Lung Cancer In Asians Research Articles

Polymorphisms in solute carrier genes (SLC19A1, SLCO1B1, and SLCO1B3) predicts survival and toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.

Solute Carrier (SLC) transporters are known mediators of drug disposition that facilitate the influx of substrates and various chemotherapeutic agents into cells. Polymorphisms in the SLC19A1, SLCO1B1, and SLCO1B3 gene influence the prognosis in the cancer patients, but little is known about their role in lung cancer in Asians. So, the current study aims to investigate the polymorphisms in SLC19A1, SLCO1B1, and SLCO1B3 genes in Northern Indian lung cancer patients. Patients with lung cancer who had a confirmed histology and cytology diagnosis were enrolled in the study. SLC polymorphisms were assessed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) for variations in SLC19A1 (G80 A), SLCO1B1 (A388 G, T521 C), and SLCO1B3 (A1683-5676 G). Our results showed that mutant genotype for SLC19A1 G80 A polymorphism had higher median survival time (MST) compared to wild genotype. ADCC patients with mutant genotype showed better survival compared to wild genotype for SLC19A1 G80 A. SCLC patients G80 A polymorphism showed increased survival in patients with mutant genotype (p=0.04). In SLCO1B3, A1683-5676 G patients carrying heterozygous alleles and administered with platinum and docetaxel showed inferior survival (p=0.006). In T521 C variant, patients with carrier genotype had reduced chances of developing anaemia (p=0.04). Patients with SLC19A1 and SLCO1B3 variants showed lower incidence of thrombocytopenia and nephrotoxicity. Our findings imply that Solute Carrier gene polymorphisms modulate the overall survival in lung cancer patients undergoing platin-based doublet chemotherapy, also these polymorphisms have a modifying impact on the associated adverse events/toxicity.

Development and Validation of a Concise Prediction Scoring System for Asian Lung Cancer Patients with EGFR Mutation Before Treatment.

Purpose We aimed to determine the epidermal growth factor receptor (EGFR) genetic profile of lung cancer in Asians, and develop and validate a non-invasive prediction scoring system for EGFR mutation before treatment. Methods This was a single-center retrospective cohort study using data of patients with lung cancer who underwent EGFR detection (n = 1450) from December 2014 to October 2020. Independent predictors were filtered using univariate and multivariate logistic regression analyses. According to the weight of each factor, a prediction scoring system for EGFR mutation was constructed. The model was internally validated using bootstrapping techniques and temporally validated using prospectively collected data (n = 210) between November 2020 and June 2021.Results In 1450 patients with lung cancer, 723 single mutations and 51 compound mutations were observed in EGFR. Thirty-nine cases had two or more synchronous gene mutations. We developed a scoring system according to the independent clinical predictors and stratified patients into risk groups according to their scores: low-risk (score <4), moderate-risk (score 4-8), and high-risk (score >8) groups. The C-statistics of the scoring system model was 0.754 (95% CI 0.729-0.778). The factors in the validation group were introduced into the prediction model to test the predictive power of the model. The results showed that the C-statistics was 0.710 (95% CI 0.638-0.782). The Hosmer–Lemeshow goodness-of-fit showed that χ2 = 6.733, P = 0.566. Conclusions The scoring system constructed in our study may be a non-invasive tool to initially predict the EGFR mutation status for those who are not available for gene detection in clinical practice.

The cell cycle regulatory gene polymorphisms TP53 (rs1042522) and MDM2 (rs2279744) in lung cancer: a meta-analysis.

