Variations in chromosomes 9 and 6p21.3 with risk of non-Hodgkin lymphoma.
Variations in chromosomes 9 and 6p21.3 with risk of non-Hodgkin lymphoma.
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染色体9和6P21.3的变化，有非霍奇金淋巴瘤的风险。
DOI：
10.1158/1055-9965.epi-10-0638
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发表时间：
2011-01
期刊：
影响因子：
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通讯作者：
Morton LM
中科院分区：
文献类型：
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作者：
Wang SS;Menashe I;Cerhan JR;Cozen W;Severson RK;Davis S;Hutchinson A;Rothman N;Chanock SJ;Bernstein L;Hartge P;Morton LM
越来越多的证据表明遗传变异与非霍奇金淋巴瘤（NHL）病因有关。为了补充正在进行的不可知的方法来确定易感基因，我们评估了488个候选基因区域及其与NHL和NHL亚型风险的关系。我们对来自美国多中心病例对照研究的947例病例和826例基于人群的对照进行了6，679个标签单核苷酸多态性（SNP）基因分型。通过在10，000个排列的基础上计算最小P值（“minP检验”）来获得关联的基因水平总结。我们使用逻辑回归来评估基因型和单倍型与NHL之间的关联。对于NHL亚型，我们进行了多分类多变量非条件Logistic回归（调整性别，种族，年龄）。我们在共显性模型下计算每个SNP的P趋势。14个基因区域与NHL相关（P < 0.01）。与NHL相关的最显著的SNP映射到SYK基因（rs 2991216，P趋势= 0.00005）。三个最显著的基因区域位于染色体6p21.3（RING 1/RXRB; AIF 1; BAT 4）。因此，RING 1/RXRB（rs 2855429）、AIF 1（rs 2857597）和BAT 4（rs3115667）中的SNP与NHL（P趋势≤ 0.0002）以及弥漫性大B细胞淋巴瘤和滤泡性淋巴瘤（P趋势< 0.05）相关。我们的研究结果表明，9号染色体上的SYK与NHL病因的潜在重要性。我们的研究结果进一步牵连6p21.3基因变异，支持需要充分表征这一染色体区域的淋巴瘤发生。9号染色体上的基因变异可能代表了NHL病因学的一个新的有趣区域。报道的6p21.3变异与相关变异（TNF/HLA）的独立性支持了确认该区域致病变异的需要
There is growing evidence linking genetic variations to non–Hodgkin lymphoma (NHL) etiology. To complement ongoing agnostic approaches for identifying susceptibility genes, we evaluated 488 candidate gene regions and their relation to risk for NHL and NHL subtypes. We genotyped 6,679 tag single nucleotide polymorphisms (SNPs) in 947 cases and 826 population-based controls from a multicenter U.S. case–control study. Gene-level summary of associations were obtained by computing the minimum P value (“minP test”) on the basis of 10,000 permutations. We used logistic regression to evaluate the association between genotypes and haplotypes with NHL. For NHL subtypes, we conducted polytomous multivariate unconditional logistic regression (adjusted for sex, race, age). We calculated P-trends under the codominant model for each SNP. Fourteen gene regions were associated with NHL (P < 0.01). The most significant SNP associated with NHL maps to the SYK gene (rs2991216, P-trend = 0.00005). The three most significant gene regions were on chromosome 6p21.3 (RING1/RXRB; AIF1; BAT4). Accordingly, SNPs in RING1/RXRB (rs2855429), AIF1 (rs2857597), and BAT4 (rs3115667) were associated with NHL (P-trends ≤ 0.0002) and both diffuse large B-cell and follicular lymphomas (P-trends < 0.05). Our results suggest potential importance for SYK on chromosome 9 with NHL etiology. Our results further implicate 6p21.3 gene variants, supporting the need for full characterization of this chromosomal region in relation to lymphomagenesis. Gene variants on chromosome 9 may represent a new region of interesting for NHL etiology. The independence of the reported variants in 6p21.3 from implicated variants (TNF/HLA) supports the need to confirm causal variants in this region