E-cadherin polymorphisms and haplotypes influence risk for prostate cancer

Carolina Bonilla, Tshela Mason, Layron Long, Chiledum Ahaghotu, Weidong Chen, Aiqiu Zhao, Aoua Coulibaly, Frankly Bennett, William Aiken, Trevor Tullock, Kathleen Coard, Vincent Freeman, Rick A Kittles

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

BACKGROUND. The E-cadherin (CDH1) gene has been implicated in prostate cancer (PCA) risk, however, the exact mechanism is unknown. Several polymorphisms, such as the C/A variant -160 base pairs from the transcription start site, in the CDH1 gene promoter region have been associated with cancer risk, mainly in European descent populations. METHODS. We screened the entire coding region and 3.0 kilobases of the CDH1 promoter for polymorphisms in 48 African Americans using dHPLC. Twenty-one (21) polymorphisms were observed. Four polymorphisms, including -160C/A, were genotyped in a genetic association study using incident PCA cases (N = 427) and unaffected controls (N = 337) of similar age from three different ethnic groups consisting of African Americans, Jamaicans, and European Americans. RESULTS. We observed a significantly higher frequency of the -160A allele among European American PCA patients (27.5%) compared to the control group (19.7%) (P = 0.04). More importantly, among men of European ancestry under the age of 65 who possess the -160 A allele there was over three times increased risk for prostate cancer (P = 0.05). Also, the AACT haplotype bearing the -160A allele was significantly associated with PCA in European Americans (P = 0.04). CONCLUSIONS. Our data indicate that CDH1 likely is a low-penetrant PCA susceptibility gene, however, population differences in linkage disequilibrium within the CDH1 gene region may influence the effect of susceptibility alleles such as - 160A.

Original languageEnglish (US)
Pages (from-to)546-556
Number of pages11
JournalProstate
Volume66
Issue number5
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

Fingerprint

Cadherins
Haplotypes
Prostatic Neoplasms
Alleles
African Americans
Genes
Neoplasm Genes
Transcription Initiation Site
Linkage Disequilibrium
Genetic Association Studies
Ethnic Groups
Genetic Promoter Regions
Gene Frequency
Base Pairing
Population
Control Groups
Neoplasms

Keywords

  • African Americans
  • CDH1
  • Haplotypes
  • Prostate cancer
  • Single nucleotide polymorphisms (SNP)
  • Tumor suppressor

ASJC Scopus subject areas

  • Urology

Cite this

Bonilla, C., Mason, T., Long, L., Ahaghotu, C., Chen, W., Zhao, A., ... Kittles, R. A. (2006). E-cadherin polymorphisms and haplotypes influence risk for prostate cancer. Prostate, 66(5), 546-556. https://doi.org/10.1002/pros.20374

E-cadherin polymorphisms and haplotypes influence risk for prostate cancer. / Bonilla, Carolina; Mason, Tshela; Long, Layron; Ahaghotu, Chiledum; Chen, Weidong; Zhao, Aiqiu; Coulibaly, Aoua; Bennett, Frankly; Aiken, William; Tullock, Trevor; Coard, Kathleen; Freeman, Vincent; Kittles, Rick A.

In: Prostate, Vol. 66, No. 5, 01.04.2006, p. 546-556.

