Lung Cancer Susceptibility Research Articles

Potentially functional genetic variants in the TNF/TNFR signaling pathway genes predict survival of patients with non-small cell lung cancer in the PLCO cancer screening trial.

The tumor necrosis factor (TNF)/TNF receptor (TNFR) pathway is known to influence survival of patients with cancer. We hypothesize that single nucleotide polymorphisms (SNPs) in the TNF/TNFR pathway genes related to apoptosis are associated with survival of patients with non-small cell lung cancer (NSCLC). We used 1185 patients withNSCLC in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and 984 patients withNSCLC in the Harvard Lung Cancer Susceptibility Study as the discovery and validation datasets, respectively. We selected 6788 SNPs in 71 genes in the TNF/TNFR signaling pathway and extracted their genotyping data from the PLCO genowide-association study (GWAS) dataset. We performed Cox proportional hazards regression analysis to evaluate associations between the identified SNPs and survival and validated the significant SNPs, which were further analyzed for their functional relevance. We found that genotypes of two validated SNPs, IKBKAP rs4978754 CT + TT and TNFRSF1B rs677844 TC + CC, as well as their combined genotypes predicted a better overall survival (P = 0.004, 0.002 and <0.001, respectively). These two validated SNPs were predicted by the RegulomeDB score to be potentially functional. In addition, IKBKAP mRNA expression levels were significantly higher, while TNFRSF1B mRNA expression levels were significantly lower in lung cancer tissues than in adjacent normal tissues (P < 0.001). The Cancer Genome Atlas (TCGA)-based expression quantitative trait loci analysis showed that IKBKAP rs4978754 and TNFRSF1B rs677844 genotypes were significantly associated with their corresponding mRNA expression levels in lung cancer tissues in a recessive model (P = 0.035 and 0.045, respectively). Therefore, we identified two potentially functional SNPs (IKBKAP rs4978754 C > T and TNFRSF1B rs677844 T > C) to be associated with survival of patients with NSCLC.

SNPs in LncRNA genes are associated with non-small cell lung cancer in a Chinese population.

BackgroundIt has indicated that single nuclear polymorphisms (SNPs) in the regions encoding non‐coding transcripts are associated with lung cancer susceptibility. In a previous microarray study, we identified 13 differentially expressed long non‐coding RNAs (lncRNAs) in non‐small cell lung cancer (NSCLC) and associations of SNPs in these lncRNA genes with lung cancer were unknown. We conducted a case‐control study to address this issue.MethodsUsing the TaqMan method, we genotyped 17 SNPs located in the 13 lncRNA genes in 1294 cases with NSCLC and 1729 healthy controls. Unconditional logistic regression and Cox proportional hazards regression were used to analyze the associations of these SNPs with NSCLC risk and patient survival, respectively. These analyses were also repeated in subgroups of cases and controls stratified by gender, age group, smoking status, disease stage, and histological type.ResultsWe identified three SNPs associated with NSCLC risk. For SNP rs498238, CC genotype was associated with lower risk compared to TT genotype (adjusted OR = 0.33, 95%CI: 0.11‐0.97, P = 0.043). For rs16901995, CT/TT genotypes were associated with lower risk compared to CC genotype in non‐smokers (adjusted OR = 0.78, 95%CI: 0.62‐0.98, P = 0.035). Variant genotypes in rs219741 were associated with NSCLC risk in young patients, and the adjusted OR was 1.47 (95%CI: 1.03‐2.10, P = 0.033) when compared to the wild genotype. No SNPs were found to be associated with patient overall survival in the study.ConclusionThe study suggests that some genetic polymorphisms in the lncRNA genes may influence the risk of NSCLC among Chinese.

Association between IL-1R2 polymorphisms and lung cancer risk in the Chinese Han population: A case-control study.

