HSD3B and gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer.
HSD3B and gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer.
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DOI：
10.1371/journal.pone.0051301
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Karagas MR
中科院分区：
文献类型：
--
作者：
Andrew AS;Hu T;Gu J;Gui J;Ye Y;Marsit CJ;Kelsey KT;Schned AR;Tanyos SA;Pendleton EM;Mason RA;Morlock EV;Zens MS;Li Z;Moore JH;Wu X;Karagas MR
膀胱癌是美国男性中第四常见的癌症。我们分析了变异基因型，这些变异基因型被假设为改变参与膀胱癌发生的主要生物学过程，包括激素调节、细胞凋亡、DNA修复、免疫监视、代谢、增殖和端粒维持。在美国新罕布什尔州进行的一项膀胱癌病例对照研究中，我们采用Logistic回归分析评估了影响这些过程的遗传变异与563例基因型尿路上皮细胞癌病例和863例对照的易感性之间的关系。我们采用多因素重复性降低（MDR）和统计上位性网络分析评估了基因-基因相互作用。在新罕布什尔州人群中，激素调节基因HSD 3B 2的3′UTR侧翼变异形式与膀胱癌风险增加相关（校正OR 1.85 95%CI 1.31-2.62）。在德克萨斯州膀胱癌研究中，957例对照，497例病例（校正OR 3.66 95%CI 1.06-12.63）成功复制了这一发现。男性（OR 2.13 95%CI 1.40-3.25）比女性（OR 1.56 95%CI 0.83-2.95）更强（SNP-性别交互作用P = 0.048）。 我们还鉴定了T细胞活化相关基因GATA 3和CD 81之间的SNP-SNP相互作用（相互作用P = 0.0003）。 男性膀胱癌发病率高3-4倍的事实表明与激素水平有关。这种基于生物学过程的分析提出了候选的易感性标志物，并支持了激素调节紊乱在膀胱癌发生中起作用的理论。
Bladder cancer is the 4th most common cancer among men in the U.S. We analyzed variant genotypes hypothesized to modify major biological processes involved in bladder carcinogenesis, including hormone regulation, apoptosis, DNA repair, immune surveillance, metabolism, proliferation, and telomere maintenance. Logistic regression was used to assess the relationship between genetic variation affecting these processes and susceptibility in 563 genotyped urothelial cell carcinoma cases and 863 controls enrolled in a case–control study of incident bladder cancer conducted in New Hampshire, U.S. We evaluated gene–gene interactions using Multifactor Dimensionality Reduction (MDR) and Statistical Epistasis Network analysis. The 3′UTR flanking variant form of the hormone regulation gene HSD3B2 was associated with increased bladder cancer risk in the New Hampshire population (adjusted OR 1.85 95%CI 1.31–2.62). This finding was successfully replicated in the Texas Bladder Cancer Study with 957 controls, 497 cases (adjusted OR 3.66 95%CI 1.06–12.63). The effect of this prevalent SNP was stronger among males (OR 2.13 95%CI 1.40–3.25) than females (OR 1.56 95%CI 0.83–2.95), (SNP-gender interaction P = 0.048). We also identified a SNP-SNP interaction between T-cell activation related genes GATA3 and CD81 (interaction P = 0.0003). The fact that bladder cancer incidence is 3–4 times higher in males suggests the involvement of hormone levels. This biologic process-based analysis suggests candidate susceptibility markers and supports the theory that disrupted hormone regulation plays a role in bladder carcinogenesis.
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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
使用统计上居性网络在人类疾病关联研究中表征遗传相互作用。
影响因子：
3
作者：
Hu T;Sinnott-Armstrong NA;Kiralis JW;Andrew AS;Karagas MR;Moore JH
通讯作者：
Moore JH
影响因子：
--
作者：
Bartsch, H;Rojas, M;Alexandrov, K
通讯作者：
Alexandrov, K
影响因子：
5.3
作者：
Andrew AS;Gui J;Sanderson AC;Mason RA;Morlock EV;Schned AR;Kelsey KT;Marsit CJ;Moore JH;Karagas MR
通讯作者：
Karagas MR
影响因子：
8.4
作者：
Dietrich, K.;Demidenko, E.;Schned, A.;Zens, M. S.;Heaney, J.;Karagas, M. R.
通讯作者：
Karagas, M. R.