title: A non-synonymous polymorphism Thr115Met in the EpCAM gene is associated with an increased risk of breast cancer in Chinese population.
abstract: As a tumor-associated antigen and a surface marker of breast cancer stem cells (BCSCs), epithelial cell adhesion molecule (EpCAM) plays an important role in not only cell adhesion, morphogenesis, metastases but also carcinogenesis. A non-synonymous C/T polymorphism (rs1126497) in exon3 of EpCAM causes a transition of 115 amino acid from Met to Thr. Another polymorphism (A/G, rs1421) in the 3'UTR causes loss of has-miR-1183 binding. A multiple independent case-control analysis was performed to assess the association between EpCAM genotypes and breast cancer risk. We observed that the variant EpCAM genotype (rs1126497 CT, and TT) was associated with substantially increased risk of breast cancer. Genotyping a total of 1643 individuals with breast cancer and 1818 control subjects in Eastern and Southern Chinese populations showed that rs1126497 CT + TT genotype had an odd ratio of 1.40 (95% confidence interval, 1.16-1.57) for developing breast cancer compared with CC genotype. The allele T increases the risk of breast cancer in a dose-dependent response manner (P (trend) < 0.001). Moreover, compared to breast cancer patients carrying the CC genotype, the EpCAM SNP rs1126497 CT or TT carrier was significantly associated with early breast cancer onset (P = 0.0023). However, no significant difference was found in genotype frequencies at the rs1421 A/G site between cases and controls. These findings suggest that M115T polymorphism in EpCAM may be a genetic modifier for developing breast cancer.
authors.affiliation: The Institute of Biology and Medical Sciences, Medical College of Soochow University, 215123, Suzhou, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Jiang
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Li
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Ping
authors.initials: P
authors.lastname: Zou
authors.forename: Yuting
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaonong
authors.initials: X
authors.lastname: Bin
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000328:Adult; D017668:Age of Onset; D000951:Antigens, Neoplasm / Q000235:genetics*; D044466:Asian People; D001483:Base Sequence; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology* / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics*; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone