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.
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Abbreviations
- BMI:
-
Body mass index
- ALCAM:
-
Activated leukocyte cell adhesion molecule
- CI:
-
Confidence interval
- OR:
-
Odds ratio
- SNP:
-
Single nucleotide polymorphism
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Acknowledgments
This study was supported by a Young Scientists fund of the Third Affiliated Hospital to Nantong University (SYQNJJ10001), the Medical Technology Development Fund of the Hospital Administration Center in Wuxi (YGM1014), and Science Foundation of Health Bureau of Wuxi (XM1010).
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Zhou, P., Du, LF., Lv, GQ. et al. Functional polymorphisms in CD166/ALCAM gene associated with increased risk for breast cancer in a Chinese population. Breast Cancer Res Treat 128, 527–534 (2011). https://doi.org/10.1007/s10549-011-1365-x
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DOI: https://doi.org/10.1007/s10549-011-1365-x