BackgroundInterleukin‐1 receptor 2 (IL‐1R2), as an anti‐inflammatory cytokine, is involved in the pathogenesis and progression of lung cancer. However, the role of IL‐1R2 polymorphisms in patients with lung cancer has yet to be fully elucidated.MethodsSix single‐nucleotide polymorphisms (SNPs) in IL‐1R2 were genotyped in 259 patients and 346 healthy controls. We used the chi‐squared test, genetic model analysis, Haploview analysis, and multifactor dimensionality reduction (MDR) to evaluate the potential association between IL‐1R2 polymorphisms and lung cancer susceptibility. Bioinformatics analyses were conducted to analyze the expression level of IL‐1R2 and its association with the overall survival of lung cancer.ResultsOur results found that rs3218977‐GG was associated with a decreased risk of lung cancer (odds ratio [OR] = 0.39; 95% confidence interval [CI]: 0.17–0.87; p = 0.023), and rs2072472 had a significant risk‐increasing effect in the dominant model (AG + GG vs. AA: OR = 1.54; 95% CI: 1.09–2.20; p = 0.015). The MDR model also revealed that rs2072472 is the most influential risk factor of lung cancer (testing accuracy = 0.543; cross‐validation consistency = 10/10; p = 0.032). In addition, our results indicated that the IL‐1R2 mRNA level was downregulated in lung cancer patients, whereas the high expression of IL‐1R2 was related to a poor prognosis in lung cancer.ConclusionsOur results suggest that genetic variants of IL‐1R2 may play a role in lung cancer susceptibility. Further population and functional validations of our findings are warranted.

HapMap-based study: CYP2A13 may be a potential key metabolic enzyme gene in the carcinogenesis of lung cancer in non-smokers.

BackgroundThe aim of this study was to evaluate the association between CYP2A13 polymorphisms and lung cancer susceptibility using the HapMap database.MethodsA case‐control analysis of 532 subjects with lung cancer and 614 controls with no personal history of the disease was performed. The tag SNPs rs1645690 and rs8192789 for CYP2A13 were selected, and the genetic polymorphisms were confirmed experimentally through real‐time PCR, cloning, and sequencing assay.ResultsSNP frequency in this study was consistent with the HapMap Project database of Han‐Chinese and lung cancer risk was associated with CYP2A13 polymorphisms in non‐smokers. CYP2A13 shares a 93.5% identity with CYP2A6 in the amino acid sequence and the homologous sequences may interfere with the study of SNPs of CYP2A13.Conclusions CYP2A13 may be a potential key metabolic enzyme gene in the carcinogenesis of lung cancer in non‐smokers. The common polymorphisms of CYP2A13 may be candidate biomarkers for lung cancer susceptibility in Han‐Chinese.

Lung cancer family history and exposure to occupational/domestic coal combustion contribute to variations in clinicopathologic features and gene fusion patterns in non-small cell lung cancer.

BackgroundBoth genetic and environmental factors contribute to the development of cancer and its mutant spectrum. Lung cancer has familial aggregation. Lung cancer caused by non‐tobacco factors has unique pathological and molecular characteristics. The interaction between genetic lung cancer susceptibility and carcinogens from coal burning remains complex and understudied.MethodsWe selected 410 non‐small cell lung cancer (NSCLC) patients with a family history of lung cancer (FLC) and exposure to coal combustion between 2014 and 2017. Clinicopathologic parameters were analyzed. Reverse transcription‐PCR was performed to detect ALK, ROS1, RET, and NTRK1 rearrangement.ResultsAmong the 410 NSCLC patients, 192 had FLC and 204 (49.8%) were exposed to occupational or domestic coal combustion. FLC patients had the same characteristics regardless of gender and coal exposure: younger age, high female ratio, adenocarcinoma, increased metastasis, later stage at diagnosis, and higher frequency of gene fusion. Sixty‐seven patients (16.3%) had gene rearrangement: 51 (12.4%) harbored EML4‐ALK fusions and 16 ROS1 fusions (3.9%). The highest gene fusion rate (35.1%, 33/94) occurred in patients with both FLC and high tobacco and coal exposure. ALK fusions and total gene rearrangement were closely associated with women, never smokers, younger age, FLC, and coal exposure.ConclusionFLC and exposure to coal combustion have an important impact on the clinicopathological characteristics and gene fusion mode of NSCLC, particularly in cases of higher levels of carcinogens, and genetic susceptibility has a greater impact. Our findings may help evaluate the effect of FLC and coal exposure on the pathogenesis of lung cancer.

