Association Between ERCC2 Lys751Gln Polymorphism and Lung Cancer Risk: A Meta-Analysis Involving 23,370 Subjects

2014 ◽  
Vol 17 (2) ◽  
pp. 99-107 ◽  
Author(s):  
Xiang Tan ◽  
Lei Xian ◽  
Xinyu Chen ◽  
Lijun Shi ◽  
Yongyong Wang ◽  
...  

Recent studies report a correlation between excision repair cross-complementing group 2 (ERCC2) Lys751Gln polymorphism and an increased risk of lung cancer, but results are controversial and inconclusive. Thus, we conducted a comprehensive meta-analysis in order to assess the correlation between them. Our study uses an odds ratio (OR) with a 95% confidence interval (95% CI) to evaluate the strength of the association; we also performed Begg's funnel plot and the Egger's test to assess the publication bias of previous articles. Finally, our meta-analysis is comprised of 28 full studies, including 23,370 subjects (10,242 cases and 13,128 controls). Our overall research shows that ERCC2 Lys751Gln polymorphism carries an increased risk of developing lung cancer (C vs. A: OR = 1.160, 95% CI = 1.081–1.245, p = .000; CC vs. AA: OR = 1.252, 95% CI = 1.130–1.388, p = .000; CA vs. AA: OR = 1.152, 95% CI = 1.060–1.252, p = .001; CC+CA vs. AA: OR = 1.186, 95% CI = 1.089–1.292, p = .000; CC vs. CA+AA: OR = 1.196, 95% CI = 1.087–1.316, p = .000). In ethnic subgroup analyses, we find a significant risk among Caucasians (C vs. A: OR = 1.106, 95% CI = 1.048–1.166, p = .000; CC vs. AA: OR = 1.233, 95% CI = 1.103–1.378, p = .000; CC+CA vs. AA: OR = 1.113, 95% CI = 1.033–1.199, p = .005; CC vs. CA+AA: OR = 1.185, 95% CI = 1.069–1.313, p = .001) and among Asians under two genetic models (CA vs. AA: OR = 1.265, 95% CI = 1.034–1.549, p = .023; CC+CA vs. AA: OR = 1.252, 95% CI = 1.015–1.544, p = .036). These results were confirmed by similar findings, demonstrated by stratified analyses in study design and histological typing. This meta-analysis indicates that ERCC2 Lys751Gln polymorphism may lead to an increased susceptibility to lung cancer risk among Caucasians and Asians.

2010 ◽  
Vol 2010 ◽  
pp. 1-17 ◽  
Author(s):  
Chikako Kiyohara ◽  
Koichi Takayama ◽  
Yoichi Nakanishi

Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We conducted a meta-analysis of epidemiologic studies on the association between genetic polymorphisms in both base excision repair and nucleotide excision repair pathways, and lung cancer. We found xeroderma pigmentosum complementation group A (XPA) G23A (odds ratio (OR)=0.76, 95% confidence interval (CI)=0.61–0.94), 8-oxoguanine DNA glycosylase 1 (OGG1) Ser326Cys (OR=1.22, 95% CI=1.02–1.45), and excision repair cross-complementing group 2 (ERCC2) Lys751Gln (OR=1.27, 95% CI=1.10–1.46) polymorphisms were associated with lung cancer risk. Considering the data available, it can be conjectured that if there is any risk association between a single SNP and lung cancer, the risk fluctuation will probably be minimal. Advances in the identification of new polymorphisms and in high-throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples of cases and controls.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ke Zhu ◽  
Aiqun Xu ◽  
Wanli Xia ◽  
Pulin Li ◽  
Binbin Zhang ◽  
...  

