CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

Shen, Bo; Zhu, Qun; Zheng, Ming‐Hua; Chen, Jia; Shi, Meiqi; Feng, Jifeng

doi:10.1590/1414-431x20122451

Cited by 7 publications

(7 citation statements)

References 19 publications

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“…CHRNA5 is located in 15q25.1 and belongs to the superfamily of ligand‐gated ion channels that mediated fast signal transmission at synapses. The present study follows up on data reported by some researchers by examining CHRNA5 polymorphisms and lung cancer risk in the population (Huang et al, ; Shen et al, ; Xu et al, ), suggesting that genetic variation in CHRNA5 may affect susceptibility to lung cancer among smokers. But, few studies have been reported in the correlation between CHRNA5 polymorphisms and schizophrenia.…”

Section: Introductionsupporting

confidence: 69%

Impact of CHRNA5 polymorphisms on the risk of schizophrenia in the Chinese Han population

Zhan¹,

Yao²,

Fu³

et al. 2019

Molec Gen & Gen Med

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Background Schizophrenia is a complex mental disease whose cause is still unknown. Neuronal nicotinic acetylcholine receptors (nAChRs) have been implicated in various neurological disorders, including schizophrenia. The previous reports have shown that CHRNA polymorphisms were involved in schizophrenia. This study is to explore the potential association between CHRNA5 (OMIM#118505) polymorphisms and schizophrenia susceptibility in a Chinese population. Methods and Results A case–control study was conducted with 384 schizophrenia patients and 687 controls. We genotyped eight single nucleotide polymorphisms (SNPs) distributed in CHRNA5. Regulome DB, HaploReg, and GTEx databases were used to calculate possible functional effects of the polymorphisms. The χ2 test, genetic model analysis, and haplotype analysis were involved in assessing genetic association between variants and schizophrenia risk. The results exhibited that rs17486278 (NC_000015.10:g.78575140A>C) was associated with a decreased risk of schizophrenia on the basis of the recessive model (adjusted OR = 0.37, 95%CI: 0.15–0.93) in females. Moreover, we found that the four variants rs588765, rs6495306, rs680244, rs692780 were extremely significant after being stratified by ≥45 years. Conclusions Overall, our findings supported that the potential association existed between CHRNA5 polymorphisms and schizophrenia susceptibility in a Chinese population. But, large sample validation is needed to enhance the accuracy of our results.

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Section: Introductionsupporting

confidence: 69%

Impact of CHRNA5 polymorphisms on the risk of schizophrenia in the Chinese Han population

Zhan¹,

Yao²,

Fu³

et al. 2019

Molec Gen & Gen Med

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“…Li et al found that the G allele of rs11072768 in CHRNB4 was significantly associated with smoking initiation (SI) (P = 0.001; OR = 1.22;95%CI: 1.08, 1.37), smoking quantity (SQ) (P = 0.016; OR = 1.16; 95%CI: 1.03, 1.31), and smoking cessation (SC) (P = 0.01; OR = 1.18; 95%CI: 1.04, 1.34) in a sample of Korean males [ 32 ]. Other studies have affirmed some SNPs (rs12914385, rs8042374 and rs588765) to be associated with smoking behaviors and are in complete agreement with an indirect link between genotypes and lung cancer[ 24 , 27 ].Nevertheless, there is much assertion that, rather than being an agent for smoking, CHRNA5-A3-B4 variants have a direct impact on lung cancer risk. Lips et al calculated a 1.2 difference in CPD due to the fact that rs16969968 homozygotes in CHRNA5 only contribute a 9% increase in lung cancer risk, which cannot account for the association between the variants, smoking behavior and lung cancer[ 31 ].…”

Section: Discussionmentioning

confidence: 68%

“…Although some previous studies confirmed an association between rs6495308 polymorphisms, smoking behaviors, and lung cancer risk, no research was conducted in China. We, therefore, examined 10 SNPs including rs6495308 (MAF (Minor Allele Frequency) > 0.1 in Asians) in CHRNA5-A3-B4 gene clusters According to the HapMap data and previous studies[ 14 , 17 , 20 , 25 – 27 ], and, after our initial results, conducted a detailed analysis of rs6495308 and rs11072768 polymorphisms, and explored whether the two SNPs have a direct or indirect effect through smoking behaviors on lung cancer using a case-control study of 1025 patients: 204 with lung cancer and 821 healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Chromosome 15q25 (CHRNA3-CHRNB4) Variation Indirectly Impacts Lung Cancer Risk in Chinese Males

