A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24.
A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24.
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卵巢癌（OC）的死亡人数超过所有其他妇科癌症的总和。为了识别常见的低突变率OC易感基因，我们对1,768例病例和2,354例对照中的507,094个SNP进行了全基因组关联研究（GWAS），并对4,162例病例和4,810例对照中的21,955个SNP进行了随访，从而确定了9 p22（BNC 2）的确认易感基因座。在此，我们报告了9个额外的候选基因座（p≤10-4），这些基因座是在对病例进行组织学分层后确定的，并在另外4,353例病例和6,021例对照中进行了基因分型。两个新的易感位点p≤5×10-8得到确认（8 q24，p=8.0×10-15和2 q31，p=3.8×10-14）;另外两个位点也被确定为接近全基因组意义（3q 25，p=7.1×10-8和17 q21，p=1.4×10-7）。与浆液性OC的相关性通常强于其他亚型。HOXD 1，MYC，TiPARP和SKAP 1在这些位点的分析，和BNC 2在9 p22，支持这些基因在OC的发展中的功能作用。
Ovarian cancer (OC) accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance OC susceptibility genes, we conducted a genome-wide association study (GWAS) of 507,094 SNPs in 1,768 cases and 2,354 controls, with follow-up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (BNC2). Here, we report on nine additional candidate loci (p≤10-4), identified after stratifying cases by histology, genotyped in an additional 4,353 cases and 6,021 controls. Two novel susceptibility loci with p≤5×10-8 were confirmed (8q24, p=8.0×10-15 and 2q31, p=3.8×10-14); two additional loci were also identified that approached genome-wide significance (3q25, p=7.1×10-8 and 17q21, p=1.4×10-7). The associations with serous OC were generally stronger than other subtypes. Analysis of HOXD1, MYC, TiPARP, and SKAP1 at these loci, and BNC2 at 9p22, supports a functional role for these genes in OC development.
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影响因子：
30.8
作者：
Kiemeney LA;Thorlacius S;Sulem P;Geller F;Aben KK;Stacey SN;Gudmundsson J;Jakobsdottir M;Bergthorsson JT;Sigurdsson A;Blondal T;Witjes JA;Vermeulen SH;Hulsbergen-van de Kaa CA;Swinkels DW;Ploeg M;Cornel EB;Vergunst H;Thorgeirsson TE;Gudbjartsson D;Gudjonsson SA;Thorleifsson G;Kristinsson KT;Mouy M;Snorradottir S;Placidi D;Campagna M;Arici C;Koppova K;Gurzau E;Rudnai P;Kellen E;Polidoro S;Guarrera S;Sacerdote C;Sanchez M;Saez B;Valdivia G;Ryk C;de Verdier P;Lindblom A;Golka K;Bishop DT;Knowles MA;Nikulasson S;Petursdottir V;Jonsson E;Geirsson G;Kristjansson B;Mayordomo JI;Steineck G;Porru S;Buntinx F;Zeegers MP;Fletcher T;Kumar R;Matullo G;Vineis P;Kiltie AE;Gulcher JR;Thorsteinsdottir U;Kong A;Rafnar T;Stefansson K
通讯作者：
Stefansson K
影响因子：
8
作者：
Shiraishi, M;Sekiguchi, A;Miyamoto, Y
通讯作者：
Miyamoto, Y
影响因子：
30.8
作者：
Tomlinson, Ian P. M.;Webb, Emily;Houlston, Richard S.
通讯作者：
Houlston, Richard S.
影响因子：
11.5
作者：
Lakhani, SR;Manek, S;Easton, DF
通讯作者：
Easton, DF
影响因子：
8.5
作者：
Lawrenson, K.;Benjamin, E.;Dafou, D.
通讯作者：
Dafou, D.