Functional polymorphisms on chromosome 5p15.33 disturb telomere biology and confer the risk of non-small cell lung cancer in Chinese population.

The chromosome 5p15.33 has been reported as a susceptibility locus for lung cancer. However, causal variants in this region have not been fully uncovered. In this study, we intended to identify functional polymorphisms associated with non-small cell lung cancer (NSCLC) susceptibility in Chinese population. A targeted sequencing on 5p15.33 region was conducted in 400 NSCLC cases. We selected candidate variants by comparing genotypic frequency with data from 1000 Genomes Project, and their associations with NSCLC were validated in 985 cases and 970 controls. The relationships between risk variants and telomere length were evaluated in 774 healthy subjects. Luciferase assays and electrophoretic mobility shift assays (EMSA) were performed to explore potential functions and reveal carcinogenic mechanisms. As a result, we identified 1478 variants through targeted sequencing and selected 17 candidates. Four polymorphisms exhibited prominent associations with lung cancer risk, including rs7726159 (OR = 1.34, 95%CI: 1.18-1.52, P = 7.78 × 10-6 ), rs10054203 (OR = 1.29, 95%CI: 1.13-1.46, P = 1.37 × 10-4 ), rs2736107 (OR = 1.28, 95%CI: 1.11-1.47, P = 5.14 × 10-4 ), and rs2853677 (OR = 1.23, 95%CI: 1.08-1.39, P = 0.002). The minor allele of rs7726159 and rs10053203 were associated with long telomeres (P = 0.008 and 0.036, respectively). Mechanistically, the rs7726159-A increased TERT transcription through mediating allele-specific MYC binding. In conclusion, the functional variant rs7726159 confers lung cancer susceptibility might by affecting MYC binding and inducing telomere lengthening, which provides a new insight into the crucial role of telomere biology in tumorigenesis.

Polymorphism in CYP24A1 Is Associated with Lung Cancer Risk: A Case-Control Study in Chinese Female Nonsmokers.

CYP24A1 plays important roles in antiproliferative effects, which have been proved in many human tumor cells. Polymorphisms in CYP24A1 may affect the risk of lung cancer, but the results remained inconclusive. To enhance the understanding of possible relationship between CYP24A1 polymorphism rs6068816 and lung cancer risks, we first carried out this case-control study among Chinese female nonsmokers, including 345 lung cancer patients and 351 noncancer controls. Our results revealed that individuals carrying CT and CC genotype were associated with decreasing lung cancer risk (adjusted odds ratios were 0.71 and 0.59, and 95% confidence intervals were 0.52-0.97 and 0.35-0.99, p-values were 0.031 and 0.048, respectively). Patients carrying allele-T showed lower hazard risks, especially in adenocarcinoma and advanced stage cancers. We also found that subjects with allele-T showed a relatively low risk of lung cancer when they were exposed to oil fume. But neither additive scale nor multiplicative scale revealed interactions between allele-T and environmental exposures, including oil fume, coal fuel fume, and passive smoking. Overall, these findings indicated that CYP24A1 polymorphism rs6068816 could be significantly associated with susceptibility of lung cancer in Chinese female nonsmokers.

Association between IL-4 tagging single nucleotide polymorphisms and the risk of lung cancer in China.

BackgroundIn China, lung cancer is also the most commonly diagnosed cancer with a lower 5‐year survival rate, leading to high social burdens. Recently, many studies highlighted the importance of inflammation in the initiation and progression of cancer. The goal of this study was to investigate the association between interleukin‐4 (IL‐4, OMIM#147780) single nucleotide polymorphisms (SNPs) and lung cancer susceptibility.MethodsA case‐control study was conducted in a Chinese population including 199 male patients with lung cancer and 266 healthy men. Six SNPs selected from the HapMap database were genotyped using Agena MassARRAY. Genetic models and haplotype analyses were utilized to evaluate the association between SNPs and lung cancer risk.ResultsIn our findings, rs2243250 was associated with a decreased lung cancer risk under the log‐additive model (odds ratio, OR = 0.71, 95% confidence interval, CI = 0.51–0.97, p = 0.030), and the G/G genotype of rs2227284 conferred a negative effect; the risk of lung cancer under the codominant (OR = 0.19, 95% CI = 0.04–0.87, p = 0.040) and recessive models (OR = 0.20, 95% CI = 0.04–0.88, p = 0.012) after adjusted by age.ConclusionsThese data indicated potential associations between IL‐4 polymorphisms and lung cancer susceptibility. That may help to improve the understanding of the relationship between inflammation and lung cancer in the future.

