New associations of the genetic polymorphisms in nicotinic receptor genes with the risk of lung cancer.
New associations of the genetic polymorphisms in nicotinic receptor genes with the risk of lung cancer.
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DOI：
10.1016/j.lfs.2011.12.023
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发表时间：
2012-11-27
期刊：
影响因子：
6.1
通讯作者：
Grando, Sergei A.
中科院分区：
文献类型：
--
作者：
Chikova, Anna;Bernard, Hans-Ulrich;Shchepotin, Igor B.;Grando, Sergei A.
关键词：
既往研究发现，肺癌风险与含有CHRNA5-CHRNA3-CHRNB4烟碱乙酰胆碱受体（nAChR）亚基基因簇的染色体15q25区域的单核苷酸多态性（snp）相关。其他肺nachr的遗传变异尚不清楚。在这项研究中，我们对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。对CHRNA9基因2 - 5外显子周围的所有外显子、3 ' utr、内含子1和部分内含子以及CHRNA3基因2、3外显子和周围部分内含子区进行测序。该研究对性别、年龄和种族相关差异进行了控制。通过等位基因频率、基因型分布和单倍型分析对各分析组的SNP进行评估。病例对照分析显示，风险增加与CHRNA9中的两个snp （rss56159866和rs6819385）以及CHRNA3中的一个snp （rs8040868）有关。在CHRNA9、rs55998310、rss56291234和新发现的ss410759555，以及含有祖先α9变异N442的单倍型NP_060051.2携带者中，风险降低。非同义替换可以产生具有独特配体结合和下游信号特征的受体，同义替换以及所有内含子snp都可能在转录和/或翻译水平上影响蛋白质的产生，或者仅仅通过与其他等位基因的遗传连锁与癌症表现出关联。阐明个体α9基因变异影响肺癌易感性的机制可能有助于开发个性化的癌症预防和治疗方法，以及防止烟草消费。
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 ss410759555, 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.
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DOI：
10.1073/pnas.87.9.3294
发表时间：
1990-05-01
影响因子：
11.1
作者：
MANECKJEE, R;MINNA, JD
通讯作者：
MINNA, JD
影响因子：
15.9
作者：
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通讯作者：
Dennis, PA
影响因子：
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作者：
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通讯作者：
Criado, M
影响因子：
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作者：
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通讯作者：
Paschoal, Marcos Eduardo Machado
影响因子：
5.3
作者：
Novak, J;Escobedo-Morse, A;Kane, MA
通讯作者：
Kane, MA