Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer.
Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer.
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DOI：
10.1002/ijc.25554
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发表时间：
2011-05-01
影响因子：
6.4
通讯作者：
Ramus, Susan J.
中科院分区：
文献类型：
--
作者：
Notaridou, Maria;Quaye, Lydia;Dafou, Dimitra;Jones, Chris;Song, Honglin;Hogdall, Estrid;Kjaer, Susanne K.;Christensen, Lise;Hogdall, Claus;Blaakaer, Jan;McGuire, Valerie;Wu, Anna H.;Van den Berg, David J.;Pike, Malcolm C.;Gentry-Maharaj, Aleksandra;Wozniak, Eva;Sher, Tanya;Jacobs, Ian J.;Tyrer, Jonathan;Schildkraut, Joellen M.;Moorman, Patricia G.;Iversen, Edwin S.;Jakubowska, Anna;Medrek, Krzysztof;Lubinski, Jan;Ness, Roberta B.;Moysich, Kirsten B.;Lurie, Galina;Wilkens, Lynne R.;Carney, Michael E.;Wang-Gohrke, Shan;Doherty, Jennifer A.;Rossing, Mary Anne;Beckmann, Matthias W.;Thiel, Falk C.;Ekici, Arif B.;Chen, Xiaoqing;Beesley, Jonathan;Gronwald, Jacek;Fasching, Peter A.;Chang-Claude, Jenny;Goodman, Marc T.;Chenevix-Trench, Georgia;Berchuck, Andrew;Pearce, C. Leigh;Whittemore, Alice S.;Menon, Usha;Pharoah, Paul D. P.;Gayther, Simon A.;Ramus, Susan J.
人群中常见的生殖系遗传变异与上皮性卵巢癌的易感性相关。微细胞介导的染色体转移和表达微阵列分析鉴定了9个与卵巢癌细胞系中致瘤性的功能抑制相关的基因; AIFM 2、AKTIP、AXIN 2、CASP 5、FILIP 1 L、RBBP 8、RGC 32、RUVBL 1和STAG 3。这些基因中的63个标记单核苷酸多态性（tSNP）在1，799例浸润性卵巢癌病例和3，045例对照中进行了基因分型，以寻找与疾病风险的关联。RUVBL 1基因的两个SNPs rs 13063604和rs7650365与浆液性卵巢癌的风险增加相关[HetOR = 1.42（1.15-1.74）和HomOR = 1.63（1.10-1.42），p-trend = 0.0002]和[HetOR = 0.97（0.80-1.17），HomOR = 0.74（0.58-0.93），p-trend = 0.009]。我们对来自美国、欧洲和澳大利亚的另外4,590例病例和6,031例对照进行了rs 13063604和rs7650365基因分型;然而，在第2阶段，两种SNP均不显著。我们还通过检测286例原发性卵巢肿瘤的等位基因特异性杂合性缺失（洛），评估了这9个基因中tSNPs在卵巢癌发生中的潜在作用。我们发现AXIN 2、AKTIP和RGC 32中tSNP的频繁洛（分别为64、46和34%），STAG 3中的一个SNP rs 1637001显示出显著的等位基因特异性洛，94%的信息性肿瘤中常见等位基因丢失（p = 0.015）。阵列比较基因组杂交表明，这种非随机等位基因的不平衡是由于罕见的等位基因的扩增。总之，我们发现了STAG 3的一个常见等位基因参与上皮性卵巢癌发展的证据。
Common germline genetic variation in the population is associated with susceptibility to epithelial ovarian cancer. Microcell-mediated chromosome transfer and expression microarray analysis identified nine genes associated with functional suppression of tumorogenicity in ovarian cancer cell lines; AIFM2, AKTIP, AXIN2, CASP5, FILIP1L, RBBP8, RGC32, RUVBL1 and STAG3. Sixty-three tagging single nucleotide polymorphisms (tSNPs) in these genes were genotyped in 1,799 invasive ovarian cancer cases and 3,045 controls to look for associations with disease risk. Two SNPs in RUVBL1, rs13063604 and rs7650365, were associated with increased risk of serous ovarian cancer [HetOR = 1.42 (1.15–1.74) and the HomOR = 1.63 (1.10–1.42), p-trend = 0.0002] and [HetOR = 0.97 (0.80–1.17), HomOR = 0.74 (0.58–0.93), p-trend = 0.009], respectively. We genotyped rs13063604 and rs7650365 in an additional 4,590 cases and 6,031 controls from ten sites from the United States, Europe and Australia; however, neither SNP was significant in Stage 2. We also evaluated the potential role of tSNPs in these nine genes in ovarian cancer development by testing for allele-specific loss of heterozygosity (LOH) in 286 primary ovarian tumours. We found frequent LOH for tSNPs in AXIN2, AKTIP and RGC32 (64, 46 and 34%, respectively) and one SNP, rs1637001, in STAG3 showed significant allele-specific LOH with loss of the common allele in 94% of informative tumours (p = 0.015). Array comparative genomic hybridisation indicated that this nonrandom allelic imbalance was due to amplification of the rare allele. In conclusion, we show evidence for the involvement of a common allele of STAG3 in the development of epithelial ovarian cancer.
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影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
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Quaye, Lydia;Dafou, Dimitra;Gayther, Simon A.
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