In conclusion, we have demonstrated that high levels of cyclin D1 protein expression are related to outcome in colorectal cancer; however, the CCND1A870G polymorphism is unrelated to either cyclin D1 protein expression or patient survival.
Over-representation of the CCND1 A allele was also seen in sporadic colorectal cancer cases compared to controls but this did not attain statistical significance (P=0.08).
Increased expression of cyclin D1, p53, Ki-67, beta-catenine and Her-2/neu, and decreased expression of p27 may be important events in the three ethnic groups with colorectal cancer.
Comparison of the CCND1G870A genotype frequencies revealed no significant associations between presence of the A allele and the risk of either breast or colorectal cancer.
Elevated beta-catenin levels in colorectal cancer result in the binding of beta-catenin to LEF-1 and increased transcriptional activation of the CCND1 gene.
In all cohorts combined, the CCND1 polymorphism did not show statistically significant associations to risk of colorectal cancer (odds ratio (OR) for A allele carriers, 1.04; 95% confidence interval (95% CI), 0.82-1.32) or adenoma (OR, 0.96; 95% CI, 0.79-1.18).
The effect of the cyclin D1 (CCND1) A870G polymorphism on colorectal cancer risk is modified by glutathione-S-transferase polymorphisms and isothiocyanate intake in the Singapore Chinese Health Study.
This investigation was designed to evaluate the effect of cyclin D1 gene polymorphism on the risk of colorectal cancer in Chinese migrants of the Taiwanese population.
In multivariate analysis, AURKA was associated with cyclin D1 expression (P = .010) and inversely with PIK3CA mutation (P=.014), fatty acid synthase expression (P=.028), and family history of colorectal cancer (P = .050), but not with sex, age, body mass index, tumor location, stage, CIMP, MSI, KRAS, BRAF, BMI, LINE-1 hypomethylation, p53, p21, beta-catenin, or cyclooxygenase 2.
In multivariate logistic regression analysis, the associations of JCVT with p53 [adjusted odds ratio (OR), 8.45; P < .0001], CIN (adjusted OR, 2.53; P = .003), cyclin D1 (adjusted OR, 1.57; P = .02), LINE-1 hypomethylation (adjusted OR, 1.97 for a 30% decline as a unit; P = .03), BRAF mutation (adjusted OR, 2.20; P = .04), and family history of colorectal cancer (adjusted OR, 0.64; P = .04) remained statistically significant.
Women homozygous for the cyclin D1 870 GG genotype showed an increased risk for developing colorectal cancer compared to those with the AG+AA genotypes and this result was statistically significant (OR 5.568, 95% CI 1.270-24.417, p=0.02).
We conclude that rare variants of CCND1 are risk factors for colorectal cancer, with considerably larger effects than common polymorphisms, and as such should be systematically evaluated in susceptibility studies.