Genetic variation in DNA repair pathways and risk of non-Hodgkin's lymphoma.
Genetic variation in DNA repair pathways and risk of non-Hodgkin's lymphoma.
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DOI：
10.1371/journal.pone.0101685
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kirchhoff T
中科院分区：
文献类型：
--
作者：
Rendleman J;Antipin Y;Reva B;Adaniel C;Przybylo JA;Dutra-Clarke A;Hansen N;Heguy A;Huberman K;Borsu L;Paltiel O;Ben-Yehuda D;Brown JR;Freedman AS;Sander C;Zelenetz A;Klein RJ;Shao Y;Lacher M;Vijai J;Offit K;Kirchhoff T
分子和遗传证据表明，DNA修复途径可能有助于淋巴瘤易感性。一些研究已经检查了DNA修复基因与淋巴瘤风险的关系，但这些报告的结果并不一致。在这里，我们提供了DNA修复基因遗传变异的集中分析结果及其与非霍奇金淋巴瘤（NHL）风险的关系。在1,297例NHL病例和1,946例对照人群中，我们对标记81个DNA修复基因遗传变异的446个单核苷酸多态性（snp）进行了两阶段的病例/对照关联分析。我们发现ATM位点rs227060与NHL风险的相关性最显著（OR = 1.27, 95% CI: 1.13-1.43, p = 6.77×10−5），经多重检验调整后，这一相关性仍然显著。在一项亚型特异性分析中，也观察到弥漫性大b细胞淋巴瘤（DLBCL）和小淋巴细胞淋巴瘤（SLL）中ATM位点的相关性，但在滤泡性淋巴瘤（FL）中没有观察到相关性。此外，我们的研究提供了MRE11A和NBS1 snp之间相互作用与NHL风险相关的提示证据（OR = 0.51, 95% CI: 0.34-0.77, p = 0.0002）。最后，利用1000个基因组计划数据结合功能预测分析进行的归算分析显示，存在与观察到的关联信号相关的生物学相关变异。虽然本文的研究结果需要独立验证，但我们的大型研究结果表明，ATM可能是一个与多种NHL亚型风险相关的新位点。
Molecular and genetic evidence suggests that DNA repair pathways may contribute to lymphoma susceptibility. Several studies have examined the association of DNA repair genes with lymphoma risk, but the findings from these reports have been inconsistent. Here we provide the results of a focused analysis of genetic variation in DNA repair genes and their association with the risk of non-Hodgkin's lymphoma (NHL). With a population of 1,297 NHL cases and 1,946 controls, we have performed a two-stage case/control association analysis of 446 single nucleotide polymorphisms (SNPs) tagging the genetic variation in 81 DNA repair genes. We found the most significant association with NHL risk in the ATM locus for rs227060 (OR = 1.27, 95% CI: 1.13–1.43, p = 6.77×10−5), which remained significant after adjustment for multiple testing. In a subtype-specific analysis, associations were also observed for the ATM locus among both diffuse large B-cell lymphomas (DLBCL) and small lymphocytic lymphomas (SLL), however there was no association observed among follicular lymphomas (FL). In addition, our study provides suggestive evidence of an interaction between SNPs in MRE11A and NBS1 associated with NHL risk (OR = 0.51, 95% CI: 0.34–0.77, p = 0.0002). Finally, an imputation analysis using the 1,000 Genomes Project data combined with a functional prediction analysis revealed the presence of biologically relevant variants that correlate with the observed association signals. While the findings generated here warrant independent validation, the results of our large study suggest that ATM may be a novel locus associated with the risk of multiple subtypes of NHL.
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影响因子：
64.5
作者：
Alt FW;Zhang Y;Meng FL;Guo C;Schwer B
通讯作者：
Schwer B
影响因子：
--
作者：
Bednarski JJ;Sleckman BP
通讯作者：
Sleckman BP
影响因子：
64.5
作者：
Baca SC;Prandi D;Lawrence MS;Mosquera JM;Romanel A;Drier Y;Park K;Kitabayashi N;MacDonald TY;Ghandi M;Van Allen E;Kryukov GV;Sboner A;Theurillat JP;Soong TD;Nickerson E;Auclair D;Tewari A;Beltran H;Onofrio RC;Boysen G;Guiducci C;Barbieri CE;Cibulskis K;Sivachenko A;Carter SL;Saksena G;Voet D;Ramos AH;Winckler W;Cipicchio M;Ardlie K;Kantoff PW;Berger MF;Gabriel SB;Golub TR;Meyerson M;Lander ES;Elemento O;Getz G;Demichelis F;Rubin MA;Garraway LA
通讯作者：
Garraway LA
影响因子：
20.3
作者：
Camacho, E;Hernández, L;Campo, E
通讯作者：
Campo, E
影响因子：
1.7
作者：
Baris, Safa;Celkan, Tiraje;Yildiz, Inci
通讯作者：
Yildiz, Inci