's tumour.…”