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首页> 外文期刊>Life sciences >New associations of the genetic polymorphisms in nicotinic receptor genes with the risk of lung cancer.
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New associations of the genetic polymorphisms in nicotinic receptor genes with the risk of lung cancer.

机译：脑碱受体基因遗传多态性与肺癌风险的新关联。

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Previous studies revealed association of lung cancer risk with single nucleotide polymorphisms (SNPs) in chromosome 15q25 region containing CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptor (nAChR) subunit gene cluster. The genetic variations in other lung nAChRs remained unknown. In this study, we perform case-control analysis of CHRNA9 and CHRNA3 genes using 340 non-small cell lung cancer cases and 435 controls.All exons, 3'UTR, intron 1 and parts of other introns surrounding exons 2-5 of CHRNA9 gene as well as exons 2, 3 of CHRNA3 gene and parts of surrounding intronic regions were sequenced. The study was controlled for gender, age and ethnicity related differences. Each SNP in analyzed groups was assessed by allele frequency, genotype distribution and haplotype analysis.The case-control analysis revealed that an increased risk is associated with two SNPs in CHRNA9, rs56159866 and rs6819385, and one in CHRNA3, rs8040868. The risk was reduced for three SNPs in CHRNA9, rs55998310, rs56291234, and newly discovered rs182073550, and also in carriers of the haplotype NP_060051.2 containing ancestral N442 variant of α9.The nonsynonymous substitutions can produce receptors exhibiting unique ligand-binding and downstream signaling characteristics, synonymous as well all intronic SNPs may affect protein production at the transcriptional and/or translational levels, or just manifest association with cancer by genetic linkage to other alleles. Elucidation of the mechanisms by which individual genetic variations in α9 affect predisposition to lung cancer may lead to development of personalized approaches to cancer prevention and treatment as well as protection against tobacco consumption.
机译：以前的研究揭示了在染色体15q25区域含有CHRNA5-CHRNA3-CHRNB4烟碱乙酰胆碱受体（nAChR的）亚单位基因簇的单核苷酸多态性（SNP）肺癌的风险相关联。在其他肺部nAChRs的遗传变异不明。在这项研究中，我们执行使用340非小细胞肺癌病例和435个controls.All外显子，3'UTR的CHRNA9和CHRNA3基因病例对照分析，内含子1个零件周围的外显子基因CHRNA9 2-5其他内含子的以及外显子2，CHRNA3基因的3和包围内含子区域的部分进行测序。这项研究是控制了性别，年龄和种族相关的差异。在分析组每个SNP通过等位基因频率，基因型分布评估和单体型浅析浅析病例对照分析表明，增加的风险与在CHRNA9，rs56159866和rs6819385两个SNP，和一个在CHRNA3，rs8040868相关联。风险降低用于CHRNA9，rs55998310，rs56291234 3个SNP，和新发现的rs182073550，并且还含有非同义α9.The取代可以产生受体表现出独特的配体结合和下游信号的祖先N442变体单倍型NP_060051.2的载体特性，同义以及所有内含子的SNP可能影响在转录和/或翻译水平，或通过遗传连锁到其它等位基因与癌症只是清单关联蛋白质生产。由与α9个体遗传变异影响易患肺癌机制的阐明可能导致个性化的方法来预防和治疗癌症以及对烟草消费的保护开发。

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