Lung Cancer In Asian Population Research Articles

First-Line Anaplastic Lymphoma Kinase (ALK) Inhibitors for ALK-Positive Lung Cancer in Asian Populations: Systematic Review and Network Meta-Analysis.

Various anaplastic lymphoma kinase inhibitors (ALKIs) have been approved for first-line use in treating anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). To date, no head-to-head comparison of these newer generation ALKIs has been made, and different efficacies of ALKIs may present across ethnicity. This study aims to compare newer generation ALKIs for treatment efficacy in Asian groups using network meta-analysis. Phase II/III trials that enrolled treatment-naïve Asian ALK-rearranged NSCLC patients treated by ALKIs were included. Progression-free survival (PFS) and overall response rate (ORR) of each trial were extracted as indicators of drug efficacy. Surfaces under cumulative ranking curves (SUCRAs) were calculated as a numeric presentation of the overall ranking associated with each agent. After a systematic literature review, six phase III clinical trials were included. Our results showed that newer generation ALKIs, such as alectinib, brigatinib, ensartinib, and lorlatinib, all demonstrated superior efficacy to crizotinib. Among those, ensartinib exhibited the best overall SUCRA value and ranked first among all agents. According to our network meta-analysis, ensartinib may currently be the most effective first-line treatment for Asian patients with ALK-positive NSCLC. However, this conclusion needs further validation by a larger scale of clinical trials or posthoc analysis of Asian populations. Moreover, in our comparison, low-dose alectinib (300 mg twice daily) exhibited an efficacy profile similar to a higher dose regimen in Asian populations.

Screening rate and influential factors of lung cancer with low-dose computed tomography in Asian population: a systematic review and meta-analysis

There are currently no studies synthesizing the screening rate and influential factors of low-dose computed tomography (LDCT)-screened lung cancer in Asian population. A systematic review was conducted, using both English and Chinese language databases on March, 2019. The pooled screening rate and estimated odds ratios (ORs) of influential factors were analyzed using random effects models. Subgroup and meta-regression analyses were also employed to explore the heterogeneity. The pooled LDCT lung cancer screening rate was 1.12% (95% confidence interval (CI): 0.94%, 1.32%), and increased with age. Adenocarcinoma and stage I lung cancer had higher screening rates. Analysis of influential factors in the general population showed that female and elder age (≥50years) were significantly influencing LDCT lung cancer screening rate (for female, OR = 1.32, 95% CI: 1.15-1.52; for adults ≥ 50years, OR = 1.94, 95% CI: 1.52-2.49). Meta-regression analysis indicated that the heterogeneity maybe significantly correlated with the sample size, risk population and source of population. Unlike European and American populations, female and adults > 50years rather than smoking adults were positively associated with screening rate in Asian populations. It is important to further study the benefits of lung cancer screening with LDCT in Asian populations.

A cohort study on the association of MDM2 SNP309 with lung cancer risk in Bangladeshi population.

Background/AimsBangladesh is a densely populated country with an increased incidence of lung cancer, mostly due to smoking. Therefore, elucidating the association of mouse double minute 2 homolog (MDM2) single nucleotide polymorphism (SNP) 309 (rs2279744) with lung cancer risk from smoking in Bangladeshi population has become necessary.MethodsDNA was extracted from blood samples of 126 lung cancer patient and 133 healthy controls. The MDM2 SNP309 was genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), using the restriction enzymes MspA1I. Logistic regression was then carried out to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the risk of lung cancer. A meta-analysis of SNP309 was also carried out on 12,758 control subjects and 11,638 patient subjects.ResultsIn multivariate logistic regression, significantly increased risk of lung cancer was observed for MDM2 SNP309 in the dominant model (TG + GG vs. TT: OR, 2.13; 95% CI, 1.29 to 3.53). Stratification analysis revealed that age, sex, obesity, and smoking also increases the risk of lung cancer when carrying the MDM2 SNP309. Our meta-analysis revealed that MDM2 SNP309 was considerably associated with lung cancer in Asian populations (TG + GG vs. TT: OR, 1.32; 95% CI , 1.12 to 1.56; p = 0.019 for heterogeneity).ConclusionsThe MDM2 SNP309 was associated with high risk of lung cancer in Bangladeshi and Asian population, particularly with increased age, smoking, and body mass index.