STAT3 rs4796793 contributes to lung cancer risk and clinical outcomes of platinum-based chemotherapy.

Signal transducer and activator of transcription (STAT) 3 plays a vital role in carcinogenesis and drug response. Platinum-based chemotherapy is the first-line treatment for lung cancer patients, especially those in advanced stages. In the present study, we investigated the association of STAT3 polymorphism rs4796793 with lung cancer susceptibility, platinum-based chemotherapy response, and toxicity. A total of 498 lung cancer patients and 213 healthy controls were enrolled in the study. 467 of them received at least 2-cycle platinum-based chemotherapy. Unconditional logistical regression analysis was used to assess the associations. STAT3 rs4769793 G allele carriers had an increased susceptibility of lung cancer [additive model: adjusted OR (95% CI) 1.376 (1.058-1.789), P = 0.017; recessive model: adjusted OR (95% CI) 1.734 (1.007-2.985), P = 0.047]. Rs4769793 was not significantly associated with platinum-based chemotherapy response in lung cancer patients. STAT3 rs4796793 was associated with an increased risk of severe overall toxicity [additive model: adjusted OR (95% CI) 1.410 (1.076-1.850), P = 0.013; dominant model: adjusted OR (95% CI) 1.638 (1.091-2.459), P = 0.017], especially hematological toxicity [additive model: adjusted OR (95% CI) 1.352 (1.001-1.826), P = 0.049]. STAT3 rs4796793 may be considered as a potential candidate biomarker for the prediction of susceptibility and prognosis in Chinese lung cancer patients. However, well-designed studies with larger sample sizes are required to verify the results.

Genome-wide analysis of expression quantitative trait loci identified potential lung cancer susceptibility variants among Asian populations

Even though genome-wide association studies (GWASs) have identified dozens of single nucleotide polymorphisms (SNPs) affecting the susceptibility to lung cancer, only a tiny fraction of heritability can be explained. Regulating the expression of surrounding genes is one of the important mechanisms for SNPs to exert their effect. So it is necessary to systematically evaluate the associations between expression quantitative trait loci (eQTL) and lung cancer risk. In this study, a two-stage case-control design was used to evaluate the associations of eQTL SNPs (eSNPs) defined by GTEx in normal lung tissues with the risk of lung cancer based on two GWAS datasets, including 7127 cases and 6818 controls. Promising variants were replicated in an independent population with 1026 lung cancer cases and 1006 controls. Functional annotations of the identified eSNPs and related genes were performed based on multiple public databases. Finally, we identified two potential eSNPs associated with the risk of lung cancer in 3q28 [rs505974, OR = 0.90 (0.86 - 0.94), P = 6.51 × 10-6] and 21q22.3 [rs79589812, OR = 1.38 (1.21 - 1.58), P = 2.46 × 10-6]. Subgroup analysis showed rs505974 might interact with smoking behaviour. Gene-set enrichment and pathway analysis revealed that rs505974 may affect the susceptibility to lung cancer via regulating the expression of CLDN16, which may be involved in the chemical carcinogenesis pathway, whereas rs79589812 may regulate the expression of SPATC1L, which may be involved in the base excision repair pathway. These results provide an overview of the associations between eSNPs and lung cancer in Asian populations.

Systematic analyses of regulatory variants in DNase I hypersensitive sites identified two novel lung cancer susceptibility loci.

