Common genetic variants in the 9p21 region and their associations with multiple tumours.
Common genetic variants in the 9p21 region and their associations with multiple tumours.
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DOI：
10.1038/bjc.2013.7
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发表时间：
2013-04-02
影响因子：
8.8
通讯作者：
Yang, X. R.
中科院分区：
文献类型：
--
作者：
Gu, F.;Pfeiffer, R. M.;Bhattacharjee, S.;Han, S. S.;Taylor, P. R.;Berndt, S.;Yang, H.;Sigurdson, A. J.;Toro, J.;Mirabello, L.;Greene, M. H.;Freedman, N. D.;Abnet, C. C.;Dawsey, S. M.;Hu, N.;Qiao, Y-L;Ding, T.;Brenner, A. V.;Garcia-Closas, M.;Hayes, R.;Brinton, L. A.;Lissowska, J.;Wentzensen, N.;Kratz, C.;Moore, L. E.;Ziegler, R. G.;Chow, W-H;Savage, S. A.;Burdette, L.;Yeager, M.;Chanock, S. J.;Chatterjee, N.;Tucker, M. A.;Goldstein, A. M.;Yang, X. R.
染色体9p21.3区域与多种癌症的发病机制有关。本研究系统地检测了甲状腺癌、子宫内膜癌（EC）、肾细胞癌、结直肠癌（CRC）、结直肠腺瘤（CA）、食管鳞状细胞癌（ESCC）、贲门腺癌和骨肉瘤（OS）8个病例对照研究中9p21.3（19.9-32.8 Mb）上22个基因的203个标记SNP。我们使用逻辑回归分别对每项研究进行单SNP分析，并对研究特定的协变量进行调整。我们通过固定效应荟萃分析和新开发的基于子集的统计方法（ASSET）将研究中的SNP结果结合起来。使用自适应秩截尾乘积程序通过minP方法获得基于基因的P值。我们通过Bonferroni校正调整了多重比较。细胞周期蛋白依赖性激酶抑制剂2A（CDKN 2A）中的Rs3731239与ESCC显著相关（P=7 × 10−6）。基于基因的分析进一步支持了CDKN 2A-ESCC相关性（Pgene=0.0001）。在ASSET的荟萃分析中，4个SNP（CDKN 2A中的rs3731239，CDKN 2B中的rs615552和rs 573687以及CDKN 2BAS中的rs 564398）与ESCC和EC显著相关（P<2.46 × 10−4）。MTAP（甲硫腺苷磷酸化酶）中的一个SNP（rs7023329）先前在多个全基因组关联研究中与黑色素瘤和痣相关，但通过ASSET与CRC、CA和OS相关（P=0.007）。我们的数据表明，CDKN 2A的遗传变异以及可能的附近基因可能与ESCC和其他几种肿瘤相关，进一步突出了9p21.3遗传变异在致癌作用中的重要性。
The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9–32.8 Mb) in eight case–control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10−6). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P<2.46 × 10−4). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P=0.007). Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.
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影响因子：
4.7
作者：
Driver KE;Song H;Lesueur F;Ahmed S;Barbosa-Morais NL;Tyrer JP;Ponder BA;Easton DF;Pharoah PD;Dunning AM;Studies in Epidemiology and Risks of Cancer Heredity (SEARCH) Team
通讯作者：
Studies in Epidemiology and Risks of Cancer Heredity (SEARCH) Team
影响因子：
3.8
作者：
Gao Y;Hu N;Han X;Giffen C;Ding T;Goldstein A;Taylor P
通讯作者：
Taylor P
DOI：
10.1158/1055-9965.epi-08-0704
发表时间：
2009-01
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Mavaddat N;Dunning AM;Ponder BA;Easton DF;Pharoah PD
通讯作者：
Pharoah PD
影响因子：
3.8
作者：
Gu, Jian;Horikawa, Yohei;Wu, Xifeng
通讯作者：
Wu, Xifeng
影响因子：
2.6
作者：
Neta, Gila;Yu, Chu-Ling;Brenner, Alina;Gu, Fangyi;Hutchinson, Amy;Pfeiffer, Ruth;Sturgis, Erich M.;Xu, Li;Linet, Martha S.;Alexander, Bruce H.;Chanock, Stephen;Sigurdson, Alice J.
通讯作者：
Sigurdson, Alice J.