TY - JOUR
T1 - Absence of association between cyclin D1 (CCND1) G870A polymorphism and age of onset in hereditary nonpolyposis colorectal cancer
AU - Krüger, Stefan
AU - Engel, Christoph
AU - Bier, Andrea
AU - Mangold, Elisabeth
AU - Pagenstecher, Constanze
AU - von Knebel Doeberitz, Magnus
AU - Holinski-Feder, Elke
AU - Moeslein, Gabriela
AU - Keller, Gisela
AU - Kunstmann, Erdmute
AU - Friedl, Waltraut
AU - Plaschke, Jens
AU - Rüschoff, Josef
AU - Schackert, Hans K.
AU - The German HNPCC-Consortium, German HNPCC-Consortium
N1 - Funding Information:
We thank Mr A Schiewart for excellent technical assistance. This work was supported by the Verbundprojekt ‘Familiärer Darmkrebs’ of the Deutsche Krebshilfe (DKH, German Cancer Aid, 70–3032).
PY - 2006/5/18
Y1 - 2006/5/18
N2 - 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.
AB - 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.
KW - Age of Onset, AO
KW - Cyclin D1, CCND1
KW - Genetic modifier
KW - Hereditary nonpolyposis colorectal cancer, HNPCC
KW - Polymorphism G870A
UR - http://www.scopus.com/inward/record.url?scp=33646510881&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2005.05.013
DO - 10.1016/j.canlet.2005.05.013
M3 - Article
C2 - 16832876
AN - SCOPUS:33646510881
SN - 0304-3835
VL - 236
SP - 191
EP - 197
JO - Cancer Letters
JF - Cancer Letters
IS - 2
ER -