The epidemiology of hepatoblastoma

Abstract

Few causes of hepatoblastoma have been conclusively identified, mainly due to the extreme rarity of the disease. Inherited conditions including Familial Adenomatous Polyposis and Beckwith-Wiedemann Syndrome dramatically raise risk of hepatoblastoma but account for few cases overall. A small number of case-control studies investigating risk factors for sporadic hepatoblastoma have been conducted to date. Although most of these studies feature fewer than 200 cases, several clues have emerged. Most notably there is a roughly 20-fold increased risk of hepatoblastoma among children with very low birth weight (<1,500 g) and a doubling of risk among those with moderately low birth weight (1,500-2,500 g). A modicum of evidence points to a possible role of parental tobacco use prior to or during pregnancy in the causation of hepatoblastoma as well.

The genetic and epigenetic landscapes of hepatoblastomas

“…Several studies have investigated the role of environmental factors during pregnancy that could be causally related to HB development [5], including pre-eclampsia [25], maternal overweight condition during pregnancy [26,27], and treatment for infertility [26]. However, the only factor consistently associated with increased HB risk is low weight at birth [5] and prematurity [23] followed by tobacco consumption during pregnancy; the two latter may also be related to low weigh at birth [5].…”

“…HB is the most common type, representing approximately 1% of all cancers in this age group [4]. According to a US study [5] carried out between 2002 and 2008, approximately 10 of every one million children under one year of age are affected by HB. The diagnosis is based primarily on ultrasound and CT scan following detection of an increased abdominal mass; symptoms include anorexia, weight loss and pain [6].…”

Hepatoblastoma modeling in mice places Nrf2 within a cancer field established by mutant β-catenin

“…Moreover, in contrast to young mice of the parental Albu- and Alb-c-Myc mice (lanes 2, 3, 6, 7, and 8) at P1 (n = 3), P7-P8 (n = 5), and P28 (n = 1) (lane 9) was gel-fractionated, transferred to a nylon membrane, and hybridized to a radiolabeled c-Myc-specific probe and, thereafter, a radiolabeled oligonucleotide probe specific for 18s rRNA. Endogenous c-Myc mRNA is abundantly expressed at P1 in WT and Alb-c-Myc mice (lanes 1-3) but is negligible by P7-P8 (lanes [4][5][6][7][8]. In contrast, the Albumin-c-Myc transgene is expressed by P7-P8 and continues to increase as the liver matures (lanes 6-9, bounded by box, and Supplemental min-c-Myc strain (referred to as Alb-Myc mice), which had normal body and liver weights ( Figure 1C) and livers that were biochemically and histologically normal, except for mild cellular and nuclear hypertrophy in periportal hepatocytes (Supplemental Figure 1, A and B; supplemental material available online with this article; doi:10.1172/jci.insight.88549DS1), all mice expressing mutant β-catenin displayed hepatomegaly ( Figure 1, D and E) and became moribund, requiring euthanization between 21 and 40 days of age ( Figure 1F).…”

“…Although most HBs are sporadic, multiple studies have established a linkage between HB and several familial cancer and congenital malformation syndromes (7), most notably familial adenomatous polyposis, a cancer syndrome resulting from mutations in adenomatous polyposis coli, a negative regulator of Wnt signaling. A causative role for Wnt in HB is not only suggested by the high frequency of activating mutations or deletions in CTNNB1 (8) that render the canonical Wnt effector β-catenin constitutively active for Wnt signaling due to impaired degradation of the protein (9), but also by the high frequency of HBs that display Wnt activation via an array of nonmutational mechanisms (10).…”

Hepatoblastoma Etiopathogenesis

“…Heritable predisposition to HB occurs in a small proportion of cases in patients with genetic syndromes, such as Beckwith-Wiedemann syndrome (BWS), familial adenomatous polyposis (FAP), and trisomy 18 [16]. The genetics of BWS is complex, but clearly associated with alterations in the expression or function of one or more genes in the 11p15.5 imprinted gene cluster.…”