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

作者：Kruger S^*; Engel C; Bier A; Mangold E; Pagenstecher C; Doeberitz MV; Holinski Feder E; Moeslein G; Keller G; Kunstmann E; Friedl W; Plaschke J; Ruschoff J; Schackert HK

来源：Cancer Letters, 2006, 236(2): 191-197.

DOI：10.1016/j.canlet.2005.05.013

• cyclin D1
• CCND1
• polymorphism G870A
• hereditary nonpolyposis colorectal cancer
• HNPCC
• age of onset
• AO
• genetic modifier

CCND1 encodes cyclin D1, which plays an important role in the G, 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.

• 出版日期2006-5-18
• 单位河北医科大学