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.

Patient factors to consider before lung cancer screening.

We would like to appreciate Dr. Fan and Dr. Liu for bringing up an important issue about who should be screened for lung cancer in Asian population through their editorial entitled “ Lung cancer screening using low dose CT: screening population and positive results definition ” (1).

IL-10 -1082A/G, -592C/A, and -819T/C polymorphisms in association with lung cancer susceptibility: a meta-analysis.

Numerous studies have examined the association between interleukin-10 (IL-10 -1082A/G, -592C/A, and -819T/C) gene polymorphisms and risk of lung cancer, but these have revealed inconsistent results. The aim of this study was to clarify the relationship between these polymorphisms and the risk of lung cancer by performing a meta-analysis. The published literature concerning IL-10 polymorphisms and lung cancer risk were retrieved by systematically searching PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang, and Database of Chinese Scientific and Technical Periodicals (VIP) database. Statistical analysis was conducted with Stata 12.0 software. A total of ten published articles comprising of 19 studies were selected, including seven studies (1,960 controls and 1,321 cases) for IL-10 -1082A/G, seven studies (2,613 controls and 1,839 cases) for IL-10 -592C/A, and five studies (1,558 controls and 926 cases) for IL-10 -819T/C. This study found that the IL-10 -1082A/G and -592C/A polymorphisms were significantly associated with the risk of lung cancer in the overall analysis. When stratified by ethnicity, significantly increased risks were observed for IL-10 -1082A/G, -592C/A, and -819T/C polymorphisms in Asians (for -1082A/G, AA vs [AG + GG]: odds ratio [OR] =1.20, confidence interval [CI] =1.05–1.39, P<0.05; for C-592A, C vs A, OR =1.36, CI =1.20–1.53, P<0.05; CC vs AA, OR =1.85, CI =1.45–2.37, P<0.05; CC vs [CA + AA], OR =1.36, CI =1.15–1.61, P<0.05; for -819T/C, T vs C: OR =1.21, CI =1.06–1.38, P<0.05; TT vs CC, OR =1.54, CI =1.18–2.01, P<0.05; [TT + TC] vs CC, OR =1.51, CI =1.17–1.95, P<0.05). Moreover, the data indicated that there was a significant association between IL-10 -819T/C polymorphism and non-small-cell lung cancer risk. No significant publication bias was detected under the four genetic models (allele model, homozygous model, dominant model, and recessive model) in this meta-analysis. On the basis of these 19 studies, this study found that the IL-10 -1082A/G and -819T/C polymorphisms might have a significant association with risk of lung cancer in Asian populations.

Strong evidence for LncRNA ZNRD1-AS1, and its functional Cis- eQTL locus contributing more to the susceptibility of lung cancer.

Long noncoding RNAs (IncRNAs), involved in cancer biology, contributing to essential cancer cell functions such as proliferation, invasion, and metastasis, have received increasing attention recently. Human Zinc ribbon domain containing 1 (ZNRD1) has been confirmed to be involved in carcinogenesis and development of multiple cancers. ZNRD1-AS1, a lncRNA in the upstream region of ZNRD1 which could down-regulate the expression of ZNRD1, has been identified as a possible component in carcinogenesis. The underlying relations of ZNRD1-AS1 with lung cancer development and metastasis remain obscure. In current study, we first evaluated the expression ZNRD1-AS1 and ZNRD1 among lung cancer tissues and corresponding normal tissues, which showed higher expression of ZNRD1-AS1 and lower expression of ZNRD1. To reveal the underlying mechanisms, we then investigated the associations between ZNRD1 eQTLs SNPs in ZNRD1-AS1 and risk of lung cancer in Han Chinese populations. G allele of SNP rs9261204 was significantly associated with an increased risk of lung cancer when compared with A allele (OR: 1.45; 95% CI: 1.19–1.75; P = 1.06 × 10−4). A weaker, but similar effect was also observed in bladder cancer. SNP rs3757328 was also associated with increased risk of lung cancer (OR: 1.34; 95% CI: 1.07–1.67; P = 0.011). Our findings first confirmed the contribution of LncRNA ZNRD1-AS1 to the development of lung cancer in Asian population.

