Absence of association between cyclin D1 (CCND1) G870A polymorphism and age of onset in hereditary nonpolyposis colorectal cancer

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • The German HNPCC-Consortium - (Autor:in)
  • Stefan Krüger - , Abteilung Chirurgische Forschung (Autor:in)
  • Andrea Bier - , Institut für Klinische Genetik (Autor:in)
  • Jens Plaschke - , Abteilung Chirurgische Forschung (Autor:in)
  • Hans K. Schackert - , Abteilung Chirurgische Forschung (Autor:in)

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)191-197
Seitenumfang7
FachzeitschriftCancer letters
Jahrgang236
Ausgabenummer2
PublikationsstatusVeröffentlicht - 18 Mai 2006
Peer-Review-StatusJa

Externe IDs

PubMed 16832876

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete

Schlagwörter

  • Age of Onset, AO, Cyclin D1, CCND1, Genetic modifier, Hereditary nonpolyposis colorectal cancer, HNPCC, Polymorphism G870A