Lung cancer is the leading cause of cancer-related death worldwide and has a high incidence rate. N-Acetyltransferase 2 (NAT2) is a polymorphic xenobiotic enzyme, which can catalyze N-acetylation and O-acetylation of various carcinogens such as aromatic, heterocyclic amines and hydrazines. At present, many studies have explored the effects of NAT2 polymorphism on lung cancer, but we found inconsistent results. We researched 18 published studies, involving 4,016 patients and 5,469 controls, to more accurately assess the effects of NAT2 polymorphism on lung cancer risk and to investigate whether smoking is associated. We used STATA software to analyze the extracted data and used STATA for subgroup analysis, sensitivity analysis, and to perform publication bias tests. To determine the correlation, we used the crude odds ratio (ORs) with 95% confidence interval (CIs). Our study was prospectively registered in PROSPERO (CRD42020159737). The odds ratio was 1.53 (95% CI: 1.21–1.95, I² = 45.2%, P=0.104) for the NAT2 slow + intermediate phenotype versus rapid phenotype. The results suggested that people with NAT2 non-rapid (slow + intermediate) phenotype have a significantly increased risk of lung cancer. In addition, NAT2 rapid phenotype was significantly associated with reduced risk of lung cancer, compared with slow phenotype or intermediate phenotype (slow phenotype vs. rapid phenotype: OR: 1.61, 95% CI: 1.07–2.42, I²= 50%, P= 0.075; intermediate phenotype vs. rapid phenotype: OR: 1.47, 95% CI: 1.15–1.88, I²= 40.3%, P= 0.137).


2019 ◽  
Vol 21 (10) ◽  
pp. 704-710 ◽  
Author(s):  
Zhi-Hong Yu ◽  
Miao Chen ◽  
Qing-Qian Zhang ◽  
Xun Hu

The association between vitamin D receptor (VDR) genetic polymorphism and lung cancer risk has been evaluated by the previous meta-analyses. Due to the emergence of novel studies and inappropriate inclusion of overlapping populations, an updated meta-analysis on recent evidences is necessarily needed. We comprehensively searched databases of PubMed, Web of Science and Chinese National Knowledge Infrastructure and finally obtained 7 eligible studies according to the inclusion criteria. Four positions on VDR gene, namely ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810) and TaqI (rs731236), were considered in this investigation. Data pooling found no significant association of lung cancer risk with ApaI or FokI. In contrast, it was indicated that the BsmI A allele was negatively related to the lung cancer risk, compared with the G allele (OR = 0.51, 95% CI = 0.33-0.79). Individuals with BsmI AA (OR = 0.53, 95% CI = 0.26-1.11) and AG genotypes (OR = 0.46, 95% CI = 0.30−0.71) showed decreased risk of lung cancer, compared with those of GG genotype. Regarding the TaqI polymorphism, the T allele carriers were at increased risk of lung cancer (OR = 1.25, 95% CI = 1.04-1.50). Compared with the TaqI TC+CC genotype, the TT genotype was positively associated with lung cancer risk (OR = 1.42, 95% CI = 1.11-1.82). No publication bias was identified in any of the analysis. In conclusion, VDR genetic polymorphism may be correlated to lung cancer risk. Given limited number of the included studies, more observations are warranted to draw a safer conclusion.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hui Zeng ◽  
Zhuoyu Yang ◽  
Jiang Li ◽  
Yan Wen ◽  
Zheng Wu ◽  
...  

