title: Absence of association between cyclin D1 (CCND1) G870A polymorphism and age of onset in hereditary nonpolyposis colorectal cancer.
abstract: CCND1 encodes cyclin D1, which plays an important role in the G1 to S phase transition of the cell cycle. A common polymorphism (c.G870A) increases alternate splicing. Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in mismatch repair (MMR) genes, mainly MSH2 and MLH1, and shows a wide range in the age of its onset (AO), suggesting the existence of other modifying genetic factors. To date, two studies have investigated the association between CCND1 G/A variation and AO in HNPCC with contradictory results in 86 and 146 MMR mutation carriers, respectively. To clarify the role of the CCND1 G/A variation in HNPCC, we performed a study in 406 individuals carrying exclusively clear cut pathogenic mutations in MSH2 or MLH1. We did not observe a significant difference in genotype frequencies of affected and unaffected mutation carriers and healthy controls. A significant association between CCND1 genotypes and AO was found neither in the global comparison (log-rank, P = 0.2981; Wilcoxon, P = 0.2567) nor in a multivariate Cox regression analysis (hazard ratios 1.111, 95%CI 0.950-1.299, P = 0.188 and 1.090, 95%CI 0.868-1.369, P = 0.459 for the additive and dominant effect, respectively). We conclude, that the CCND1 G870A sequence variation is not a genetic modifier of the phenotype of HNPCC.
authors.affiliation: Department of Surgical Research, Dresden University of Technology, Fetscherstr. 74, D-01307 Dresden, Germany. stefan.krueger@mailbox.tu-dresden.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Krüger
authors.forename: Christoph
authors.initials: C
authors.lastname: Engel
authors.forename: Andrea
authors.initials: A
authors.lastname: Bier
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
authors.forename: Constanze
authors.initials: C
authors.lastname: Pagenstecher
authors.forename: Magnus von Knebel
authors.initials: Mv
authors.lastname: Doeberitz
authors.forename: Elke
authors.initials: E
authors.lastname: Holinski-Feder
authors.forename: Gabriela
authors.initials: G
authors.lastname: Moeslein
authors.forename: Gisela
authors.initials: G
authors.lastname: Keller
authors.forename: Erdmute
authors.initials: E
authors.lastname: Kunstmann
authors.forename: Waltraut
authors.initials: W
authors.lastname: Friedl
authors.forename: Jens
authors.initials: J
authors.lastname: Plaschke
authors.forename: Josef
authors.initials: J
authors.lastname: Rüschoff
authors.forename: Hans K
authors.initials: HK
authors.lastname: Schackert
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D019938:Cyclin D1