Research output: Contribution to journalArticle

Bonilla, C, Mason, T, Long, L, Ahaghotu, C, Chen, W, Zhao, A, Coulibaly, A, Bennett, F, Aiken, W, Tullock, T, Coard, K, Freeman, V & Kittles, RA 2006, 'E-cadherin polymorphisms and haplotypes influence risk for prostate cancer', Prostate, vol. 66, no. 5, pp. 546-556. https://doi.org/10.1002/pros.20374
Bonilla C, Mason T, Long L, Ahaghotu C, Chen W, Zhao A et al. E-cadherin polymorphisms and haplotypes influence risk for prostate cancer. Prostate. 2006 Apr 1;66(5):546-556. https://doi.org/10.1002/pros.20374
Bonilla, Carolina ; Mason, Tshela ; Long, Layron ; Ahaghotu, Chiledum ; Chen, Weidong ; Zhao, Aiqiu ; Coulibaly, Aoua ; Bennett, Frankly ; Aiken, William ; Tullock, Trevor ; Coard, Kathleen ; Freeman, Vincent ; Kittles, Rick A. / E-cadherin polymorphisms and haplotypes influence risk for prostate cancer. In: Prostate. 2006 ; Vol. 66, No. 5. pp. 546-556.
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abstract = "BACKGROUND. The E-cadherin (CDH1) gene has been implicated in prostate cancer (PCA) risk, however, the exact mechanism is unknown. Several polymorphisms, such as the C/A variant -160 base pairs from the transcription start site, in the CDH1 gene promoter region have been associated with cancer risk, mainly in European descent populations. METHODS. We screened the entire coding region and 3.0 kilobases of the CDH1 promoter for polymorphisms in 48 African Americans using dHPLC. Twenty-one (21) polymorphisms were observed. Four polymorphisms, including -160C/A, were genotyped in a genetic association study using incident PCA cases (N = 427) and unaffected controls (N = 337) of similar age from three different ethnic groups consisting of African Americans, Jamaicans, and European Americans. RESULTS. We observed a significantly higher frequency of the -160A allele among European American PCA patients (27.5{\%}) compared to the control group (19.7{\%}) (P = 0.04). More importantly, among men of European ancestry under the age of 65 who possess the -160 A allele there was over three times increased risk for prostate cancer (P = 0.05). Also, the AACT haplotype bearing the -160A allele was significantly associated with PCA in European Americans (P = 0.04). CONCLUSIONS. Our data indicate that CDH1 likely is a low-penetrant PCA susceptibility gene, however, population differences in linkage disequilibrium within the CDH1 gene region may influence the effect of susceptibility alleles such as - 160A.",
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AU - Bonilla, Carolina

AU - Mason, Tshela

AU - Long, Layron

AU - Ahaghotu, Chiledum

AU - Chen, Weidong

AU - Zhao, Aiqiu

AU - Coulibaly, Aoua

AU - Bennett, Frankly

AU - Aiken, William

AU - Tullock, Trevor

AU - Coard, Kathleen

AU - Freeman, Vincent

AU - Kittles, Rick A

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N2 - BACKGROUND. The E-cadherin (CDH1) gene has been implicated in prostate cancer (PCA) risk, however, the exact mechanism is unknown. Several polymorphisms, such as the C/A variant -160 base pairs from the transcription start site, in the CDH1 gene promoter region have been associated with cancer risk, mainly in European descent populations. METHODS. We screened the entire coding region and 3.0 kilobases of the CDH1 promoter for polymorphisms in 48 African Americans using dHPLC. Twenty-one (21) polymorphisms were observed. Four polymorphisms, including -160C/A, were genotyped in a genetic association study using incident PCA cases (N = 427) and unaffected controls (N = 337) of similar age from three different ethnic groups consisting of African Americans, Jamaicans, and European Americans. RESULTS. We observed a significantly higher frequency of the -160A allele among European American PCA patients (27.5%) compared to the control group (19.7%) (P = 0.04). More importantly, among men of European ancestry under the age of 65 who possess the -160 A allele there was over three times increased risk for prostate cancer (P = 0.05). Also, the AACT haplotype bearing the -160A allele was significantly associated with PCA in European Americans (P = 0.04). CONCLUSIONS. Our data indicate that CDH1 likely is a low-penetrant PCA susceptibility gene, however, population differences in linkage disequilibrium within the CDH1 gene region may influence the effect of susceptibility alleles such as - 160A.

AB - BACKGROUND. The E-cadherin (CDH1) gene has been implicated in prostate cancer (PCA) risk, however, the exact mechanism is unknown. Several polymorphisms, such as the C/A variant -160 base pairs from the transcription start site, in the CDH1 gene promoter region have been associated with cancer risk, mainly in European descent populations. METHODS. We screened the entire coding region and 3.0 kilobases of the CDH1 promoter for polymorphisms in 48 African Americans using dHPLC. Twenty-one (21) polymorphisms were observed. Four polymorphisms, including -160C/A, were genotyped in a genetic association study using incident PCA cases (N = 427) and unaffected controls (N = 337) of similar age from three different ethnic groups consisting of African Americans, Jamaicans, and European Americans. RESULTS. We observed a significantly higher frequency of the -160A allele among European American PCA patients (27.5%) compared to the control group (19.7%) (P = 0.04). More importantly, among men of European ancestry under the age of 65 who possess the -160 A allele there was over three times increased risk for prostate cancer (P = 0.05). Also, the AACT haplotype bearing the -160A allele was significantly associated with PCA in European Americans (P = 0.04). CONCLUSIONS. Our data indicate that CDH1 likely is a low-penetrant PCA susceptibility gene, however, population differences in linkage disequilibrium within the CDH1 gene region may influence the effect of susceptibility alleles such as - 160A.

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