title: ICAM gene cluster SNPs and prostate cancer risk in African Americans.
abstract: Intercellular adhesion molecules (ICAMs) are known to be involved in various human cancers. An ICAM gene cluster lying within a 26 kb region on chromosome 19p13.2, and containing ICAM1, ICAM4, and ICAM5 has recently been identified as harboring a breast and prostate cancer susceptibility locus in two populations of European ancestry from Germany and Australia. The objective of this study was to confirm the ICAM association with prostate cancer in a sample of African American prostate cancer cases (N = 286) and controls (N = 391). Six single nucleotide polymorphisms (SNPs) within the three ICAM genes were genotyped. To control for potential population stratification an ancestry-adjusted association analysis was performed. We found that ICAM1 SNPs, -9A/C (rs5490) and K469E (rs5498) were associated with prostate cancer risk in men with a family history of prostate cancer (P = 0.008). Specifically, increased risk was observed for individuals who possessed the CC genotype of the -9 A/C variant (odds ratio = 2.5; 95% CI = 1.0-6.3) and at least one G allele of non-synonymous K469E variant (odds ratio = 1.8; 95% CI = 1.2-3.1). Strong linkage disequilibrium was observed across the ICAM region (P < 0.001). A common haplotype within the ICAM gene cluster, harboring the -9A/C variant was significantly associated with prostate cancer (P = 0.03), mainly due to men with family history (P = 0.01). Our results replicate previous findings of association of the ICAM gene cluster with prostate cancer and suggest that common genetic variation within ICAM1 and not ICAM5 may be an important risk factor for prostate cancer.
authors.affiliation: Human Cancer Genetics, Comprehensive Cancer Center, The Ohio State University, 494 Tzagournis Medical Research Facility, 420 W. 12th Avenue, Columbus, OH 43210, USA.
authors.forename: Hankui
authors.initials: H
authors.lastname: Chen
authors.forename: Wenndy
authors.initials: W
authors.lastname: Hernandez
authors.forename: Mark D
authors.initials: MD
authors.lastname: Shriver
authors.forename: Chiledum A
authors.initials: CA
authors.lastname: Ahaghotu
authors.forename: Rick A
authors.initials: RA
authors.lastname: Kittles
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D015815:Cell Adhesion Molecules / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015815:Cell Adhesion Molecules; C095100:ICAM4 protein, human; C086747:ICAM5 protein, human; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018799:Intercellular Adhesion Molecule-1; D017430:Prostate-Specific Antigen