title: CCND1 polymorphism and age of onset of hepatoblastoma.
abstract: Cyclin D1, encoded by the gene CCND1, is a major regulator of the cell cycle transition from G1 phase to S phase. A CCND1 polymorphism (G to A) at codon 242, the boundary of exon 4 and intron 4, affects splicing such that exon 5 is not expressed in the A allele. Since exon 5 is involved in rapid turnover, the variant cyclin D1 corresponding to the A allele may have a longer half-life. A previous study demonstrated that in families with hereditary nonpolyposis colorectal cancer, the age of onset of colorectal cancer varied according to variation at this polymorphic site. We examined this CCND1polymorphism in a series hepatoblastoma, a childhood liver cancer that shares other molecular features with colon cancer. We determined in an analysis of 84 children with hepatoblastoma that the G/A exon 4 polymorphism in CCND1 is correlated with the age of onset of hepatoblastomas. The A/A genotype is associated with an earlier age of onset compared to the G/A or G/G genotype. The median age of patients with the G/G genotype was 22 months, compared to 17 months in patients with the G/A genotype and 11 months for the A/A genotype. These findings suggest that the CCND1 A polymorphism may contribute to tumor development in children with hepatoblastoma.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-8593, USA.
authors.forename: Samart
authors.initials: S
authors.lastname: Pakakasama
authors.forename: Tina T-L
authors.initials: TT
authors.lastname: Chen
authors.forename: William
authors.initials: W
authors.lastname: Frawley
authors.forename: Carolyn Y
authors.initials: CY
authors.lastname: Muller
authors.forename: Edwin C
authors.initials: EC
authors.lastname: Douglass
authors.forename: Roger
authors.initials: R
authors.lastname: Lee
authors.forename: Brad H
authors.initials: BH
authors.lastname: Pollock
authors.forename: Gail E
authors.initials: GE
authors.lastname: Tomlinson
mesh_terms: D017677:Age Distribution; D017668:Age of Onset; D044383:Black People; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D018197:Hepatoblastoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006630:Hispanic or Latino; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D044465:White People
chemical_list: D019938:Cyclin D1; D004247:DNA