Cropp Cheryl D, Robbins Christiane M, Sheng Xin, Hennis Anselm J M, Carpten John D, Waterman Lyndon, Worrell Ronald, Schwantes-An Tae-Hwi, Trent Jeffrey M, Haiman Christopher A, Leske M Cristina, Wu Suh-Yuh, Bailey-Wilson Joan E, Nemesure Barbara
Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland.
Prostate. 2014 Dec;74(16):1579-88. doi: 10.1002/pros.22871. Epub 2014 Sep 22.
African American men (AA) exhibit a disproportionate share of prostate cancer (PRCA) incidence, morbidity, and mortality. Several genetic association studies have implicated select 8q24 loci in PRCA risk in AA. The objective of this investigation is to evaluate the association between previously reported 8q24 risk alleles and PRCA in African-Barbadian (AB) men known to have high rates of PRCA.
Ten previously reported candidate tag SNPs were genotyped and/or imputed in the 8q24 region in 532 AB men with PRCA and 513 AB controls from the Prostate Cancer in a Black Population (PCBP) study.
Rs2124036 was significant in AB men, (OR = 2.7, 95% CI (1.3-5.3), P = 0.005, Empirical (max (T), corrected for multiple testing) P = 0.03) for the homozygous C/C genotype. Only a single SNP from this region remained statistically significant in our analysis of our AB population. These results may indicate the presence of a founder effect or due to the chosen SNPs not tagging an ancestral haplotype bearing the 8q24 risk allele(s) in this population or could reflect inadequate power to detect an association. We conducted a meta-analysis including our AB population along with two additional African Caribbean populations from Tobago and Jamaica for SNPs rs16901979 and rs1447295. Meta-analysis results were most significant for rs16901979 A allele (Z score 2.73; P = 0.006) with a summary OR = 1.31 (95% CI: 1.09-1.58).
Additional studies are needed to provide deeper genotype coverage to further interrogate the 8q24 region to understand its contribution to PRCA in this population.
非裔美国男性(AA)在前列腺癌(PRCA)的发病率、患病率和死亡率方面所占比例过高。多项基因关联研究表明,特定的8q24基因座与AA人群患PRCA的风险有关。本研究的目的是评估先前报道的8q24风险等位基因与已知PRCA发病率较高的非洲巴巴多斯(AB)男性患PRCA之间的关联。
在一项针对黑人人群前列腺癌(PCBP)的研究中,对532名患有PRCA的AB男性和513名AB对照者的8q24区域中的10个先前报道的候选标签单核苷酸多态性(SNP)进行基因分型和/或推算。
对于纯合C/C基因型,rs2124036在AB男性中具有显著性(比值比[OR]=2.7,95%置信区间[CI](1.3 - 5.3),P = 0.005,经多次检验校正后的经验性(最大T值)P = 0.03)。在我们对AB人群的分析中,该区域只有一个SNP仍具有统计学显著性。这些结果可能表明存在奠基者效应,或者是由于所选的SNP未标记该人群中携带8q24风险等位基因的祖先单倍型,也可能反映出检测关联的能力不足。我们对rs16901979和rs1447295这两个SNP进行了荟萃分析,纳入了我们的AB人群以及另外两个来自多巴哥和牙买加的非洲加勒比人群。rs16901979 A等位基因的荟萃分析结果最为显著(Z值为2.73;P = 0.006),汇总OR = 1.31(95% CI:1.09 - 1.58)。
需要进一步开展研究,以提供更深入的基因型覆盖范围,从而进一步探究8q24区域,以了解其在该人群中对PRCA的影响。