Lung cancer is one of the most common types of cancer in the world. Although the mechanism of lung cancer is still unknown, a large number of studies have found a link between gene polymorphisms and the risk of lung cancer. The tumor suppressor p53 plays a crucial role in maintaining genomic stability and tumor prevention. MDM2 is a critical regulator of the p53 protein. Despite the importance of p53 pathway in cancer, data on the contribution of SNPs of TP53 (rs1042522) and MDM2 (rs2279744) to the development of lung cancer are very contradictory. A metaanalysis that collects quantitative data from individual studies and combines their results has the advantage of improving accuracy, providing reliable estimates, and resolving those issues in which studies on individual associations are not effective enough. The aim of this study was to determine whether the TP53 (rs1042522) and MDM2 (rs2279744) polymorphisms confer susceptibility to lung cancer. A meta-analysis was conducted on the associations between the TP53 (rs1042522) and MDM2 (rs2279744) polymorphisms and lung cancer. A total of 51 comparison studies including 25,366 patients and 25,239 controls were considered in this meta-analysis. The meta-analysis showed no association between lung cancer and MDM2 (rs2279744) under any model. A noteworthy association of TP53 (rs1042522) with susceptibility to lung cancer in overall pooled subjects was observed under three different models (allele contrast, homozygote contrast (additive) and dominant). Stratification by ethnicity indicated an association between the TP53 (rs1042522) and lung cancer in Asians and Caucasians. This meta-analysis demonstrates that the TP53 (rs1042522), but not MDM2 (rs2279744) polymorphism may confer susceptibility to lung cancer.

Genomic characteristics in Chinese non-small cell lung cancer patients and its value in prediction of postoperative prognosis.

BackgroundThe genomic profile of non-small cell lung cancer (NSCLC) in Asians is distinct from that of Caucasians, but comprehensive genetic profiling reports have been limited for Asian patients. We aimed to elucidate genomic characteristics of Chinese NSCLC patients and develop potential model including genomic characteristics to predict postoperative prognosis.MethodsResected tumor samples from 511 patients with stage I–IV lung cancer were subjected to targeted sequencing using a panel of 295 cancer-related genes. Based on the molecular profiles and clinical features, we established nomogram models with predictors consisting of integrated clinical and genomic characteristics to provide post-operative risk stratification.ResultsCompared to the TCGA population (mainly Caucasians), there was a significantly higher frequency of EGFR (53.7% vs. 14.4%) and NOTCH3 (8.4% vs. 1.3%) mutations and less mutated KRAS (11.0% vs. 32.6%), KEAP1 (4.4% vs. 17.4%) and LRP1B (16.3% vs. 29.6%) in Chinese lung adenocarcinomas (LUAD). Distinct patterns of mutually exclusive and co-occurring mutations were identified between LUAD and lung squamous cell carcinoma (LUSC), indicating the unique histology-specific tumorigenesis mechanism of each subtype. We observed alterations in pathways correlated with clinical characteristics. Additionally, we constructed nomogram model with predictors consisting of clinical and genomic characteristics, which were more accurate than models with clinical characteristics or TNM staging only both in stage I–IIIA patients and T1-2N0M0 sub-cohort.ConclusionsThis study revealed Chinese NSCLC patients have unique genomic profile. Furthermore, the nomogram model combining clinical features with genomic characteristics could improve risk stratification in early-stage NSCLC.

Association between HIF-1α gene polymorphisms and lung cancer: A meta-analysis.

Hypoxia-inducible factor-1 (HIF-1), an important component of angiogenesis, is activated as a response to tumor hypoxia and facilitates tumor survival. Several case–control articles stressed the connection between lung cancer danger and HIF-1α gene polymorphism, but the conclusions were conflicting. Thus, this meta-analysis was carried out to assess the connection between HIF-1α gene polymorphisms (rs11549467, rs11549465, and rs2057482) and lung cancer risk.PubMed, Embase, Cochrane Library, and Google Scholar were systematically searched up to November 1, 2018. The study quality was quantified by the c. The odds ratios (ORs) and 95% confidence intervals (CIs) were pooled in 5 genetic models for assessment under a fixed- or random-effect model. Subgroup analyses were carried out by ethnicity and genotype method. Sensitivity analysis and publication bias were tested. Five eligible articles were enrolled.The rs11549467 significantly increased the lung cancer risk (OR [95% CI]: A vs G, 1.68 [1.03–2.76]; AA + AG vs GG, 1.70 [1.14–2.54]; AA vs GG, 1.59 [1.21–2.10]), whereas neither rs11549465 nor rs2057482 was related with the lung cancer risk. Subgroup analysis showed rs11549465 and rs11549467 increased lung cancer risk among Asians, but not whites. HIF-1α rs2057482 was unrelated to the risk of lung cancer in Asians and whites.HIF-1α gene rs11549465 and rs11549467, but not rs2057482, increased the risk of lung cancer among Asians.

