Association between blood heavy metals and lung cancer risk: A case-control study in China.

BACKGROUND: Exposure to various metals has been reported to lead to lung cancer. However, few studies focused on the combined effects of metal mixture. OBJECTIVE: To explore the relationship between metal mixture and lung cancer patients. METHODS: Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of 8 heavy metals (V, Cr, Mn, Se, Mo, Cd, Ba and Pb) in serum samples of 86 cases and 105 controls in the Tianjin Lung Cancer Cohort. Logistic regression models were used to estimate the effect of each metal on the risk of lung cancer. The restricted cubic spline function was applied to describe the dose-response relationship between various metal concentrations and lung cancer risk. Bayesian Kernel Machine Regression (BKMR), Weighted Quantile Sum (WQS) and Quantile G-Computation (QGC) were employed to explore the effects of metal mixtures as a whole on lung cancer. RESULTS: An increased risk of lung cancer was associated with higher blood Mo concentration (adjusted OR = 2.94, 95% CI = 1.03-8.74 for tertile 2 vs. tertile 1). Higher Se concentration in blood may have protective effects on the risk of lung cancer (adjusted OR = 0.18, 95% CI = 0.06-0.51 for tertile 3 vs. tertile 1, p-trend <0.001). In addition, Se and Cd may have an antagonism effect on the occurrence of lung cancer (RERI and 95% CI = -0.95 [-31.77, -0.07]; AP and 95% CI = -0.95 [-5.16 -0.74]). Although the metal mixture did not show a significant effect on lung cancer as a whole, this may be due to the offsetting effect between positive and negative effects. CONCLUSIONS: Our research indicates that Se has a promising anti-cancer application, but it is necessary to prevent the role of Cd that antagonize Se in lung cancer.

Association between use of antihypertensive drugs and the risk of cancer: a population-based cohort study in Shanghai.

BACKGROUND: Previously studies shown a potential risk of antihypertensive medicines in relation to cancer susceptibility, which creating significant debate in the scientific community and public concern. We sought to investigate the relationship between antihypertensive medicines and cancer risk, by drug type and class. METHODS: We conducted a population-based cohort study and enrolled patients diagnosed with hypertension from community healthcare centers in Changning District, Shanghai, China. Antihypertensive drug administration were classified as five common antihypertensive drugs. The main outcomes were incidence of total cancer and by major cancer type. RESULTS: Between January 2013 and December 2017, a total of 101,370 hypertensive patients were enrolled in this cohort. During a mean follow-up of 5.1 (SD 1.3) years, 4970 cancer cases were newly diagnosed in the cohort. CCBs were the most frequently used antihypertensives which were associated with a moderately increased risk of total cancer (hazard ratio, HR = 1.11, 95% CI: 1.05-1.18). The second commonly used drug ARBs were also associated with increased risk of total cancer (HR = 1.10, 95%CI: 1.03-1.17) as well as lung and thyroid cancers (HR = 1.21, 95%CI: 1.05-1.39; HR = 1.62 95%CI: 1.18-2.21, respectively). No significant association was found between cancer and other antihypertensives. Hypertensive patients who use more than one class of antihypertensives drugs had a higher risk of total cancer (HR: 1.22, 95%CI: 1.10-1.35 for two classes; HR: 1.22, 95%CI: 1.03-1.45 for three or more classes), and a possible dose-response relationship was suggested (P for trend < 0.001). The risk of thyroid cancer was higher in hypertensive patients prescribed with three or more antihypertensive classes. CONCLUSIONS: Use of ARBs or CCBs may be associated with an increased risk of total cancer. Taking more than one class of antihypertensives drugs appeared to have a higher risk for total cancer.

D-Limonene inhibits the occurrence and progression of LUAD through suppressing lipid droplet accumulation induced by PM2.5 exposure in vivo and in vitro.

BACKGROUND: PM2.5 exposure is associated with lung adenocarcinoma (LUAD), but the mechanism is unclear. The lack of understanding impedes our effort on prevention. This study examined a possible mechanism of lung cancer caused by PM2.5 exposure, and aimed to find a potential intervention for people living in PM2.5 polluted regions. METHODS: Electron microscopy and oil-red staining were conducted to examine the lipid droplet accumulation. Masson's trichrome staining, colony forming, scratch assay and transwell experiment were conducted to evaluate the effect of PM2.5 exposure and D-limonene intervention on the occurrence and progression of LUAD. Potential intervention targets were found by RNA-Seq and verified by luciferase reporter assay. MiR-195 KO mice constructed with CRISPR/Cas9 technology were used to investigate the pivotal role of D-limonene-miR-195-SREBP1/FASN axis. Cohort analysis of lung cancer patients, human LUAD tissues staining and human intervention trial were also conducted to validate the results of cell and animal experiments. RESULTS: Our results showed that PM2.5 exposure induced accumulation of lipid droplets in LUAD cells which accompanied by increased malignant cellular behaviors. PM2.5 exposure led to cleaved N-SREBP1 translocation into nucleus, which activated the de novo lipogenesis pathway. Same changes were also observed in normal lung epithelial cells and normal lung tissue, and mice developed pulmonary fibrosis after long-term exposure to PM2.5. Furthermore, in a cohort of 11,712 lung cancer patients, significant lipid metabolism disorders were observed in higher PM2.5 polluted areas. In view of that, D-limonene was found to inhibit the changes in lipid metabolism through upregulating the expression of miR-195, which inhibited the expression of lipogenic genes (SREBF1/FASN/ACACA) specifically. And a small human intervention trial showed that serum miR-195 was upregulated after oral intake of D-limonene. CONCLUSION: Our findings reveal a new mechanism of pulmonary fibrosis and LUAD that is related to PM2.5 exposure-induced lipid droplet accumulation. We also demonstrate that D-limonene-miR-195-SREBP1/FASN axis is a potential preventive intervention for mediating the progression and development of LUAD induced by PM2.5 exposure. Trial registration Chinese Clinical Trial Registry, ChiCTR2000030200. Registered 25 February 2020, http://www.chictr.org.cn/showproj.aspx?proj=48013.

