Genome-wide association study suggests common variants within RP11-634B7.4 gene influencing severe pre-treatment pain in head and neck cancer patients.
Genome-wide association study suggests common variants within RP11-634B7.4 gene influencing severe pre-treatment pain in head and neck cancer patients.
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DOI：
10.1038/srep34206
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发表时间：
2016-09-27
影响因子：
4.6
通讯作者：
Shete S
中科院分区：
文献类型：
--
作者：
Reyes-Gibby CC;Wang J;Silvas MR;Yu RK;Hanna EY;Shete S
疼痛通常是头颈部鳞状细胞癌（HNSCC）的最初体征之一。诊断时的疼痛是慢性疼痛发展的重要预后指标，重要的是，对于总生存时间。为了确定影响1，368例新诊断为HNSCC患者治疗前严重疼痛的变异，我们基于730，525个标签SNP进行了全基因组关联研究。这些患者以前都没有接受过癌症治疗。约15%的患者有重度治疗前疼痛，定义为疼痛评分≥7（0 =“无疼痛”，10 =“最严重疼痛”）。我们发现了3种常见的高度连锁不平衡的遗传变异，代表了1 q44的一个基因组区域（rs3862188，P = 3.45 × 10−8; rs880143，P = 3.45 × 10−8;和rs7526880，P = 4.92 × 10−8），其定位于RP 11 - 634 B7.4基因，一种新的三种嗅觉受体基因的反义基因。嗅觉受体基因是MAPK信号级联反应的上游效应子，可能是HNSCC患者疼痛的新靶基因。未来探索生物学机制的实验验证将是确定内含子变体和非编码RNA在HNSCC患者疼痛中的作用的关键。
Pain is often one of the first signs of squamous cell carcinoma of the head and neck (HNSCC). Pain at diagnosis is an important prognostic marker for the development of chronic pain, and importantly, for the overall survival time. To identify variants influencing severe pre-treatment pain in 1,368 patients newly diagnosed with HNSCC, we conducted a genome-wide association study based on 730,525 tagging SNPs. The patients were all previously untreated for cancer. About 15% of the patients had severe pre-treatment pain, defined as pain score ≥7 (0 = “no pain” and 10 = “worst pain”). We identified 3 common genetic variants in high linkage disequilibrium for severe pre-treatment pain, representing one genomic region at 1q44 (rs3862188, P = 3.45 × 10−8; rs880143, P = 3.45 × 10−8; and rs7526880, P = 4.92 × 10−8), which maps to the RP11-634B7.4 gene, a novel antisense gene to three olfactory receptor genes. Olfactory receptor genes, upstream effectors of the MAPK signaling cascade, might be novel target genes for pain in HNSCC patients. Future experimental validation to explore biological mechanisms will be key to defining the role of the intronic variants and non-coding RNA for pain in patients with HNSCC.
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DOI：
10.1016/s0197-2456(98)00037-3
发表时间：
1998-12-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
Dupont, WD;Plummer, WD
通讯作者：
Plummer, WD
影响因子：
1.9
作者：
Lee, WC
通讯作者：
Lee, WC
影响因子：
3.8
作者：
Kang N;Koo J
通讯作者：
Koo J
影响因子：
64.8
作者：
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通讯作者：
Smith AJ
影响因子：
9.3
作者：
St Laurent G;Vyatkin Y;Kapranov P
通讯作者：
Kapranov P