Certain interleukin polymorphisms might influence predisposition to lung cancer: A meta-analysis of 35 published studies.

Interleukin polymorphisms might influence predisposition to lung cancer (LC), but the results of already published studies regarding the relationship between interleukin polymorphisms and LC were still controversial and ambiguous. So the authors designed this meta-analysis to more precisely estimate relationship between interleukin polymorphisms and LC by pooling the results of already published related studies. The authors searched Pubmed, Embase, Web of Science, and CNKI for already published studies. Thirty-five already published studies were pooled and analyzed in this meta-analysis. The pooled meta-analyses results showed that distributions of IL-4 rs2243250 polymorphism among patients and controls from Asian countries differed significantly (dominant comparison: OR = 1.29, 95% CI 1.07-1.55; overdominant comparison: OR = 0.83, 95% CI 0.73-0.95; allele comparison: OR = 1.26, 95% CI 1.03-1.54), and distributions of IL-10 rs1800872 polymorphism among patients and controls from Caucasian countries also differed significantly (recessive comparison: OR = 0.54, 95% CI 0.35-0.83; overdominant comparison: OR = 1.26, 95% CI 1.05.1.51). No genotypic distribution differences were observed for IL-4 rs2070874, IL-6 rs1800795, IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800871, and IL-10 rs1800896 polymorphisms in pooled meta-analyses. This meta-analysis suggested that IL-4 rs2243250 might influence predisposition to LC in Asians, whereas IL-10 rs1800872 polymorphism might influence predisposition to LC in Caucasians.

Racial disparities in lung cancer incidence and mortality over the last two decades; a Population-Based Study

Abstract Background Racial disparities in the incidence and survival of lung cancer patients have been thoroughly studied. However, large epidemiologic studies evaluating temporal trends based on race are not prevalent. In this study, we aim to evaluate trends of incidence and mortality of lung cancer patients with a focus on patients of Asian origins. Methods We used SEER 18 database to study lung cancer cases in the US during 2000-2015. Incidence and mortality rates of lung cancer were calculated by race and were expressed by 100,000 person-years. Annual percent change (APC) was calculated using joinpoint regression software. All statistical tests were two-sided. Results 794,319 patients with lung cancer were identified. Most patients were whites (83.32%), followed by blacks (10.85%), Asians (5.37%), and American Indians (4.68%), with incidence rates of 60.86, 67.538, 37.325, and 32.195 per 100,000 person-years, respectively. Incidence rates of lung cancer decreased significantly among Asians during the study period, with this decrease being more prominent since 2012 (APC=-3.148%, p-value= 0.018). Similar trends were observed in other races. Mortality due to lung cancer was 49.001, 56.245, 28.916, and 27.980 per 100,000 person-years in whites, blacks, Asians, and American Indians, respectively. Mortality rates of both Asians increased significantly from 2000-2009 (APC=2.429%, P Conclusion Patients of Asian origins have shown lower incidence and mortality rates of lung cancer when compared to whites or blacks. Despite the declining incidence of lung cancer in Asians, mortality was inclining early 2000s yet started to decline since 2013. Understanding the root causes of the earlier incline and later decline can help improve survival in Asian lung cancer patients and lead to a further decline in mortality rates in the near future.

