A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
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作者：
以前，我们报道了荷兰和冰岛受试者中与膀胱癌（UBC）风险相关的生殖系DNA变异。在这里，我们扩展了冰岛的样本集，并在几个欧洲病例对照样本集中测试了来自联合分析的前20个标志物，共有4，739例病例和45，549例对照。发现4p16.3上rs798766的T等位基因与UBC相关（优势比= 1.24，P = 9.9 × 10−12）。rs798766位于TACC3的内含子中，距离FGFR3 70 kb，其通常在低级别，非侵入性UBC中携带激活体细胞突变。值得注意的是，rs798766[T]与低级别和低阶段UBC的相关性比与更具侵袭性的疾病形式的相关性更强，并且与低级别阶段Ta肿瘤的复发风险更高相关。rs798766[T]在携带FGFR 3激活突变的Ta肿瘤中的频率高于具有野生型FGFR 3的Ta肿瘤。我们的研究结果显示了FGFR3的种系变异、体细胞突变和UBC风险之间的联系。
Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 × 10−12). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
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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：
11.2
作者：
Tomlinson, DC;L'Hôte, CG;Knowles, MA
通讯作者：
Knowles, MA
影响因子：
--
作者：
Parkin, D. Maxwell
通讯作者：
Parkin, D. Maxwell
影响因子：
4.7
作者：
Wallerand, H;Bakkar, AA;Chopin, DK
通讯作者：
Chopin, DK
影响因子：
30.8
作者：
Kong A;Masson G;Frigge ML;Gylfason A;Zusmanovich P;Thorleifsson G;Olason PI;Ingason A;Steinberg S;Rafnar T;Sulem P;Mouy M;Jonsson F;Thorsteinsdottir U;Gudbjartsson DF;Stefansson H;Stefansson K
通讯作者：
Stefansson K