Sequence variant on 8q24 confers susceptibility to urinary bladder cancer.
Sequence variant on 8q24 confers susceptibility to urinary bladder cancer.
复制标题
DOI：
10.1038/ng.229
复制
发表时间：
2008-11
期刊：
影响因子：
30.8
通讯作者：
Stefansson K
中科院分区：
文献类型：
--
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
我们对来自冰岛和荷兰的 1,803 例膀胱癌 (UBC) 病例和 34,336 例对照进行了全基因组 SNP 关联研究，并对另外 7 个病例对照组（2,165 例病例和 3,800 例对照）进行了后续研究。最强的关联性与位于 c-Myc 基因上游 30kb 的染色体 8q24 上 rs9642880 的等位基因 T 观察到（等位基因特异性 OR=1.22；P=9.34×10−12）。大约 20% 的欧洲血统个体是 rs9642880 (T) 纯合子，他们患 UBC 的估计风险是非携带者的 1.49 倍，群体归因风险 (PAR) 为 17%。在 UBC 和之前与前列腺癌、结直肠癌和乳腺癌相关的四种 8q24 变异之间没有观察到关联，rs9642880 也与这三种癌症中的任何一种都没有关联。位于染色体 3q28 上 TP63 基因附近的 rs710521 (A) 捕获了较弱的信号，但仍然具有全基因组意义（等位基因特异性 OR=1.19；P=1. 15× 10−7）。
We conducted a genome wide SNP association study on 1,803 Urinary Bladder Cancer (UBC) cases and 34,336 controls from Iceland and the Netherlands and follow up studies in seven additional case control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30kb upstream of the c-Myc gene (allele specific OR=1.22; P=9.34×10−12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880 (T) and their estimated risk of developing UBC is 1.49 times that of non-carriers with population attributable risk (PAR) of 17%. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome wide significance, was captured by rs710521 (A) located near the TP63 gene on chromosome 3q28 (allele specific OR=1.19; P=1. 15× 10−7).