DNase I hypersensitive sites (DHS) are abundant in regulatory elements, such as promoter, enhancer and transcription factor binding sites. Many studies have revealed that disease-associated variants were concentrated in DHS-related regions. However, limited studies are available on the roles of DHS-related variants in lung cancer. In this study, we performed a large-scale case-control study with 20 871 lung cancer cases and 15 971 controls to evaluate the associations between regulatory genetic variants in DHS and lung cancer susceptibility. The expression quantitative trait loci (eQTL) analysis and pathway-enrichment analysis were performed to identify the possible target genes and pathways. In addition, we performed motif-based analysis to explore the lung-cancer-related motifs using sequence kernel association test. Two novel variants, rs186332 in 20q13.3 (C>T, odds ratio [OR] = 1.17, 95% confidence interval [95% CI]: 1.10-1.24, P = 8.45 × 10-7) and rs4839323 in 1p13.2 (T>C, OR = 0.92, 95% CI: 0.89-0.95, P = 1.02 × 10-6) showed significant association with lung cancer risk. The eQTL analysis suggested that these two SNPs might regulate the expression of MRGBP and SLC16A1, respectively. What's more, the expression of both MRGBP and SLC16A1 was aberrantly elevated in lung tumor tissues. The motif-based analysis identified 10 motifs related to the risk of lung cancer (P < 1.71 × 10-4). Our findings suggested that variants in DHS might modify lung cancer susceptibility through regulating the expression of surrounding genes. This study provided us a deeper insight into the roles of DHS-related genetic variants for lung cancer.

Single nucleotide polymorphism in the 3\u2032 untranslated region of LPP is a risk factor for lung cancer: a case-control study

BackgroundSingle nucleotide polymorphisms (SNPs) in 3′-untranslated region (UTR) of genes related with cell-matrix adhesions and migration might affect miRNA binding and potentially affect the risk of cancer. The present study aimed to screen SNPs in 3′ UTR of cancer-related genes and investigate their contribution to the susceptibility of lung cancer.MethodsSeven SNPs were selected and genotyped in a case-control study (322 lung cancer patients and 384 controls) among Chinese Han population. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by logistic regression adjusted for age and gender in multiple genetic models.ResultsIn stratified analyses by gender, three (rs1064607, rs3796283 and rs2378456) of LPP gene were associated with a significantly increased susceptibility for lung cancer among male population. Besides, LPP rs2378456 weakened lung cancer risk in female. LPP rs1064607 polymorphism was significantly correlated with increased risk of lung adenocarcinoma. Furthermore, AA genotype of TNS3 rs9876 polymorphism was associated with lymphatic metastasis.ConclusionOur results provides evidence for the impact of LPP polymorphisms on the susceptibility to lung cancer in Chinese population.

Integrative system genetic analysis reveals mRNA-lncRNA network associated with mouse spontaneous lung cancer susceptibility.

IntroductionLung cancer continues to be a significant health burden in the United States. Lung cancer in never smokers is considered as a different disease and underlying mechanism of spontaneous lung cancer susceptibility is still poorly known. Meanwhile, the roles of long non-coding RNAs (lncRNAs), which have multiple functions in biological processes, have seldom been studied in spontaneous lung cancer susceptibility.MethodsIn this study, microarray analyses of normal lung tissues were performed in 23 different mouse strains. LncRNA profile was analyzed by re-annotating exon array for lncRNAs detection. LncRNA/mRNA co-expression networks were constructed and the association between significant lncRNA module and significant mRNA modules was calculated. Finally, Genome-wide association (GWA) results were used to further highlight the key mRNAs and lncRNAs associated with spontaneous lung cancer susceptibility.ResultsFour mRNA modules were significantly associated with spontaneous lung cancer susceptibility. Genes in these modules were enriched in “blood coagulation” and “immune system process”. Only one lncRNA module was significantly associated with spontaneous lung cancer susceptibility. Many lncRNAs in this module were co-expressed with mRNAs in the second most significant mRNA module. This co-expression network contained 113 interactions between 30 lncRNAs and 40 mRNAs. After GWA filtration, two mRNAs (Myo7a and Zfp874a) and two lncRNAs (n290048 and n271850) were highlighted as the candidates responsible for genetic susceptibility to lung cancer.ConclusionsWe firstly used integrative system genetic analysis to report the mRNA-lncRNA network associated with spontaneous lung cancer susceptibility and identified potential targets for lung cancer prevention.