COX-2 rs5275 and rs689466 polymorphism and risk of lung cancer: A PRISMA-compliant meta-analysis.

Background:Cyclooxygenase-2 (COX-2) is an inducible enzyme that mediates the synthesis of prostaglandin, which plays an important role in the inflammation response. The overexpression of COX-2 in lung cancer has been found in several studies, suggesting that COX-2 contributes to carcinogenesis. There are many previous case-control studies focused on the association between COX-2 polymorphism and lung cancer risk, however, the conclusion remained controversial.Objectives:We performed this meta-analysis to evaluate the association between COX-2 rs5275 and rs689466 polymorphism and susceptibility to lung cancer.Methods:A systematic literature research was conducted on PubMed, Embase, Cochrane Library, OVID, Web of Science, and Google Scholar up to November 30, 2017. The quality of studies was assessed by Newcastle–Ottawa scale. We combined odds ratios (ORs) and 95% confidence intervals (CIs) in 5 different genetic models for evaluation under a fixed-effect model or random-effect model. Subgroup analysis was performed according to source of control, ethnicity, pathological types, and smoking status. Sensitivity analysis and publication bias were also conducted.Results:Eventually, 14 eligible studies were included in our meta-analysis. We found rs5275 gene polymorphism decreased the risk of lung cancer under heterozygote model (OR: 0.91, 95% CI: 0.84–0.98, P = .02). COX-2 rs689466 gene polymorphism was also related to a significantly reduced risk under allele (OR: 0.88, 95% CI: 0.82–0.95, P = .001), homozygote (OR: 0.81, 95% CI: 0.68–0.95, P = .01), heterozygote (OR: 0.81, 95% CI: 0.72–0.91, P < .001), and dominant model (OR: 0.81, 95% CI: 0.72–0.91, P < .001), except for recessive model. Subgroup analysis suggested a similar association in Asians, but not in Caucasians. Polymorphism of rs5275 was strongly associated with a reduced risk of lung adenocarcinoma according to stratified analysis by pathological types. Egger test identified no significant publication bias.Conclusions:Our meta-analysis demonstrated that COX-2 rs5275 and rs689466 polymorphism significantly decrease the risk of lung cancer in Asians but not in Caucasians, indicating COX-2 could serve as a potential diagnostic marker for lung cancer.

MicroRNA-200 families and prognostic value in various carcinomas: A systematic review and meta-analysis.

BackgroundRecently, some studies have showed that miR‐200 families act as novel biomarkers for the prediction of cancer outcomes.AimsThis meta‐analysis was designed to investigate the associations between miR‐200 families and the prognosis of patients with various cancers.Materials & MethodsEligible published databases including PubMed, Embase and Chinese National Knowledge Infrastructure (CNKI) databases were searched for articles until October 18, 2016. We performed a meta‐analysis by calculating pooled hazard ratios (HR) and 95% confidence intervals (CI). Data were extracted from studies comparing overall survival (OS), progression‐free survival (PFS) or recurrence‐free survival (RFS).ResultsFor OS, the pooled HR was 1.54 (95% CI: 1.01‐2.33), showing that high miR‐200 family was clearly related to poor survival in various carcinomas, but no significantly association was found in PFS or RFS. Subgroup analysis indicated that upregulated miR‐200 family was linked to poor OS in Asians (HR = 2.19, 95% CI: 1.27‐3.78) but not in Caucasians (HR = 0.94, 95% CI: 0.46‐1.91). Similarly, high miR‐200 expression could not clearly predict the relationship with PFS and RFS. For cancer type, high miR‐200 also predicted poor OS among lung cancer patients (HR = 3.09, 95% CI: 1.75‐5.46). Besides, only elevated miR‐200c of the miR‐200 family indicated a significantly poor OS (HR = 2.25, 95% CI: 1.39‐3.64).DiscussionAberrant expression of miRNAs played a crucial role in the area of human carcinomas. Many studies have indicated that miRNAs are considered promising tumor biomarkers for prognosis and potential targets for clinical treatment. We have testified that high levels of miR‐200 family expression (predominantly miR‐200c) are significantly associated with poor survival and prognostic outcomes of patients with cancers, especially in lung cancer. However, no statistically significant results were calculated for miR‐200a/b and miR‐429, and this might result from a relatively small number of articles about them. In other tumor models except lung cancer, our results indicated that high miR‐200 family was not obviously associated with OS (Gastric or Colorectal cancer; Ovarian cancer; Others). In addition, some other records showed the opposite results, for they exhibited that upregulated miR‐200 family level was linked to longer survival. For ethnic group, our stratified analyses showed that the Asian population predicted poor OS. While the Caucasian population did not exhibit an significant association with OS. This discrepancy might result from different hereditary backgrounds and environment exposure. Although these results have indicated that miR‐200 families were promising biomarkers to predict prognosis for patients with cancers, there were several limitations in this analysis that would impact its quality. Generally, further studies should be warranted to clarify this question and to provide a new novel idea for routine clinical application.ConclusionOur findings suggest that miR‐200 family might be a potentially useful biomarker for predicting cancer prognosis, especially for lung cancer in Asians.