AXIN2 rs2240308 polymorphism contributes to increased cancer risk: evidence based on a meta-analysis.

BackgroundVariants in the axis inhibition 2 (AXIN2) gene might alter the protein’s structure or function or create a multiprotein destruction complex in the Wnt signaling pathway and thus affect an individual’s susceptibility to cancer. The objective of this study is to evaluate broadly the evidence available for the AXIN2 rs2240308 polymorphism and risk of cancer.MethodsA comprehensive literature search was undertaken for eligible studies in Embase, PubMed, and Cochrane Library up to Nov 30, 2014. Odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs) were used to measure the strength of the models.ResultsEight articles (10 case-control studies with 1,502 cases and 1,590 controls) were included in this analysis. Overall, the AXIN2 rs2240308 polymorphism was associated with a significant increase in the risk of cancer (G allele vs. A allele: OR = 1.21, 95 % CI = 1.05–1.40, I2 = 39.5 % and PQ = 0.094 for heterogeneity; GG vs. AA: OR = 1.30, 95 % CI = 1.04–1.63, I2 = 35.9 % and PQ = 0.121 for heterogeneity; GG vs. GA + AA: OR = 1.36, 95 % CI = 1.17–1.58, I2 = 19.5 % and PQ = 0.263 for heterogeneity). Asian populations showed similar results. Stratified analysis by cancer types indicated that the AXIN2 rs2240308 polymorphism increases the risk of lung cancer (G allele vs. A allele: OR = 1.36, 95 % CI = 1.17–1.59; GA vs. AA: OR = 1.43, 95 % CI = 1.01–2.02; GG vs. AA: OR = 1.93, 95 % CI = 1.36–2.75; GG + GA vs. AA: OR = 1.65, 95 % CI = 1.18–2.30; GG vs. GA + AA: OR = 1.45, 95 % CI = 1.18–1.79. All I2 < 50 % and PQ > 0.100 for heterogeneity).ConclusionsThis study showed that the AXIN2 rs2240308 polymorphism contribute to increasing the risk of cancer, especially lung cancer in Asian populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-015-0219-8) contains supplementary material, which is available to authorized users.

Folate pathway gene MTHFR C677T polymorphism and risk of lung cancer in Asian populations.

Previous studies concerning the association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism with lung cancer in Asian populations have provided inconclusive findings. A meta-analysis was performed to investigate a more reliable association between MTHFR C677T polymorphism and lung cancer in Asians. A comprehensive search was conducted to identify all case-control studies of MTHFR polymorphisms and lung cancer in Asia, using odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of any association. Meta-analysis results suggested that the MTHFR C677T polymorphism contributed to an increased lung cancer risk in Asian populations (for T vs C: OR=1.11, 95%CI=1.0-1.23; for CT vs CC: OR= 1.1, 95%CI= 0.95-1.2 ; for TT+CT vs CC: OR=1.13, 95%CI=1.0-1.30; for TT vs CC: OR=1.25, 95%CI=1.01-1.30; for TT vs CT+CC: OR=1.16, 95%CI=1.0-1.36). MTHFR C677T polymorphism is significantly associated with lung cancer in Asians.

Impact of epoxide hydrolase 1 polymorphisms on lung cancer susceptibility in Asian populations.

Inconsistent association of microsomal epoxide hydrolase (mEH) polymorphisms (Tyr113His, His139Arg) and lung cancer susceptibility have been reported in earlier studies. This study was undertaken to assess if mEH Tyr113His and His139Arg represent risk factors for lung cancer in Asian population. We exhaustively searched multiple databases to identify all eligible studies. Odds ratios were calculated to estimate the strength of genetic associations. This meta-analysis finally combined 2,522 subjects for Tyr113His and 2,725 subjects for His139Arg. In the analysis of Tyr113His, the His/His genotype carriers were found to have 29 % higher risk of lung cancer compared to the Tyr/Tyr carriers (His/His vs. Tyr/Tyr, odds ratio, 1.29, 95 % confidence interval, 1.06-1.58). A significantly increased risk was also seen in His/His versus His/Tyr + Tyr/Tyr (odds ratio, 1.29, 95 % confidence interval, 1.07-1.55). Likewise, His139Arg demonstrated a significant association with lung cancer (Arg/His vs. His/His, odds ratio, 1.2 6, 95 % confidence interval, 1.06-1.49; odds ratio, 1.24, 95 % confidence interval, 1.05-1.46). Stratified analysis by ethnicity showed both of the polymorphisms were associated with lung cancer in Chinese populations. These results suggest that the genetic associations exist between mEH polymorphisms and lung cancer susceptibility in Asian populations.

