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19p13 常见变异与卵巢癌易感性相关。

Common variants at 19p13 are associated with susceptibility to ovarian cancer.

机构信息

Department of Oncology, University of Cambridge, Cambridge, UK.

出版信息

Nat Genet. 2010 Oct;42(10):880-4. doi: 10.1038/ng.666. Epub 2010 Sep 19.

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5 × 10⁻⁴ and P = 6 × 10⁻⁴, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3 × 10⁻⁹ and P = 4 × 10⁻¹¹, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.

摘要

上皮性卵巢癌(EOC)是发达国家妇科恶性肿瘤死亡的主要原因,占女性癌症死亡人数的 4%。我们对 8951 名上皮性卵巢癌(EOC)患者(病例)的 EOC 生存进行了三阶段全基因组关联研究,这些患者有可用的生存时间数据,并对 EOC 易感性进行了平行关联分析。位于 19p13.11 上的两个 SNP(rs8170 和 rs2363956)显示与生存有关(总 P=5×10⁻⁴和 P=6×10⁻⁴),但在第三阶段没有复制。然而,这两个相同的 SNP 对浆液性 EOC 的风险显示出全基因组意义(P=3×10⁻⁹和 P=4×10⁻¹¹)。在卵巢肿瘤中对该位点候选基因的表达分析支持 BRCA1 相互作用基因 C19orf62(也称为 MERIT40)在 EOC 发展中的作用,该基因包含 rs8170。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01a7/3125495/0c4f5d674661/nihms231460f1.jpg

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