Abstract Background Published findings suggest sex differences in lung cancer risk and a potential role for sex steroid hormones. Our aim was to perform a meta-analysis to investigate the effects of sex steroid hormone exposure specifically on the risk of lung cancer in women. Methods The PubMed, MEDLINE, Web of Science, and EMBASE databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for female lung cancer risk associated with sex steroid hormones were calculated overall and by study design, publication year, population, and smoking status. Sensitivity analysis, publication bias, and subgroup analysis were performed. Results Forty-eight studies published between 1987 and 2019 were included in the study with a total of 31,592 female lung cancer cases and 1,416,320 subjects without lung cancer. Overall, higher levels of sex steroid hormones, both endogenous (OR: 0.92, 95% CI: 0.87–0.98) and exogenous (OR: 0.86, 95% CI: 0.80–0.93), significantly decreased the risk of female lung cancer by 10% (OR: 0.90, 95% CI: 0.86–0.95). The risk of lung cancer decreased more significantly with a higher level of sex steroid hormones in non-smoking women (OR: 0.88, 95% CI: 0.78–0.99) than in smoking women (OR: 0.98, 95% CI: 0.77–1.03), especially in Asia women (OR: 0.84, 95% CI: 0.74–0.96). Conclusions Our meta-analysis reveals an association between higher levels of sex steroid hormone exposure and the decreased risk of female lung cancer. Surveillance of sex steroid hormones might be used for identifying populations at high risk for lung cancer, especially among non-smoking women.


2019 ◽  
Vol 166 (4) ◽  
pp. 323-329 ◽  
Author(s):  
Randa H Mohamed ◽  
Heba F Pasha ◽  
Doaa M Gad ◽  
Mostafa M Toam

AbstractRecently, MicroRNAs polymorphisms and their serum expression have been linked to increase risk of various cancers. The aim of this study was to elucidate the association between single nucleotide polymorphisms of miR-146a and miR-196a-2 and their serum expression and lung cancer risk. One hundred and twenty lung cancer patients and 120 health controls were included in this study. Genotyping and expression for miR-146a and miR-196a-2 were performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and quantitative real-time PCR. Individuals carrying miR-146a CG and CC genotypes had significantly increased risk for lung cancer than those carrying miR-146a GG genotype. MiR-146a expression significantly decreased in miR-146a CG and CC genotypes carriers as compared with GG genotype carriers. MiR-196a-2 CT and TT genotypes were significantly associated with increased lung cancer while the highest expression of MiR-196a-2 was detected in miR-196a-2 CC genotype carriers. Serum miR-146a was significantly decreased in lung cancer patients while serum miR-196a-2 expression was significantly increased in lung cancer patients. In conclusion, miR-146a and miR-196a-2 genes polymorphisms and their circulating levels were associated with lung cancer risk in Egyptians and may be helpful in early detection of lung cancer.


2000 ◽  
Vol 21 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Monica Neri ◽  
Elio Geido ◽  
Rosangela Filiberti ◽  
Roberto Orecchia ◽  
Angela Di Vinci ◽  
...  

The glycophoryn A (GPA) assay evaluates somaticin vivomutations. It is considered a cumulative biodosimeter for genotoxic exposures and is under evaluation in cancer risk assessment.GPA, a polymorphic membrane protein of the erythrocytes, determines the MN blood groups. The N0 and NN variant frequencies (VF) may be detected in MN subjects (about 50% of the population) by flow cytometry using two differently labelled antibodies.We explored if GPA N0 and NN VF might be relevant to the assessment of individual lung cancer risk and susceptibility, in a small population with a high prevalence of heavy tobacco smokers: 8 lung cancer patients and 16 subjects with non‐malignant lung diseases associated with increased risk of lung cancer.There was a wide interindividual variability and complete overlap between non‐neoplastic and neoplastic patients. A significant positive correlation was seen with smoking duration in N0 VF (p=0.04, age‐adjusted). Current smokers (n=12) displayed higher N0 values than never (n=1) or ex‐smokers (n=11), 36.3±18.2 and 21.0±13.2, respectively (p< 0:01). No association was shown with occupational exposure.The present exploratory study suggests that assessment of individual lung cancer risk and susceptibility by the GPA assay does not seem to be feasible. The assay appears to provide a biomarker of longterm exposure to tobacco smoke.


2015 ◽  
Vol 15 (23) ◽  
pp. 10325-10328 ◽  
Author(s):  
Ying-Ze Huang ◽  
Wei Wu ◽  
Kun Wu ◽  
Xiao-Ning Xu ◽  
Wen-Ru Tang

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