Potential Susceptibility Loci Identified for Renal Cell Carcinoma by Targeting Obesity-Related Genes.
Potential Susceptibility Loci Identified for Renal Cell Carcinoma by Targeting Obesity-Related Genes.
复制标题
通过针对肥胖相关基因鉴定出肾细胞癌的潜在易感基因座。
DOI：
10.1158/1055-9965.epi-17-0141
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Wu,Xifeng
中科院分区：
文献类型：
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作者：
Shu,Xiang;Purdue,MarkP;Ye,Yuanqing;Tu,Huakang;Wood,ChristopherG;Tannir,NizarM;Wang,Zhaoming;Albanes,Demetrius;Gapstur,SusanM;Stevens,VictoriaL;Rothman,Nathaniel;Chanock,StephenJ;Wu,Xifeng
背景：肥胖是肾细胞癌（RCC）的危险因素。尽管RCC的全基因组关联研究（GWAS）已经确定了几个易感位点，但由于高度保守的选择，可能会遗漏其他变异。方法：我们在MD安德森癌症中心（MDA RCC GWAS和MDA RCC OncoArray）和国家癌症研究所（NCI RCC GWAS）进行了一项多阶段研究，利用三个独立的全基因组扫描，共包括3,530例病例和5,714例对照，研究肥胖相关基因的遗传变异和RCC风险。结果：在发现阶段，从MDA RCC GWAS中提取了2001个肥胖相关基因的32,946个snp，位于±10 kb，并使用多变量logistic回归进行分析。如果验证集中的snp没有直接基因分型，则搜索代理（R2 bb0 0.8）或进行代入。随后在MDA RCC OncoArray中评估MDA RCC GWAS和NCI RCC GWAS中p < 0.05的21个snp。在整体荟萃分析中，观察到与RCC风险显著（P< 0.05）相关的SNP映射：toIL1RAPL2[rs10521506-G: ORmeta= 0.87 (0.81-0.93),Pmeta= 2.33 × 10−5],PLIN2[rs2229536-A: ORmeta= 0.87 (0.81-0.93),Pmeta= 2.33 × 10−5],SMAD3[rs4601989-A: ORmeta= 0.86 (0.80-0.93),Pmeta= 2.71 × 10−4],MED13L[rs10850596-A: ORmeta= 1.14 (1.07-1.23),Pmeta= 1.50 × 10−4],tsc1 [rs3761840-G: ORmeta= 0.90 (0.85-0.97),Pmeta= 2.47 × 10−3]。在TCGA KIRC数据中，我们没有观察到这些snp有任何显著的顺式表达数量性状位点效应。结论：综上所述，我们发现肥胖相关基因的遗传变异可能影响RCC的易感性。影响：这五个已确定的基因座可能为揭示肥胖相关基因在RCC发展中的重要性提供新的疾病病因学见解。癌症流行病学生物标志物；26日(9);1436 - 42。AACR©2017。
Background:Obesity is an established risk factor for renal cell carcinoma (RCC). Although genome-wide association studies (GWAS) of RCC have identified several susceptibility loci, additional variants might be missed due to the highly conservative selection.Methods:We conducted a multiphase study utilizing three independent genome-wide scans at MD Anderson Cancer Center (MDA RCC GWAS and MDA RCC OncoArray) and National Cancer Institute (NCI RCC GWAS), which consisted of a total of 3,530 cases and 5,714 controls, to investigate genetic variations in obesity-related genes and RCC risk.Results:In the discovery phase, 32,946 SNPs located at ±10 kb of 2,001 obesity-related genes were extracted from MDA RCC GWAS and analyzed using multivariable logistic regression. Proxies (R2> 0.8) were searched or imputation was performed if SNPs were not directly genotyped in the validation sets. Twenty-one SNPs withP< 0.05 in both MDA RCC GWAS and NCI RCC GWAS were subsequently evaluated in MDA RCC OncoArray. In the overall meta-analysis, significant (P< 0.05) associations with RCC risk were observed for SNP mapping toIL1RAPL2[rs10521506-G: ORmeta= 0.87 (0.81–0.93),Pmeta= 2.33 × 10−5],PLIN2[rs2229536-A: ORmeta= 0.87 (0.81–0.93),Pmeta= 2.33 × 10−5],SMAD3[rs4601989-A: ORmeta= 0.86 (0.80–0.93),Pmeta= 2.71 × 10−4],MED13L[rs10850596-A: ORmeta= 1.14 (1.07–1.23),Pmeta= 1.50 × 10−4], andTSC1[rs3761840-G: ORmeta= 0.90 (0.85–0.97),Pmeta= 2.47 × 10−3]. We did not observe any significant cis-expression quantitative trait loci effect for these SNPs in the TCGA KIRC data.Conclusions:Taken together, we found that genetic variation of obesity-related genes could influence RCC susceptibility.Impact:The five identified loci may provide new insights into disease etiology that reveal importance of obesity-related genes in RCC development.Cancer Epidemiol Biomarkers Prev; 26(9); 1436–42. ©2017 AACR.