Contribution of cyclin D1 (CCND1) and E-cadherin (CDH1) alterations to colorectal cancer susceptibility: a case–control study

Abstract

Cyclin D1 (CCND1) and E-cadherin (CDH1) are two important genes of the β-catenin/LEF pathway that is involved in tumorigenesis of various cancers including colorectal cancer (CRC). However, studies of the association between genetic variants of these two genes and CRC have shown conflicting results. We conducted a genetic association study in South Indian population (cases, 103; controls, 107) to assess the association of CCND1 870G/A and CDH1 -160C/A single nucleotide polymorphisms (SNPs) with CRC risk. Genotyping of SNPs was performed by PCR sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software. In addition, to better understand the role of CCND1 and CDH1 in the pathophysiology of CRC, the expression pattern was evaluated in analogous tumor and adjacent normal tissues from 23 CRC patients by Western blot analysis. The frequencies of CCND1 870A/A (P = 0.045) genotype, CDH1 -160A allele (P = 0.042), and 870A/-160A haplotype (P = 0.002) were significantly higher in patients as compared with controls. Strong LD was observed between 870G/A and -160C/A SNPs in cases (D' = 0.76) as compared to controls (D' = 0.32). Furthermore, elevated CCND1 and diminished CDH1 expression was observed in tumor tissue as compared with analogous normal tissue of CRC patients. Interestingly, advanced-stage tumors showed wider expression alterations than in early-stage tumors. In conclusion, CCND1 870G/A and CDH1 -160C/A SNPs may modify the risk of CRC susceptibility in South Indian population. In addition, elevated CCND1 and diminished CDH1 expression appears to be useful prognostic markers for CRC.

Investigation of <em>cyclin D1</em> rs9344 G&gt;A polymorphism in colorectal cancer: a meta-analysis involving 13,642 subjects

“…There were 9 studies conducted in Asians,12,13,15,18,27,30,33,37 16 studies conducted in Caucasians,14–17,26,28,32,34–36,38–41 and 3 studies conducted in mixed populations 29,31,42. Of these articles, 22 investigated sCRC,12–18,26–38 and 6 investigated HNPCC 16,26,39–42. And the detailed characteristics of the included studies12–18,26–42 and the distribution of the CCND1 rs9344 G>A polymorphism as well as alleles are listed in Tables 1 and 2, respectively.…”

“…Of these articles, 22 investigated sCRC,12–18,26–38 and 6 investigated HNPCC 16,26,39–42. And the detailed characteristics of the included studies12–18,26–42 and the distribution of the CCND1 rs9344 G>A polymorphism as well as alleles are listed in Tables 1 and 2, respectively.…”

“…In total, 28 eligible studies12–18,26–42 with 5,784 CRC cases and 7,858 controls were included in our meta-analysis. Overall, the CCND1 rs9344 G>A polymorphism was associated with the overall CRC risk in four genetic models (A vs G: OR, 1.12; 95% CI: 1.03–1.21, P =0.005; AA vs GG: OR, 1.25; 95% CI: 1.06–1.48, P =0.008; AA+GA vs GG: OR, 1.18; 95% CI: 1.05–1.33, P =0.007; AA vs GA+GG: OR, 1.13; 95% CI: 1.05–1.28, P =0.042; Table 3 and Figure 2).…”

“…Of late, numerous epidemiologic investigations focused on the relationship of the CCND1 polymorphism with CRC risk 12–18,26–42. The most prevalent CCND1 gene polymer phism, rs9344 G>A, has been most widely explored.…”

Differentially Expressed Genes Extracted by the Tensor Robust Principal Component Analysis (TRPCA) Method

“…Specifically, the official name CDH1 is Cadherin 1, which was the most correlated with this dataset. Recently, works [33,34] have described mutations in CDH1 in COAD cell lines. Cytoplasmic CDH1 has independent prognostic value in PAAD and provides a new target for prognostic treatment [35].…”