A polymorphism in the 3′UTR region of E-cadherin associates with recurrence of breast cancer

Abstract

22101 Background: Maintenance of epithelial integrity plays a major role in tumor suppression but may also be important in metastasis and recurrence of cancer. Loss of E-cadherin (CDH1) is implicated in invasive lobular carcinomas of the breast. Furthermore, a polymorphic variant in the CDH1 promoter has been reported in association studies. We investigated the association of polymorphic variants in CDH1 with recurrence of breast cancer. Methods: TaqMan allelic discrimination assays were performed on genomic DNA prepared from whole blood of breast cancer patients. Genotyping was determined for several loci in CDH1 and were linked to clinical information. Results: CDH1 genotypes for the 3’UTR Ex16+246C>T polymorphism are in Hardy-Weinberg equilibrium with frequencies of: CC 69%, CT 27%, and TT 4%. Population-specific genotype frequencies were observed. There were no frequency differences between invasive ductal and invasive lobular carcinomas, but a trend toward a 4-year earlier age of onset of the latter associated with the low frequency allele. Seventeen percent of women in this cohort recurred, nearly half representing progesterone receptor-negative (PgR−) and half progesterone receptor-positive (PgR+) breast cancers. The recurrence rate for each genotype was 14.3%, 26%, and 7.1% for CC, CT, and TT genotypes, respectively. In women without recurrence, the genotype distribution was the same for PgR+ and PgR− disease. However, in those that recur, women with the CC genotype were more likely to be PgR− OR 2.32 CI [1.13–4.77] with a p value=0.023. The converse could not be evaluated due to small numbers. Conclusions: A polymorphic variant in the 3’UTR region of CDH1 is associated with recurrence of breast cancer. This association is strongest in recurrence of progesterone receptor-negative breast cancers. Recurrence in this SNP association study may reflect the effect of progesterone on proteins in adherence junctions or desmosomes or the role of CDH1 in the beta-catenin pathway. Support was from the New Jersey Commission on Cancer Research. No significant financial relationships to disclose.