Genetic association between AGPHD1 variant and lung cancer risk.

The knowledge of molecular mechanism that underlies the genetic predisposition to lung cancer is yet limited. Results from previous studies addressing the association of AGPHD1 variant rs8034191 with lung carcinogenesis remain inconclusive. Herein, we combined these data and re-examined the association. We performed a meta-analysis of Asian studies identified through various ways. Using the data collected from each eligible study, we combined the effect estimates (ORs and its 95 % CIs) with the fixed effects model (Mantel-Haenszel method). Statistical analyses were done using STATA software. Data from nine studies (29,290 subjects) carried out in Asian populations were analyzed in this work. There was no overall association between variant rs8034191 and lung cancer risk under the allele frequency model (OR = 1.03, 95 % CI = 0.93-1.13, P heterogeneity = 0.522). We observed the same associations under other genetic models and in the subgroup analyses by ethnicity and smoking status. Our results indicate that variant rs8034191 in the AGPHD1 gene may not modify the genetic risk of lung cancer in Asian populations.

Association of XPC polymorphisms and lung cancer risk: a meta-analysis.

BackgroundXeroderma pigmentosum complementation group C gene (XPC) is a key member of nucleotide excision repair pathway and plays an important role in human DNA repair system. It is reported that several common polymorphisms of XPC are associated with susceptibility to lung cancer. However, the conclusion is still elusive.MethodThis meta-analysis was performed to determine the relationship between XPC polymorphisms (Lys939Gln, Ala499Val, and PAT) and lung cancer risk. Published literatures were identified by searching online databases and reference lists of relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength. Publication bias were detected by Egger’s and Begg’s test.ResultAfter strict screening, we identified 14 eligible studies in this meta-analysis, including 5647 lung cancer cases and 6908 controls. By pooling all eligible studies, we found that the homozygote Gln939Gln genotype was associated with a significantly increased risk of lung cancer in Asian population (GlnGln vs LysLys, OR = 1.229, 95% CI: 1.000–1.510; GlnGln vs LysLys/LysGln, OR = 1.257, 95% CI: 1.038–1.522). As for the PAT polymorphism, in Caucasian population, we found carriers of the −/− genotype were associated significantly reduced risk of lung cancer in homozygote comparison model (−/− vs +/+, OR = 0.735, 95% CI: 0.567–0.952).ConclusionIn this meta-analysis we found that Gln939Gln genotype was associated with significantly increased risk of lung cancer in Asian population; the PAT −/− genotype significantly reduced susceptibility to lung cancer in Caucasian population; while the XPC Ala499Val polymorphism was not associated with lung cancer risk.

Genetic polymorphism of APE1 rs1130409 can contribute to the risk of lung cancer

Accumulative evidence suggests that polymorphism in the APE1 gene may have association with the etiology of lung cancer by modulating DNA repair capacity. Many studies have evaluated the association with great discrepancies in the results. The present meta-analysis was undertaken to clarify the effects of this polymorphism on lung cancer. A meta-analysis of 15 studies with 4,932 lung cancer patients and 6,555 cancer-free controls was conducted to evaluate the strength of the association using odds ratios (ORs) with 95 % confidence intervals (CIs). Overall, no significant association was found between APE1 polymorphism and lung cancer risk. We also did not observe any statistical evidence of modified lung cancer risk either in smokes or in nonsmokers. In the stratified analysis by ethnicity, however, it was found that the Glu/Clu genotype carriers had 1.16-fold higher risk of suffering lung cancer compared with the carriers of Arg/Glu + Arg/Arg genotypes in Asian population (OR = 1.16, 95 % CI = 1.01-1.32, P = 0.242). This meta-analysis provides statistical evidence for a potential association between APE1 polymorphism and an increased risk of lung cancer in Asian population.

