Chen Hankui, Hernandez Wenndy, Shriver Mark D, Ahaghotu Chiledum A, Kittles Rick A
Human Cancer Genetics, Comprehensive Cancer Center, The Ohio State University, 494 Tzagournis Medical Research Facility, 420 W. 12th Avenue, Columbus, OH 43210, USA.
Hum Genet. 2006 Aug;120(1):69-76. doi: 10.1007/s00439-006-0184-3. Epub 2006 May 30.
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.
已知细胞间黏附分子（ICAMs）与多种人类癌症有关。位于19号染色体p13.2区域26 kb范围内、包含ICAM1、ICAM4和ICAM5的一个ICAM基因簇，最近在来自德国和澳大利亚的两个欧洲血统人群中被确定为含有乳腺癌和前列腺癌易感基因座。本研究的目的是在非裔美国前列腺癌病例样本（N = 286）和对照样本（N = 391）中确认ICAM与前列腺癌的关联。对三个ICAM基因中的六个单核苷酸多态性（SNP）进行了基因分型。为控制潜在的群体分层，进行了祖先调整后的关联分析。我们发现，ICAM1的SNP，-9A/C（rs5490）和K469E（rs5498）与有前列腺癌家族史的男性患前列腺癌的风险相关（P = 0.008）。具体而言，对于具有-9 A/C变体CC基因型的个体（优势比 = 2.5；95%置信区间 = 1.0 - 6.3）和非同义K469E变体的至少一个G等位基因的个体（优势比 = 1.8；95%置信区间 = 1.2 - 3.1），观察到风险增加。在整个ICAM区域观察到强连锁不平衡（P < 0.001）。ICAM基因簇内一个包含-9A/C变体的常见单倍型与前列腺癌显著相关（P = 0.03），主要是由于有家族史的男性（P = 0.01）。我们的结果重复了之前关于ICAM基因簇与前列腺癌关联的发现，并表明ICAM1而非ICAM5内的常见基因变异可能是前列腺癌的一个重要风险因素。