Zhang

Jiang

et al. 2016

PLoS ONE

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IntroductionRecently, genome-wide association studies (GWAS) in Caucasian populations have identified an association between single nucleotide polymorphisms (SNPs) in the CHRNA5-A3-B4 nicotinic acetylcholine receptor subunit gene cluster on chromosome 15q25, lung cancer risk and smoking behaviors. However, these SNPs are rare in Asians, and there is currently no consensus on whether SNPs in CHRNA5-A3-B4 have a direct or indirect carcinogenic effect through smoking behaviors on lung cancer risk. Though some studies confirmed rs6495308 polymorphisms to be associated with smoking behaviors and lung cancer, no research was conducted in China. Using a case-control study, we decided to investigate the associations between CHRNA3 rs6495308, CHRNB4 rs11072768, smoking behaviors and lung cancer risk, as well as explore whether the two SNPs have a direct or indirect carcinogenic effect on lung cancer.MethodsA total of 1025 males were interviewed using a structured questionnaire (204 male lung cancer patients and 821 healthy men) to acquire socio-demographic status and smoking behaviors. Venous blood samples were collected to measure rs6495308 and rs11072768 gene polymorphisms. All subjects were divided into 3 groups: non-smokers, light smokers (1–15 cigarettes per day) and heavy smokers (>15 cigarettes per day).ResultsCompared to wild genotype, rs6495308 and rs11072768 variant genotypes reported smoking more cigarettes per day and a higher pack-years of smoking (P<0.05). More importantly, among smokers, both rs6495308 CT/TT and rs11072768 GT/GG had a higher risk of lung cancer compared to wild genotype without adjusting for potential confounding factors (OR = 1.36, 95%CI = 1.09–1.95; OR = 1.11, 95%CI = 1.07–1.58 respectively). Furthermore, heavy smokers with rs6495308 or rs11072768 variant genotypes have a positive interactive effect on lung cancer after adjustment for potential confounding factors (OR = 1.13, 95%CI = 1.01–3.09; OR = 1.09, 95%CI = 1.01–3.41 respectively). However, No significant associations were found between lung cancer risk and both rs6495308 and rs11072768 genotypes among non-smokers and smokers after adjusting for age, occupation, and education.ConclusionThis study confirmed both rs6495308 and rs11072768 gene polymorphisms association with smoking behaviors and had an indirect link between gene polymorphisms and lung cancer risk.

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“…CHRNA proteins are expressed in lung epithelial cells and bind nicotine, an addictive compound in cigarettes, and nitrosamines, potential lung carcinogens in cigarettes and food [17,18]. Signal transduction through CHRNA proteins was suggested to cause cell proliferation and also to facilitate neoplastic transformation.…”

Section: Discussionmentioning

confidence: 99%

The Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets

Wang

et al. 2020

Preprint

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Background To explore the mutations expression and prognostic significance of 15q25 (CHRNA5 and PSMA4) mRNA in lung adenocarcinoma (LAC) based on immunohistochemistry, TCGA and bioinformatics.Methods Mutations expression on chromosome 15q25 of 576 primary LAC patients was selected. And their survival and gene expression data were extracted from TCGA. The cell experiment about Beas-2b, A549 and H1299 cell lines were done to further prove the CHRNA5 and PSMA4 expression difference between lung cancer and normal cells. Immunohistochemistry data of CHRNA5 and PSMA4 were detected in LAC and normal tissues from 122 patients.Finally, Gene enrichment analysis (GSEA) was used to predict the regulatory genes of CHRNA5 and PSMA4.Results CHRNA5 and PSMA4 are frequently mutated in the TCGA (CHRNA5, 1.7%; PSMA4, 1.3%).The expression of CHRNA5 and PSMA4 were obviously higher in A549 and H1299 cells. Immunohistochemical staining revealed that the level of CHRNA5 and PSMA4 was considerably higher in LAC group than in normal group. There was a significant association between high expression of CHRNA5 and Smoking History (P = 0.011), Smoking History Pack Year Value(P = 0.010). Besides, there was a significant correlation between CHRNA5 and PSMA4 expression level and prognosis (P = 0.003; P = 0.008),and the higher expression, the worse prognosis. GSEA results suggested that CHRNA5 and PSMA4 high expression samples were respectively enriched to cell cycle, base excision repair, oxidative phosphorylation, protein export, aminoacyl tRNA biosynthesis etc.Conclusions The expression of CHRNA5 and PSMA4 mRNA has a significant impact on survival of LAC, they may be a potential target for treating patients with lung adenocarcinoma.

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CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

Cited by 7 publications

References 19 publications

Impact of CHRNA5 polymorphisms on the risk of schizophrenia in the Chinese Han population

Impact of CHRNA5 polymorphisms on the risk of schizophrenia in the Chinese Han population

Chromosome 15q25 (CHRNA3-CHRNB4) Variation Indirectly Impacts Lung Cancer Risk in Chinese Males

The Expression and Prognostic Significance of the Nicotinic Receptor Cluster on 15q25 about CHRNA5 and PSMA4 mRNA in Lung Adenocarcinoma Utilizing TCGA Datasets

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