E-cadherin polymorphisms and haplotypes influence risk for prostate cancer

Area of Science:

• Genetics and Cancer Research
• Molecular Biology
• Epidemiology

Background:

• The E-cadherin (CDH1) gene is linked to prostate cancer (PCA) risk, but the mechanism remains unclear.
• Specific CDH1 promoter polymorphisms, like the -160C/A variant, are associated with cancer risk, particularly in European populations.

Purpose of the Study:

• To investigate the role of CDH1 gene polymorphisms in prostate cancer susceptibility across diverse ethnic groups.
• To identify specific CDH1 variants and haplotypes associated with PCA risk.

Main Methods:

• Screened CDH1 coding and promoter regions for polymorphisms in African Americans using dHPLC.
• Conducted a genetic association study of four CDH1 polymorphisms, including -160C/A, in PCA cases and controls from African American, Jamaican, and European American populations.

Main Results:

• The -160A allele was more frequent in European American PCA patients (27.5%) than controls (19.7%).
• European American men under 65 with the -160A allele had over three times increased PCA risk (P=0.05).
• The AACT haplotype, including the -160A allele, was significantly associated with PCA in European Americans (P=0.04).

Conclusions:

• CDH1 appears to be a low-penetrant susceptibility gene for prostate cancer.
• Population-specific linkage disequilibrium patterns within the CDH1 gene may affect the influence of susceptibility alleles like -160A on PCA risk.