Methylenetetrahydrofolate Reductase (MTHFR) Gene rs1801133 C&gt;T Polymorphisms and Lung Cancer Susceptibility: An Updated Meta-analysis

Abstract Objective: The aim of this study was to investigate the methylenetetrahydrofolate reductase (MTHFR) gene rs1801133 C&gt;T polymorphisms and lung cancer susceptibility by pooling openly published data. Methods: Electronic databases of Medline, Web of Science, Embase, Google scholar, CBM and CNKI were systematic searched to find the relevant studies related to MTHFR gene rs1801133 C&gt;T polymorphisms and lung cancer susceptibility. The odds of TT, CT and CC alleles in lung cancer patients compared with healthy controls was pooled by the effect size of odds ratio (OR) and corresponding 95% confidence interval (95%CI) under random or fixed effect model. Publication bias was analyzed by Begg’s funnel plot and Egger’s line regression test. Results: Overall, twenty-one studies relevant to MTHFR gene rs1801133 C&gt;T polymorphisms and lung cancer susceptibility were included. The pooled data showed subject with T allele had significant increased risk of developing lung cancer in dominant (OR=1.14, 95%CI: 1.01-1.28, p&lt;0.05), recessive (OR=1.26, 95%CI:1.08-1.48, p&lt;0.01) and homologous (OR=1.36, 95%CI:1.12-1.65, p&lt;0.01) genetic model. Begg’s funnel plot and Egger’s line regression test showed significant publication bias in all genetic models. Conclusion: Based on present data, subjects with TT or CT alleles may have increased susceptibility to lung cancer. However, due to significant publication bias, the conclusion should be drawn with caution and should be proved by further well-designed case-control or cohort studies relevant to MTHFR gene rs1801133 C&gt;T polymorphisms and lung cancer risk.

Fine Mapping in Chromosome 3q28 Identified Two Variants Associated with Lung Cancer Risk in Asian Population.

Genome-wide association studies (GWASs) have consistently identified chromosome 3q28 as a lung cancer susceptibility region. To further characterize the potential genetic mechanism of the variants in this region, we conducted a fine-mapping study on chromosome 3q28 region. We performed a target resequencing in 200 lung cancer cases and 300 controls in the screening and followed by validation in multi-ethnic lung cancer GWASs with 12,843 cases and 12,639 controls. For our identified novel variants, we conducted expression quantitative trait loci (eQTL) analysis to reveal the potential target genes. Two susceptibility variants were identified (rs4396880: G>A, OR = 0.35, 95%CI: 0.20-0.62, P = 3.01×10-4; and rs3856776: C>T, OR = 2.05, 95%CI: 1.32-3.18, P = 1.49×10-3) and further supported in Asian population (rs4396880: OR = 0.88, P = 7.43×10-6; and rs3856776: OR =1.17, P = 1.64×10-4). The eQTL analysis showed the A allele of rs4396880 was significantly associated with higher mRNA expression of TP63 (P = 1.70×10-4) in lung tissues, while rs3856776 showed significant association with the expression of LEPREL1-AS1 (P = 6.90×10-3), which was the antisense RNA of LEPREL1 and could suppress the translation of LEPREL1. Notably, LEPREL1 was aberrantly downregulated (P = 2.54×10-18) in lung tumor tissues based on TCGA database. In conclusion, this is the first fine-mapping analysis of 3q28 region in Han Chinese, and we found two variants associated with lung cancer susceptibility in Asian population. What's more, rs3856776 was newly identified and might modulate lung cancer susceptibility by suppressing the function of LEPREL1.

The association of matrix metalloproteinas-2 promoter polymorphisms with lung cancer susceptibility in Taiwan.

