Multiple loci with different cancer specificities within the 8q24 gene desert
Multiple loci with different cancer specificities within the 8q24 gene desert
复制标题
DOI：
10.1093/jnci/djn190
复制
发表时间：
2008-07-02
影响因子：
10.3
通讯作者：
Dunning, Alison M.
中科院分区：
文献类型：
--
作者：
Ghoussaini, Maya;Song, Honglin;Dunning, Alison M.
最近基于全基因组关联、连锁和混合扫描分析的研究报告了 8q24 中各种遗传变异与乳腺癌、前列腺癌和结直肠癌易感性的关联。该基因座位于 1.18 Mb 区域内，该区域不包含已知基因，但在其着丝粒末端以 FAM84B 为界，在其端粒末端以 c-MYC（两个候选癌症易感基因）为界。为了研究 8q24 内特定位点与特定癌症的关联，我们对前列腺（1854 例病例受试者和 1894 例对照受试者）、乳腺癌（2270 例病例受试者和 2280 例对照受试者）、结直肠癌（2299 例病例受试者和 2284 例对照受试者）、和 卵巢癌（1975 名病例受试者和 3411 名对照受试者）癌症。该基因荒漠中的五种不同的单倍型块与不同癌症的风险具体相关。其中一个区块仅与乳腺癌风险相关，另外三个区块仅与前列腺癌风险相关，第五个区块与前列腺癌、结直肠癌和卵巢癌风险相关，但与乳腺癌风险无关。我们得出的结论是，该区域至少有五个独立的功能变体。
Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with susceptibility to breast, prostate, and colorectal cancer. This locus lies within a 1.18-Mb region that contains no known genes but is bounded at its centromeric end by FAM84B and at its telomeric end by c-MYC, two candidate cancer susceptibility genes. To investigate the associations of specific loci within 8q24 with specific cancers, we genotyped the nine previously reported cancer-associated single-nucleotide polymorphisms across the region in four case-control sets of prostate (1854 case subjects and 1894 control subjects), breast (2270 case subjects and 2280 control subjects), colorectal (2299 case subjects and 2284 control subjects), and ovarian (1975 case subjects and 3411 control subjects) cancer. Five different haplotype blocks within this gene desert were specifically associated with risks of different cancers. One block was solely associated with risk of breast cancer, three others were associated solely with the risk of prostate cancer, and a fifth was associated with the risk of prostate, colorectal, and ovarian cancer, but not breast cancer. We conclude that there are at least five separate functional variants in this region.