Effect of cyclin D1 (CCND1) polymorphism on gastric premalignant condition

Background: Cyclin D1 (CCND1) is known to regulate function in G1 arrest and therefore may play an important role in carcinogenesis. The aim of this study was to investigate the effect of G870A polymorphism of the CCND1 gene on gastric precancerous condition, on histological chronic gastritis, and on the risk of peptic ulcer diseases. Methods: Restriction fragment length polymorphism analysis was performed for polymorphisms at 870GA in the CCND1 gene in 524 cancer-free subjects, including 111 gastric and 54 duodenal ulcers, and 359 non-ulcer subjects. Gastritis scores of antral gastric mucosa were assessed according to the updated Sydney system in 384 subjects. Results: CCND1 genotype was significantly associated with the severity of intestinal metaplasia by the Kruskal-Wallis test, and this tendency was especially stronger among older subjects of 61 years or older (overall subjects: p=0.035, 61 years∼: p=0.007). We also found that the 870AA genotype held a significant high risk of intestinal metaplasia [Helicobacter pylori infection adjusted odds ratio (OR)=1.8, 95% confidence interval (CI)=1.03-3.15, p=0.04]. The same genotype was more closely associated with the risk of intestinal metaplasia in older subjects of 61 years or older (H. pylori infection adjusted OR=3.45, 95% CI=1.48-8.08, p=0.004). A non-significant association was found between CCND1 G870A genotypes and the risk of peptic ulcer diseases as well as histological severity of acute or chronic inflammation. Conclusions: It appears that the G870A polymorphism of CCND1 is associated with gastric premalignant condition especially in older subjects.