Genetic variations in nucleotide excision repair pathway genes and hepatoblastoma susceptibility.

The etiology of hepatoblastoma is largely unknown due to the rarity of this disease. Nucleotide excision repair (NER), a versatile system in repairing DNA damage, is highly implicated in carcinogenesis. However, it remains unclear whether single nucleotide polymorphisms (SNPs) of genes in the NER pathway are related to hepatoblastoma risk. A total of 313 Chinese children diagnosed with hepatoblastoma and 1446 controls were recruited from seven hospitals across China. TaqMan assay was adopted to genotype 19 SNPs in NER pathway genes including ERCC1, XPA, XPC, XPD, XPF and XPG. Of them, only two SNPs in XPC gene predisposed to hepatoblastoma risk. The XPC rs2607775 polymorphism significantly contributed to hepatoblastoma risk (dominant model: adjusted OR = 1.44, 95% CI = 1.01-2.05, P = .046). However, XPC rs1870134 conferred a significantly decreased risk of hepatoblastoma in recessive model (adjusted OR = 0.50, 95% CI = 0.26-0.98, P = .042). Stratified analysis revealed that rs2607775 CG/GG genotype, rs1870134 CC genotype and four to five risk genotypes were associated with the risk of hepatoblastoma under certain subgroups. The significant relationships were confirmed by haplotype analyses and false-positive report probability analyses. In addition, expression quantitative trait locus analysis suggested that rs2607775 G increased expression of XPC mRNA. Collectively, our discover a promising candidate XPC gene as a biomarker for the risk of hepatoblastoma.

Racial Disparities and Sociodemographic Differences in Incidence and Survival Among Pediatric Patients in the United States With Primary Liver Cancer: A Surveillance, Epidemiology, and End Results (SEER) Population Study.

BACKGROUND: Primary liver cancer, including Hepatoblastoma (HB) and hepatocellular carcinoma (HCC), in pediatric populations is often fatal. The outcomes are poor despite universal health care access in pediatric patients. AIM: We investigated the sociodemographic factors affecting outcomes in pediatric patients with primary liver cancer. MATERIALS AND METHODS: This is a large population database study of Surveillance, Epidemiology, and End Results cancer registry data from 1973 to 2011. HB and HCC were analyzed regarding age, sex, race, geographic area, and treatment-related information including survival. RESULTS: In total, 998 patients, the median age at time of diagnosis was 1 year for HB [0-19; 95% confidence interval (CI), 1.5-1.9] and 14 years for HCC (0-19; 95% CI, 12.1-13.3) (P<0.001). Overall Survival (OS) in HB was 374 months (25% failures 19) versus HCC 21 months (25% failures 5; P<0.0001). In HCC, the fibrolamellar subgroup OS was 41 months (32-.) versus 16 months (11-21) in all others [hazard ratio (HR) 2.0; P=0.005]. Diagnosis between 2000 and 2011 (HB: 25% failures not reached; HCC: 38) versus diagnosis 1973 to 1999 (HB: 374; HCC: 12) had different survival (P=0.01; HR 1.9). For HB, OS in patients with age of diagnosis under 2, 25% failures was not reached versus 374 months over the age of 2 (HR 1.7; P<0.0007). African American children with HB had OS of 67 (17-.) versus all others (25% failures 21) and 48% of African American children were diagnosed after the age of 2 versus 34% of whites (HR 1.9; P=0.01). CONCLUSIONS: Later diagnosis and decreased survival in African American children with HB warrants further research.

Perinatal risk factors for hepatoblastoma.

We confirmed the strong association of hepatoblastoma with very low birth weight (relative risk <1000 g vs >or=2000 g=25.6; 95% confidence interval: 7.70-85.0) and demonstrated independent associations with congenital abnormalities and maternal Asian race in a population-based Minnesota study that included 36 cases and 7788 controls.

Promoter hypermethylation of the RASSF1A gene predicts the poor outcome of patients with hepatoblastoma.

BACKGROUND: Despite the progress of therapy, about 25% of patients with hepatoblastoma succumb to the disease. Prognostic factors, as well as improved therapies, are needed for these patients. We investigated the incidence and clinical significance of genetic and epigenetic aberrations in hepatoblastoma. PROCEDURE: beta-catenin mutation was analyzed by sequencing and promoter hypermethylation of the RASSF1A and SFRP genes by methylation-specific PCR after bisulfate treatment of DNA samples from 39 hepatoblastomas. Association of the clinical and biological features, including sex, age of patients, stage of the disease, the histological type, and the beta-catenin and RASSF1A status with overall survival was evaluated using univariate and multivariate analysis. RESULTS: beta-catenin mutation and RASSF1A methylation were found in 22 (56.4%) and 15 (38.5%) of 39 hepatoblastomas, respectively, but SFRPs methylation was not found in any of them. RASSF1A and SFRPs were unmethylated in five adjacent normal liver tissues. Patients with a RASSF1A methylated tumor were older in age (>or=2 years, P=0.036), at more advanced stages (P=0.009), and had more frequent beta-catenin mutation (P<0.001) and poorer outcome (P<0.001) than those with a RASSF1A unmethylated tumor. While univariate analysis showed the prognostic significance of age, stage, the histological type, and the beta-catenin and RASSF1A status, multivariate analysis showed only the RASSF1A methylation status as an independent factor predicting outcome (relative risk, 10.51; 95% CI, 1.21 approximately 90.97; P=0.033). CONCLUSIONS: RASSF1A methylation may be a novel molecular-genetic marker for treatment outcome in hepatoblastoma if confirmed by studies examining a larger number of hepatoblastomas.