title: Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer.
abstract: The molecular basis for most non-HNPCC familial colorectal cancer cases is unknown, but there is increasing evidence that common genetic variants may play a role. We investigated the contribution of polymorphisms in two genes implicated in the pathogenesis of colorectal cancer, cyclin D1 (CCND1) and E-cadherin (CDH1), to familial and sporadic forms of the disease. The CCND1 870A/G polymorphism is thought to affect the expression of CCND1 through mRNA splicing and has been reported to modify the penetrance of HNPCC. Inactivation of E-cadherin is common in colorectal cancer, and truncating germline mutations have been reported to confer susceptibility to colorectal as well as diffuse gastric cancer. The -160A/C CDH1 polymorphism appears to affect expression of CDH1 and may therefore also confer an increased risk. We found a significantly higher frequency of CCND1 870A allele in 206 familial cases compared to 171 controls (P=0.03). Odds ratios in heterozygotes and homozygotes were 1.7 (95% CI: 1.0-2.66) and 1.8 (95% CI: 1.0-3.3) respectively. The difference was accounted for by an over-representation of A allele in non-HNPCC familial cases (P=0.007). 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). No significant differences between the frequency of CDH1 -160A/C genotypes in familial, sporadic colorectal cancer cases and controls were seen, although a possible association between the low expressing A allele and right-sided tumours was detected in familial cases.
authors.affiliation: Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Porter
authors.forename: Frances M
authors.initials: FM
authors.lastname: Richards
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: D Gareth R
authors.initials: DG
authors.lastname: Evans
authors.forename: Janusz A
authors.initials: JA
authors.lastname: Jankowski
authors.forename: Fiona
authors.initials: F
authors.lastname: Macdonald
authors.forename: Gail
authors.initials: G
authors.lastname: Norbury
authors.forename: Stewart J
authors.initials: SJ
authors.lastname: Payne
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Fisher
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D015820:Cadherins; D017931:DNA Primers; D004273:DNA, Neoplasm; D019938:Cyclin D1