CLPTM1L gene rs402710 (C > T) and rs401681 (C > T) polymorphisms associate with decreased cancer risk: a meta-analysis.

Cleft lip and palate transmembrane 1-like (CLPTM1L) gene rs402710 (C > T) and rs401681 (C > T) polymorphisms have been widely studied for their potential relation to cancer risk, but studies have produced conflicting results. To systematically evaluate the association between these two polymorphisms and overall cancer risk, we conducted a comprehensive meta-analysis on all relevant articles found in the PubMed and EMBASE databases published prior to May 1, 2017. There were 26 articles with 28 studies, including 30,770 cases and 34,089 controls, for the rs402710 polymorphism and 38 articles with 48 studies, including 67,849 cases and 328,226 controls, for the rs401681 polymorphism. The pooled results indicated that both rs402710 and rs401681 polymorphisms are significantly associated with decreased overall cancer risk. In our stratification analysis, a significant association of the rs402710 polymorphism with lung and bladder cancers was identified among Asian and Caucasian populations in both hospital-based and population-based studies. The rs401681 polymorphism was significantly associated with a decreased risk of lung cancer, bladder cancer, and basal cell carcinoma in Asians and in hospital-based studies. CLPTM1L gene rs402710 and rs401681 polymorphisms thus have a protective association with various types of cancer, especially lung cancer among Asians.

Association between 8q24 rs6983267 polymorphism and cancer susceptibility: a meta-analysis involving 170,737 subjects.

Published data on the association between 8q24 rs6983267 polymorphism and cancer risk are inconsistent. Thus, we conducted a meta-analysis to evaluate the relationship between rs6983267 polymorphism and cancer risk. We searched on PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) up to November 1, 2016 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of this association. We included 78 case-control studies with a total of 73,996 cases and 96,741 controls in this meta-analysis. The pooled results showed that rs6983267 polymorphism was significantly associated with increased risk of overall cancer in all genetic models (dominant model: OR = 1.19, 95% CI = 1.13–1.26; recessive model: OR = 1.19, 95% CI = 1.14–1.25; homozygous model: OR= 1.31, 95% CI = 1.23–1.40; heterozygous model: OR = 1.14, 95% CI = 1.10–1.19; allelic model: OR = 1.14, 95% CI = 1.11–1.18). Stratified analyses indicated that rs6983267 significantly increased the risk of colorectal cancer in Caucasians, prostate cancer in Caucasians and Asians, thyroid cancer in Caucasians and lung cancer in Asians. When studies were stratified by study quality, source of controls and genotyping method, significant associations were especially found in the high quality studies, the publication-based studies, the hospital-based studies, and the PCR-RFLP studies. Additional well-designed studies with large samples should be performed to validate our results.

