Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer.
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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2002
|
| _version_ | 1797089898244603904 |
|---|---|
| author | Porter, T Richards, F Houlston, R Evans, D Jankowski, J Macdonald, F Norbury, G Payne, S Fisher, SA Tomlinson, I Maher, E |
| author_facet | Porter, T Richards, F Houlston, R Evans, D Jankowski, J Macdonald, F Norbury, G Payne, S Fisher, SA Tomlinson, I Maher, E |
| author_sort | Porter, T |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:10:38Z |
| format | Journal article |
| id | oxford-uuid:b4141b0b-6702-424d-80ff-a8d6b4adf85d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:10:38Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:b4141b0b-6702-424d-80ff-a8d6b4adf85d2022-03-27T04:23:36ZContribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b4141b0b-6702-424d-80ff-a8d6b4adf85dEnglishSymplectic Elements at Oxford2002Porter, TRichards, FHoulston, REvans, DJankowski, JMacdonald, FNorbury, GPayne, SFisher, SATomlinson, IMaher, EThe 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. |
| spellingShingle | Porter, T Richards, F Houlston, R Evans, D Jankowski, J Macdonald, F Norbury, G Payne, S Fisher, SA Tomlinson, I Maher, E Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer. |
| title | Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer. |
| title_full | Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer. |
| title_fullStr | Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer. |
| title_full_unstemmed | Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer. |
| title_short | Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer. |
| title_sort | contribution of cyclin d1 ccnd1 and e cadherin cdh1 polymorphisms to familial and sporadic colorectal cancer |
| work_keys_str_mv | AT portert contributionofcyclind1ccnd1andecadherincdh1polymorphismstofamilialandsporadiccolorectalcancer AT richardsf contributionofcyclind1ccnd1andecadherincdh1polymorphismstofamilialandsporadiccolorectalcancer AT houlstonr contributionofcyclind1ccnd1andecadherincdh1polymorphismstofamilialandsporadiccolorectalcancer AT evansd contributionofcyclind1ccnd1andecadherincdh1polymorphismstofamilialandsporadiccolorectalcancer AT jankowskij contributionofcyclind1ccnd1andecadherincdh1polymorphismstofamilialandsporadiccolorectalcancer AT macdonaldf contributionofcyclind1ccnd1andecadherincdh1polymorphismstofamilialandsporadiccolorectalcancer AT norburyg contributionofcyclind1ccnd1andecadherincdh1polymorphismstofamilialandsporadiccolorectalcancer AT paynes contributionofcyclind1ccnd1andecadherincdh1polymorphismstofamilialandsporadiccolorectalcancer AT fishersa contributionofcyclind1ccnd1andecadherincdh1polymorphismstofamilialandsporadiccolorectalcancer AT tomlinsoni contributionofcyclind1ccnd1andecadherincdh1polymorphismstofamilialandsporadiccolorectalcancer AT mahere contributionofcyclind1ccnd1andecadherincdh1polymorphismstofamilialandsporadiccolorectalcancer |