X-ray repair cross-complementing group 1 codon 399 polymorphism and lung cancer risk: an updated meta-analysis

Many epidemiologic studies have investigated the association between x-ray repair cross-complementing group 1 gene (XRCC1) codon 399 polymorphism and lung cancer risk, but the results were inconsistent. We performed a meta-analysis of 46 studies on XRCC1 codon 399 polymorphism and lung cancer risk published before June 2013. In general population, the M allele and MM genotype were associated with increased risk of lung cancer compared with C allele and CC genotype, and the ORs were 1.06 (95% CI 1.01-1.12) and 1.19 (95% CI 1.05-1.34), respectively. When it was stratified according to Asian population, the association between XRCC1 codon 399 polymorphism and lung cancer risk was further strengthened. The ORs of comparison between M vs. C, MM vs. CC, and MM vs. CM + CC were 1.14 (95% CI 1.03-1.26), 1.41 (95% CI 1.11-1.78), and 1.38 (95% CI 1.12-1.71), respectively. The association between codon 399 polymorphism and lung cancer risk in nonsmoking Chinese women was stronger than any other subgroups. However, no associations were found in the Caucasian and African population. This meta-analysis has demonstrated that codon 399 polymorphism of XRCC1 gene might contribute to individual's susceptibility to lung cancer in Asian population, and especially in nonsmoking Chinese women. Future studies focused on interactions between combined genes and environmental risk factors are warranted.

Association between myeloperoxidase G-463A polymorphism and lung cancer risk

Many epidemiologic studies have investigated the association between myeloperoxidase (MPO) G-463A polymorphism and lung cancer risk, but the results were controversial. We performed a meta-analysis of 25 studies on MPO polymorphism and lung cancer risk published before July 2013. The allele of A was found to be associated with decreased risk of lung cancer compared with G allele (OR, 0.90; 95% CI, 0.82-0.98) in the general population. The significant association remained in the comparison between AA + AG and GG (OR, 0.92; 95% CI, 0.87-0.98). When it was stratified according to Asian population, the association between MPO polymorphism and lung cancer risk was further strengthened. However, no associations were found in the Caucasian population. This meta-analysis has demonstrated that MPO polymorphism might contribute to individual's susceptibility to lung cancer in Asian population. Caucasian authors could re-investigate the association between MPO polymorphism and lung cancer risk with more specific participants. Future studies focusing on interactions between combined genes and environmental risk factors are warranted.

GSTT1 Null Genotype Contributes to Lung Cancer Risk in Asian Populations: A Meta-Analysis of 23 Studies

BackgroundGenetic variation in glutathione S-transferases (GSTs) may contribute to lung cancer risk. Many studies have investigated the correlation between the Glutathione S-transferase T1 (GSTT1) null genotype and lung cancer risk in Asian population but yielded inconclusive results.Methodology/Principal FindingsWe performed a meta-analysis of 23 studies including 4065 cases and 5390 controls. We assessed the strength of the association of GSTT1 with lung cancer risk and performed sub-group analyses by source of controls, smoking status, histological types, and sample size. A statistically significant correlation between GSTT1 null genotype and lung cancer in Asian population was observed (OR = 1.28, 95% CI = 1.10, 1.49; Pheterogeneity<0.001 and I2 = 62.0%). Sub-group analysis revealed there was a statistically increased lung cancer risk in ever-smokers who carried the GSTT1 null genotype (OR = 1.94, 95% CI = 1.27, 2.96; P heterogeneity = 0.02 and I2 = 58.1%). It was also indicated that GSTT1 null genotype could increase lung cancer risk among population-based studies (OR = 1.25, 95% CI = 1.04, 1.50; Pheterogeneity = 0.003 and I2 = 56.8%). The positive association was also found in studies of sample size (≤500 participants) (OR = 1.34, 95% CI = 1.10, 1.62; Pheterogeneity<0.001 and I2 = 65.4%).ConclusionsThese meta-analysis results suggest that GSTT1 null genotype is associated with a significantly increased risk of lung cancer in Asian population.