The association between proton pump inhibitors (PPI) use for gastro-esophageal reflux disease (GERD) and lung cancer (LC): A nested case-control study.

1562 Background: Data suggests that GERD with recurrent reflux and microaspiration of stomach contents, may be associated with lung injury, inflammation, activation of proliferative signals, and eventually DNA damage and malignant transformation. Recently, a large population based cohort study found that GERD may increase the risk of lung cancer in Asians. In the present nested case control study, we aimed to evaluate the association between PPI use as a surrogate for GERD and lung cancer in a large western population. Methods: We conducted a matched case-control study within a population-representative database from the United Kingdom. Study cases were defined as individuals with any diagnostic code of lung cancer. For every case, four eligible controls were matched on age, gender, practice site, time and duration of follow-up. Exposure of interest was PPI use prior to cancer diagnosis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer were estimated using conditional logistic regression. Adjustment was performed for smoking. Results: The study population included 19143 lung cancer cases and 74473 matched controls. PPI use was associated with a significantly increased lung cancer risk (adjusted OR 1.70, 95%CI 1.64-1.77, p &lt; 0.001). In a sensitivity analyses we observed similar associations when PPI use was initiated more than one year prior to cancer diagnosis (adjusted OR 1.18, 95%CI 1.13-1.23, p &lt; 0.001) and more than two years prior to cancer diagnosis (adjusted OR 1.15, 95%CI 1.10-1.20, p &lt; 0.001) Conclusions: ChronicPPI use, as a surrogate for symptomatic GERD, may be associated with a higher lung cancer risk.

EGFR-TKI Versus Chemotherapy for Previously Untreated Advanced Non-Small Cell Lung Cancer in Asians: A Meta-Analysis

EGFR-TKI Versus Chemotherapy for Previously Untreated Advanced Non-Small Cell Lung Cancer in Asians: A Meta-Analysis

Risk of lung cancer in patients with gastro-esophageal reflux disease: a population-based cohort study.

This large-scale, controlled cohort study estimated the risks of lung cancer in patients with gastro-esophageal reflux disease (GERD) in Taiwan. We conducted this population-based study using data from the National Health Insurance Research Database of Taiwan during the period from 1997 to 2010. Patients with GERD were diagnosed using endoscopy, and controls were matched to patients with GERD at a ratio of 1:4. We identified 15,412 patients with GERD and 60,957 controls. Compared with the controls, the patients with GERD had higher rates of osteoporosis, diabetes mellitus, asthma, chronic obstructive pulmonary disease, pneumonia, bronchiectasis, depression, anxiety, hypertension, dyslipidemia, chronic liver disease, congestive heart failure, atrial fibrillation, stroke, chronic kidney disease, and coronary artery disease (all P < .05). A total of 85 patients had lung cancer among patients with GERD during the follow-up of 42,555 person-years, and the rate of lung cancer was 0.0020 per person-year. By contrast, 232 patients had lung cancer among patients without GERD during the follow-up of 175,319 person-years, and the rate of lung cancer was 0.0013 per person-year. By using stepwise Cox regression model, the overall incidence of lung cancer remained significantly higher in the patients with GERD than in the controls (hazard ratio, 1.53; 95% CI [1.19–1.98]). The cumulative incidence of lung cancer was higher in the patients with GERD than in the controls (P = .0012). In conclusion, our large population-based cohort study provides evidence that GERD may increase the risk of lung cancer in Asians.

