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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：烟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：先前的研究显示，肺癌风险与包含CHRNA5-CHRNA3-CHRNB4烟碱乙酰胆碱受体（nAChR）亚基基因簇的15q25染色体上的单核苷酸多态性（SNP）相关。其他肺nAChRs的遗传变异仍然未知。在这项研究中，我们使用340例非小细胞肺癌病例和435例对照进行了CHRNA9和CHRNA3基因的病例对照分析.CHRNA9基因的外显子2-5的所有外显子，3'UTR，内含子1和其他内含子的一部分以及CHRNA3基因的外显子2、3和周围内含子区域的部分进行了测序。控制该研究的性别，年龄和种族相关差异。通过等位基因频率，基因型分布和单倍型分析评估了分析组中的每个SNP。病例对照分析显示，CHRNA9中的两个SNP rs56159866和rs6819385风险增加，而CHRNA3中的一个SNP rs8040868风险增加。对于CHRNA9，rs55998310，rs56291234和新发现的rs182073550中的三个SNP，以及包含祖先N442α9变体的单倍型NP_060051.2的携带者，这三个SNP的风险均降低了。特性，所有内含子SNP的代名词以及同等作用可能会在转录和/或翻译水平上影响蛋白质的产生，或者只是通过与其他等位基因的遗传连锁而明显地与癌症相关。阐明α9中单个基因变异影响肺癌易感性的机制可能导致开发出个性化的癌症预防和治疗方法，以及防止吸烟的方法。

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