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).
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).
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.
MiR-519d negatively regulated the expression of CCND1 via directly bound to CCND1 3`UTR. si-CCND1 could downregulate the CCND1 expression in colorectal cancer HCT116 and SW480 cells. si-CCND1 increased the sensitivity of colorectal cancer cells to 5-Fu.
These findings support the concept that the cell cycle regulation may play a role in colorectal cancer initiation and development and CCND1A870G genotyping maybe a feasible technology for colorectal cancer early detection.
The present study was designated to clarify whether common single nucleotide polymorphisms (SNPs) of the transcription factor 7- like 2 (TCF7L2) and cyclin D1 (CCND1) genes are associated with colorectal cancer risk in Mexican patients.
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.
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 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.
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.
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.
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.