Meta-Analysis of First-Line Pemetrexed Plus Platinum Treatment in Compared to Other Platinum-Based Doublet Regimens in Elderly East Asian Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer

BackgroundPemetrexed plus platinum has become a standard of care in first-line treatment for patients with advanced nonsquamous non–small-cell lung cancer. However, elderly lung cancer patients are generally understudied and undertreated in clinical practice in East Asia because of safety concerns. This analysis aimed to provide a picture of the clinical benefit of pemetrexed/platinum in the first-line setting for elderly (age ≥ 65 years) East Asian patients. Patients and MethodsIndividual patient data from 3 randomized controlled phase 3 trials that enrolled East Asian patients were analyzed in this meta-analysis. ResultsIn elderly East Asian patients (63 in the pemetrexed/platinum group and 42 in the control group), pemetrexed/platinum treatment achieved more benefits compared to other platinum-based doublets, including better overall response rate (32.8% vs. 7.5%), favorable progression-free survival (not statistically significant in adjusted hazard ratio), and significantly longer (3.15 vs. 1.54 months) survival without drug-related grade 3/4 toxicity. Overall survival was numerically prolonged (16.33 vs. 13.77 months; not statistically significant). These benefit trends were similar to those in all-age East Asian patients. In elderly East Asians, pemetrexed/platinum treatment was also associated with a lower incidence rate of drug-related grade 3/4 adverse events. The adverse event profile was similar to that in all-age East Asians. There were no unexpected adverse events. ConclusionPemetrexed/platinum had good efficacy and also resulted in better overall response and tolerability than other platinum-based doublets as first-line treatment in nonsquamous non–small cell lung cancer in elderly East Asians, which was consistent with data observed in all-age East Asians.

Survivin protein expression is involved in the progression of non-small cell lung cancer in Asians: a meta-analysis.

BackgroundSurviving expression might serve as a prognostic biomarker predicting the clinical outcome of non-small cell lung cancer (NSCLC). The study was conducted to explore the potential correlation of survivin protein expression with NSCLC and its clinicopathologic characteristics.MethodsPubMed, Medline, Cochrane Library, CNKI and Wanfang database were searched through January 2016 with a set of inclusion and exclusion criteria. Data was extracted from these articles and all statistical analysis was conducted by using Stata 12.0.ResultsA total of 28 literatures (14 studies in Chinese and 14 studies in English) were enrolled in this meta-analysis, including 3206 NSCLC patients and 816 normal controls. The result of meta-analysis demonstrated a significant difference of survivin positive expression between NSCLC patients and normal controls (RR = 7.16, 95 % CI = 4.63-11.07, P < 0.001). To investigate the relationship of survivin expression and clinicopathologic characteristics, we performed a meta-analysis in NSCLC patients. Our results indicates survivin expression was associated with histological differentiation, tumor-node-metastasis (TNM) stage and lymph node metastasis (LNM) (RR = 0.80, 95 % CI = 0.73-0.87, P < 0.001; RR = 0.75, 95 % CI = 0.67-0.84, P < 0.001; RR = 1.14, 95 % CI = 1.01-1.29, P = 0.035, respectively), but not pathological type and tumor size. (RR = 1.00, 95 % CI = 0.93-1.07, P = 0.983; RR = 0.95, 95 % CI = 0.86-1.05, P = 0.336, respectively).ConclusionHigher expression of survivin in NSCLC patients was found when compared to normal controls. Survivin expression was associated with the clinicopathologic characteristics of NSCLC and may serves as an important biomarker for NSCLC progression.

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.

Association Between Interleukin-8 –251A/T Polymorphism and Risk of Lung Cancer: A Meta-Analysis

This study is to evaluate the association between IL-8 –251A/T polymorphism and lung cancer risk in diverse populations. We performed a meta-analysis of six case-control studies that included 3,265 lung-cancer cases and 3,607 case-free controls. Overall, results showed that the IL-8 –251A/T polymorphism was not associated with a significantly increased risk of lung cancer in all genetic models. However, stratified by ethnicity, a significantly increased risk was found among Asians. In conclusion, IL-8 –251A/T polymorphism is associated with lung cancer susceptibility in Asians and the –251 A allele may increase risk of lung cancer in Asians.