Matrix metalloproteinases-2 (MMP2) has been reported to be overexpressed in various types of cancer. However, the contribution of various genotypes of MMP2 to lung cancer is controversial and not yet been examined in Taiwan. Therefore, in the current study, we investigated the association of MMP2 genotypes with lung cancer risk among Taiwanese. In this hospital-based, case-control study, 358 lung cancer patients and 716 age- and gender-matched healthy controls were recruited, and the genotypic distributions of MMP2-1306 and MMP2- 735 were determined. Then, their association with lung cancer was evaluated, and their interaction with personal smoking status was also examined via stratification analysis. The results showed that the percentages of variant CT and TT at MMP2-1306 were 17.3% and 1.7% among the lung cancer patients, respectively, much lower than those of 28.7% and 2.4%, respectively, among the healthy controls (P for trend = 0.0001). The allelic frequency distribution analysis showed that the variant T allele at MMP2-1306 conferred a statistically significantly lower lung cancer risk than the wild-type C allele (adjusted odds ratio = 0.54, 95% confidence interval = 0.41-0.72, P = 0.0001). There was an obvious effect of MMP2-1306 genotype on lung cancer risk among the subpopulations of ever smokers but not nonsmokers. As for the genotypes of MMP2-735, there was no such differential distribution in the aspects of genotypic or allelic frequencies, or combinative effects with smoking status. The genotypes of MMP2-1306 may act as a biomarker in determining personal susceptibility to lung cancer in Taiwan. The contribution of MMP2 genotypes alone and its joint effects with personal cigarette smoking habit on lung cancer susceptibility should be taken into consideration of the clinical practices for early detection and prediction of lung cancer in Taiwan.

Correlations between angiopoietin-2 gene polymorphisms and lung cancer progression in a Chinese Han population.

Lung cancer is the most common malignancy in China and is associated with a poor survival rate amongst Han Chinese. The high mortality is largely attributed to late-stage diagnosis, when treatment is largely ineffective. Identification of genetic variants could potentially assist with earlier diagnosis and thus more effective treatment. The development and progression of lung cancer is stimulated by angiopoietin-2 (Ang2), a ligand for Tie2, an endothelial tyrosine kinase. Patients with lung cancer with higher serum Ang2 levels have significantly poorer survival than patients with lower serum Ang2 levels. We explored the effects of Ang2 single nucleotide polymorphisms (SNPs) on lung cancer susceptibility. We used lung cancer tissue and serum samples to measure Ang2 expression in a Chinese Han population. Five Ang2 SNPs (rs2442598, rs734701, rs1823375, 11137037, and rs12674822) were analyzed using TaqMan SNP genotyping in 695 patients with lung cancer and 900 cancer-free controls. Carriers of the variant GT allele of rs12674822 had a higher risk of lung cancer than wild-type (GG) carriers, while the presence of the CC genotype at rs11137037 was associated with higher clinical stage disease compared with having the AA genotype. Our study is the first to document a correlation between Ang2 polymorphisms and lung cancer development and progression in people of Chinese Han ethnicity.

Association between p73 gene G4C14-to-A4T14 polymorphism and risk of lung cancer: A meta-analysis.

To explore the correlation between p73 G4C14-to-A4T14 polymorphism and lung cancer risk. The meta analysis was conducted from October 2017 to March 2018, and comprised studies published till March 27, 2018, that addressed the relationship between the p73 G4C14-to-A4T14 polymorphism and risk of lung cancer, and were available on databases including PubMed, Web of Science, Embase, Cochrane Library and China National Knowledge Infrastructure. Pooled odds ratio with corresponding 95% confidence interval and subgroup analysis between ethnicities were carried out to assess the association between the two parameters using four different models. Stata 12 was used for data analysis. For overall population, there was no significant risk of lung cancer for the polymorphism under allele and dominant genetic models. However, reduced risks were found under homozygous (AT/AT vs GC/GC; p=0.02) and recessive (AT/AT vs GC/AT + GC/GC; p=0.02) comparison models. Subgroup analysis between ethnicities demonstrated reduced risk of lung cancer for the polymorphism under the four genetic comparison models for Asian population, but increased risk for the Caucasian group. AT/AT variant carriers possessed reduced susceptibility of lung cancer in the general population. Ethnic differences for the p73 gene polymorphism played an important role in lung cancer susceptibility.

