title: 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.
authors.affiliation: Department of Intensive Care Unite, The Third Affiliated Hospital to Nantong University, 585 Xing Yuan North Road, 214041 Wuxi, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Liang-Feng
authors.initials: LF
authors.lastname: Du
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Lv
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Yu
authors.forename: Yuan-Long
authors.initials: YL
authors.lastname: Gu
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Li
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics* / Q000556:secondary; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002681:China / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005326:Fetal Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; D004273:DNA, Neoplasm; D005326:Fetal Proteins; D008156:Luciferases; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule