Genetic variation in tumor necrosis factor and lymphotoxin-alpha (TNF-LTA) and breast cancer risk
Genetic variation in tumor necrosis factor and lymphotoxin-alpha (TNF-LTA) and breast cancer risk
复制标题
DOI：
10.1007/s00439-006-0315-x
复制
发表时间：
2007-05-01
期刊：
影响因子：
5.3
通讯作者：
Garcia-Closas, Montserrat
中科院分区：
文献类型：
--
作者：
Gaudet, Mia M.;Egan, Kathleen M.;Garcia-Closas, Montserrat
肿瘤坏死因子（TNF）是调节炎症的关键。TNF启动子区的遗传变异与表达差异以及一系列自身免疫、感染和肿瘤疾病相关。我们分析了8种常见的单核苷酸多态性（SNP）（rs746868、rs 909253、rs 1799964、rs 1800630、rs 1800750、rs 1800629、rs361525和rs 1800610）以捕获TNF中的大部分遗传变异以及α-光毒素（LTA）中的SNP，一种与TNF启动子区连锁不平衡的促炎细胞因子。在美国基于人群的病例对照研究中对SNP进行基因分型（3，318例病例，2，841例对照）。在波兰进行的一项独立的基于人群的病例对照研究（2，228例，2，378例对照）中随访了有希望的结果。在这两项研究中，携带rs361525变异等位基因的女性患乳腺癌的风险高于GG基因型（每个等位基因OR = 1.18，95% CI 1.04-1.35;趋势P = 0.008）。其他SNPs与乳腺癌风险无显著相关性。单倍型分析没有发现TNF和乳腺癌风险之间有任何额外的关联。来自5，269例病例和4，982例对照的数据表明，位于TNF启动子区域的rs361525 A等位基因与乳腺癌风险的适度增加相关。需要进一步的研究来复制这些发现，并确定rs361525是一个致病的SNP还是一个致病SNP的标记。
Tumor necrosis factor (TNF) is critical to regulation of inflammation. Genetic variation in the promoter region of TNF has been associated with expression differences, and a range of auto-immune, infectious, and oncologic diseases. We analyzed eight common single nucleotide polymorphisms (SNPs) (rs746868, rs909253, rs1799964, rs1800630, rs1800750, rs1800629, rs361525, and rs1800610) to capture most of the genetic variation in TNF in addition to SNPs in lymphotoxin-alpha (LTA), a pro-inflammatory cytokine in linkage disequilibrium with the TNF promoter region. SNPs were genotyped in a USA population-based case-control study (3,318 cases, 2,841 controls). Promising results were followed-up in an independent population-based case-control study in Poland (2,228 cases, 2,378 controls). In both studies, women carrying the variant allele of rs361525 were at elevated breast cancer risk compared to the GG genotype (per allele OR = 1.18, 95% CI 1.04-1.35; P for trend = 0.008). Other SNPs were not significantly associated with breast cancer risk. Haplotype analyses did not reveal any additional associations between TNF and breast cancer risk. Data from 5,269 cases and 4,982 controls suggested that the rs361525 A allele, located in the TNF promoter region, was associated with a modest increase in breast cancer risk. Additional studies are required to replicate these findings and to determine whether rs361525 is a causative SNP or is a marker of a causative SNP.