Functional polymorphisms in CD166/ALCAM gene associated with increased risk for breast cancer in a Chinese population.

ABSTRACT

Activated Leukocyte Cell Adhesion Molecules (ALCAM, also called CD166, MEMD) are cell surface immunoglobulins that are considered to be prognostic markers for breast cancer. CD166/ALCAM has gained increasing attention because of its significant association with tumor progression and the metastatic spread of breast cancer. Two polymorphisms have been identified in the CD166/ALCAM gene 5'UTR C/T (rs6437585) and 3'UTR A/G (rs11559013). We analyzed the genotypes of 1033 individuals with breast cancer, and 1116 controls; odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. The effects and functions of polymorphisms were examined using luciferase gene expression assays and real-time PCR analyses. Our data demonstrated that individuals with the rs6437585 CT + TT genotype had an OR of 1.38 (95% CI, 1.11-1.72) for developing breast cancer, compared to those with the CC genotype. The T allele increased the risk of breast cancer in a dose-dependent manner (P (trend) < 0.001). However, there were no significant differences found between cases and controls at the rs11559013 A/G site. Additional experiments that we performed, which focused on reporter gene expression driven by CD166/ALCAM promoters, demonstrated that the presence of an rs6437585 T allele led to greater transcriptional activity than the rs6437585 C allele. This was consistent with the increased cancer risk that we observed in our case-control analysis.