Association between Polymorphisms of Vitamin D Receptor and Lung Cancer Susceptibility: Evidence from an Updated Meta-analysis.

Purpose: The aim of this meta-analysis was to investigate polymorphism of Bsm1, Apal, Taq1 and Cdx-2 in vitamin D receptor (VDR) associations in relation to lung cancer (LC) susceptibility.Methods: 9 literatures were recruited into this meta-analysis from PubMed, PMC, Embase, Web of Science, Cochrane library and CNKI. STATA version 15.1 was used for statistical tests. The heterogeneity was tested using I2 statistics. According to the value of I2, the random-effect model (REM) or fixed-effect model (FEM) was selected to combine data from studies, respectively. Potential publication bias was evaluated by Egger's test. Sensitivity analysis was also performed to evaluate the stability and reliability in results.Results: Decreased susceptibility of LC was found in all genetic models contrast in Bsm1 gene of VDR (a vs. A: OR = 0.62, 95 % CI = 0.44-0.87; aa vs. AA: OR = 0.76, 95 % CI = 0.60-0.96; Aa vs. AA: OR = 0.59, 95 % CI = 0.39-0.88; aa vs. AA+Aa: OR = 0.80, 95 % CI = 0.64-0.99; Aa+aa vs. AA: OR = 0.57, 95 % CI = 0.37-0.86). The similar results were also found in partial genetic models of Taq1 (a vs. A: OR = 0.88, 95 % CI = 0.79-0.98; aa vs. AA+Aa: OR = 0.84, 95 % CI = 0.73-0.98) and Cdx-2 (Aa vs. AA: OR = 0.80, 95 % CI = 0.66-0.98; Aa+aa vs. AA: OR = 0.79, 95 % CI = 0.65-0.96). Likewise, significant correlation between Bsm1, Taq1 polymorphism and LC risk was detected among Asians. Cdx-2 polymorphism was considered as a protective factor in Caucasians, whereas no association of Apal polymorphism with LC risk was observed in Asians and Caucasians for all genetic models.Conclusion: The results of this meta-analysis suggested that Bsm1, Taq1 and Cdx-2 polymorphism may contribute to lung cancer susceptibility, more studies need be conducted to confirm in the future.

The Impact of IL-16 3'UTR Polymorphism rs859 on Lung Carcinoma Susceptibility among Chinese Han Individuals.

Lung carcinoma is the most common cancer and cause of cancer deaths among both males and females in China. Previously, genetic variants located in gene untranslated region have been well established as interfering factors in mRNA translation and confirmed playing critical roles in lung oncogenesis. However, the correlation between polymorphisms in gene 3′ untranslated region and lung cancer risk is less reported in China Han population. In this study, polymorphisms in 3′-untranslated region of IL-16, CYP24A1, and FBN1 were determined in 322 lung cancer patients and 384 healthy controls with the usage of Sequenom MassARRAY. The correlation between selected variants and lung cancer risk was examined by unconditional logistic regression analysis with or without adjustments for age, gender, smoking status, and alcohol drinking status. Additionally, stratification analysis was applied to detect the associations of SNPs with lung cancer in different subgroups. As the results, significant relationships were found between IL-16 rs859 and lung cancer susceptibility in recessive model (OR= 0.65, 95% CI: 0.44-0.96, P= 0.029) and log-additive model (OR= 0.76, 95% CI: 0.60-0.96, P= 0.019). Moreover, adjusted stratified analysis also revealed the important effects of IL-16 rs859 on lung cancer risk among individuals aged older than 50, males, and nondrinkers. IL-16 rs859 showed statistically significant evidence associated with susceptibility to lung adenocarcinoma and lung small cell carcinoma in Chinese Han population as well. Our research demonstrated that genetic variant rs859 of IL-16 3′UTR was associated with lung cancer risk in Chinese Han population and the result might be exploited as a new biomarker for lung cancer assessment and prevention.