title: CYCLIN D1 as a genetic modifier in hereditary nonpolyposis colorectal cancer.
abstract: Hereditary nonpolyposis colorectal cancer is associated with inherited defects in DNA mismatch repair. Clinical variation even in cases with identical predisposing mutations suggests the existence of other factors contributing to the phenotype. We addressed the modifying role of the common A/G polymorphism in exon 4 and the alternatively spliced transcripts a and b of the CCND1 gene encoding cyclin D1 in a series of 146 affected carriers of 10 MLH1 and 3 MSH2 mutations. No correlation was observed between a particular allele (A versus G) and age at onset. However, the presence of the variant transcript b in blood/normal mucosa, by multiplex reverse transcription-PCR, was associated with a significantly lower age at onset of colon cancer as compared with individuals with transcript a only (35 versus 46 years; P = 0.02). Whereas our data do not support a modifying role of A versus G allele of CCND1, the results do suggest that the relative abundance of a and b transcripts may modify the age at onset of colon cancer in hereditary nonpolyposis colorectal cancer.
authors.affiliation: Division of Human Cancer Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bala
authors.forename: P
authors.initials: P
authors.lastname: Peltomäki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D017398:Alternative Splicing; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D019940:Genes, bcl-1 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D019938:Cyclin D1; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein