Analysis of sequence variations in the promoter region of TFF1 and MUC1 genes in breast cancer

ABBA MC; CERMIGNANI L; ISLA-LARRAIN M; CRESPO M; COLUSSI A; ALDAZ CM; SEGAL-EIRAS A; CROCE MV

Robison College, Cambridge, UK

Workshop; 9th International Workshop on Carcinoma-associated Mucins; 2007

British Associate for Cancer Research (BACR)

The mucin 1 glycoprotein (MUC1) and trefoil factor 1 protein (TFF1) are expressed mostly on the apical membrane of various glandular epithelia such as in luminal breast epithelial cells. Up-regulated or aberrant TFF1 and MUC1 expression has been reported in various primary carcinomas as well as their associated metastases including human breast carcinoma. It was further determined that this increase in TFF1 and MUC1 expression is due mainly to transcriptional regulatory events. The aim of this study was to investigate DNA sequence variations of 5’-flanking region of TFF1 and MUC1 genes in breast cancer cells. DNAs from 110 human breast tissues and 8 breast cancer cell lines were purified and further screened for sequence variations by PCR-LIS-SSCP technique. TFF1 and MUC1 promoter polymorphisms were further characterized by PCR-RFLP and direct DNA sequencing. We identified a TFF1 single nucleotide polymorphism (assigned as A and C allelic variants) located at -29/-245 bp relative to the transcriptional start site (TSS). TFF1 promoter allelic frequencies were 0.52 and 0.48 for A and C variants respectively. We identified a statistical significant enrichment of C homozygous genotype among invasive breast carcinomas compared with normal breast tissue (p=0.035). In addition, a trend of significance was observed for the enrichment of C homozygous genotype in patients with advanced tumor stages. We identified sequences variations in the promoter region of MUC1 gene mapped at -334/-519 bp relative to the TSS. Non-statistical significant difference was detected in MUC1 promoter polymorphism and the clinicopathological variables analyzed (tumor stage, grade, estrogen receptor status, etc.). This study showed that the novel polymorphisms identified in the promoter region of the TFF1 gene may be pathologically significant in human breast cancer cells.