Association between TNF-α gene 308G>A polymorphism and lung cancer risk: a meta-analysis.

Many studies have investigated the association between tumor necrosis factor alpha (TNF-α) gene 308G/A polymorphism and lung cancer risk, but the results were inconsistent. We thus comprehensively searched the PubMed, EMBASE, and BIOSIS Previews databases and extracted data from all eligible articles to estimate the association between TNF-α gene 308G/A polymorphism and lung cancer risk. The pooled odds ratio (OR) with 95 % confidence intervals (CIs) were calculated. Twelve case-control studies in 11 articles involving 2,436 cases and 2,573 controls were included in the meta-analysis to assess the association between TNF-α gene 308G>A polymorphism and susceptibility to lung cancer. Overall, TNF-α gene 308G>A polymorphism was significantly associated with an increased risk of lung cancer for A vs. G (OR = 1.13, 95 % CI 1.00 ~ 1.27, P = 0.04). Subgroup analysis by ethnicity showed that there was a significant association between TNF-α gene 308G>A polymorphism and increased risk of lung cancer in Asians, but not in Caucasians. In subgroup analysis by tumor type, there were significant associations between TNF-α gene 308G>A polymorphism and increased risk of lung cancer in small cell lung cancer (SCLC) for AA+AG vs. GG, in non-small cell lung cancer (NSCLC) for A vs. G, AA vs. GG, and AA+AG vs. GG. No association between the genotypes and different stages of lung cancer was detected. The meta-analysis suggests that TNF-α gene 308G>A polymorphism is associated with an increased risk of lung cancer, particularly among Asians, both for SCLC and NSCLC, considering tumor type.

Associations between 25 Lung Cancer Risk–Related SNPs and Polycyclic Aromatic Hydrocarbon–Induced Genetic Damage in Coke Oven Workers

Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNP) associated with lung cancer. However, whether these SNPs are associated with genetic damage, a crucial event in cancer initiation and evolution, is still unknown. We aimed to establish associations between these SNPs and genetic damage caused by the ubiquitous carcinogens, polycyclic aromatic hydrocarbons (PAH). We cross-sectionally investigated the associations between SNPs from published GWAS for lung cancer in Asians and PAH-induced genetic damage in 1,557 coke oven workers in China. Urinary PAH metabolites, plasma benzo[a]pyrene-r-7,t-8,c-10-tetrahydrotetrol-albumin (BPDE-Alb) adducts, urinary 8-hydroxydeoxyguanosine (8-OHdG), and micronuclei (MN) frequency were determined by gas chromatography-mass spectrometry, sandwich ELISA, high-performance liquid chromatography, and cytokinesis-block micronucleus assay, respectively. 13q12.12-rs753955C was suggestively associated with elevated 8-OHdG levels (P = 0.003). Higher 8-OHdG levels were observed in individuals with rare allele homozygotes (CC) than in TT homozygotes (β, 0.297; 95% confidence interval, 0.124-0.471; P = 0.001). 9p21-rs1333040C, 10p14-rs1663689G, and 15q25.1-rs3813572G were significantly associated with lower MN frequency (P values were 0.002, 0.001, and 0.005, respectively). 10p14-rs1663689G polymorphism downregulated the relationship of the total concentration of PAH metabolites to 8-OHdG levels (Pinteraction = 0.002). TERT-rs2736100G and VTI1A-rs7086803A aggravated the relationship of BPDE-Alb adducts to MN frequency, whereas BPTF-rs7216064G attenuated that correlation (all Pinteraction < 0.001). Lung cancer risk-associated SNPs and their correlations with PAH exposure were associated with 8-OHdG levels and MN frequency. Lung cancer risk-associated SNPs might influence one's susceptibility to genetic damage caused by PAHs. Cancer Epidemiol Biomarkers Prev; 23(6); 986-96. ©2014 AACR.