title: 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.
authors.affiliation: Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Govatati
authors.forename: Gopi Krishna
authors.initials: GK
authors.lastname: Singamsetty
authors.forename: Nayudu
authors.initials: N
authors.lastname: Nallabelli
authors.forename: Sravanthi
authors.initials: S
authors.lastname: Malempati
authors.forename: Pasupuleti Sreenivasa
authors.initials: PS
authors.lastname: Rao
authors.forename: Venkata Kranthi Kumar
authors.initials: VK
authors.lastname: Madamchetty
authors.forename: Sowdamani
authors.initials: S
authors.lastname: Govatati
authors.forename: Rudramadevi
authors.initials: R
authors.lastname: Kanapuram
authors.forename: Nagesh
authors.initials: N
authors.lastname: Narayana
authors.forename: Manjula
authors.initials: M
authors.lastname: Bhanoori
authors.forename: Kondaiah
authors.initials: K
authors.lastname: Kassetty
authors.forename: Varadacharyulu
authors.initials: V
authors.lastname: Nallanchakravarthula
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D015820:Cadherins; D019938:Cyclin D1