A Novel Signature of Lipid Metabolism-Related Gene Predicts Prognosis and Response to Immunotherapy in Lung Adenocarcinoma.

Background: Lipid metabolism disorder, a new hallmark of cancer initiation, has been involved in lung adenocarcinoma (LUAD). However, few biomarkers about lipid metabolism-related genes (LMRGs) have been developed for prognosis prediction and clinical treatment of LUAD patients. Methods: In this study, we constructed and validated an effective prognostic prediction model for LUAD patients depending on LMRGs. Subsequently, we investigated the prediction model from immune microenvironment, genomic changes, and immunotherapy. Results: Then, eleven LMRGs were identified and applied to LUAD subtyping. In comparison with the high-risk group, the low-risk group exhibited a remarkably favorable prognosis, along with a higher immune score and lower tumor purity. Moreover, the low-risk group presented higher levels of immune checkpoint molecules, lower tumor immune dysfunction and exclusion (TIDE) score and tumor mutation burden (TMB), and higher likelihood of benefiting from immunotherapy. Furthermore, the genomic changes of six LMRGs (CD79A, HACD1, CYP17A1, SLCO1B3, ANGPTL4, and LDHA) were responsible for the difference in susceptibility to LUAD by greatly influencing B-cell activation. Conclusion: Generally speaking, the LMRG model is a reliable independent biomarker for predicting adverse outcomes in LUAD patients and has the potential to facilitate risk-stratified immunotherapy.

Intermittent vs. continuous vancomycin infusion for gram-positive infections: A systematic review and meta-analysis.

OBJECTIVE: The clinical use of intermittent infusion of vancomycin (IIV) and continuous infusion of vancomycin (CIV) is controversial. The aim of this study was to assess the effectiveness and safety of IIV and CIV by using a meta-analysis for cohort studies and randomized controlled trials. METHODS: We compared the probabilities of target attainment (PTA) for the measured concentration (Cm) ≥the target concentration (Ct), the PTA for the area under the drug concentration curve/minimal inhibitory concentration (AUC/MIC) ≥400, the duration of treatment, nephrotoxicity, and overall mortality after vancomycin treatment as reported in PubMed, Embase, Cochrane, and Web of Science. RESULTS: A total of 14 studies with 1640 patients were included in the meta-analysis. For IIV, the PTA of Cm≥Ct (RR=0.72, 95% CI=0.60-0.88), and nephrotoxicity (RR=1.70, 95% CI=1.34-2.14) were significantly different from those of CIV. The treatment duration (SMD=0.08, 95% CI=-0.08-0.25), the PTA of AUC/MIC ≥ 400 (RR=0.84, 95% CI=0.70-1.00) and mortality (RR=0.94, 95% CI=0.72-1.25) were not significantly different from those of CIV. CONCLUSIONS: The results showed that CIV was easier to achieve Ct and safer than IIV. Additional randomized controlled trials focusing on the concentration of vancomycin are needed for further analysis.

A Case/Control Study: AGBL1 Polymorphism Related to Lung Cancer Risk in Chinese Nonsmoking Females.

ATP/GTP binding protein like 1 (AGBL1) plays a role in controlling the length of polyglutamate side chains. Polymorphism rs4513061 in AGBL1 is suspected to influence the risk of lung cancer. A case/control study was performed involving 556 cases and 563 controls from a hospital participating in donation. The relationship between rs4513061 and the risk of lung cancer and the interaction between rs4513061 and environmental exposure were determined by the chi-square tests, logistic regression analysis, and crossover analysis. The survival analysis was conducted by Cox proportional hazard regression. The results showed that rs4513061 polymorphism is associated with the risk of lung cancer. The stratified analysis suggested the protective effect of rs4513061 to different histological types of lung cancer, including lung adenocarcinoma (AA vs. GG: odds ratio [OR] = 0.505, 95% confidence interval [CI] = 0.337-0.756, p < 0.001), squamous cell lung cancer (AG vs. GG: OR = 0.488, 95% CI = 0.269-0.883, p = 0.018), and small-cell lung cancer (AA vs. GG: OR = 0.421, 95% CI = 0.216-0.819, p = 0.011). Nevertheless, there was no significant interaction between rs4513061 and cooking oil fume. Significant impact was not observed between the rs4513061 polymorphism and survival time of lung cancer. Our study indicated that rs4513061 in AGBL1 decreases the risk of lung cancer in nonsmoking females from northeast China.

Association Between Three Polymorphisms in BMAL1 Genes and Risk of Lung Cancer in a Northeast Chinese Population.

The connection between cancer and circadian rhythms has garnered recent attention. BMAL1 is a core factor in the regulation of circadian rhythms, and its variants have frequently been associated with human diseases, including cancer. Our study first clarifies the relationship of three single-nucleotide polymorphisms (rs3816360, rs2290035, and rs3816358) in BMAL1 with the risk of lung cancer, as well as the gene-environment interaction between the polymorphisms and tobacco exposure in a Northeast Chinese population. A case-control study of 409 new diagnosis patients and 417 controls was performed in Shenyang, Liaoning province. The gene-environment interactions were explored on both additive and multiplicative scale. After Bonferroni correction, rs3816360 and rs2290035 were evidently associated with lung cancer risk. For rs3816360, subjects carrying CC (adjusted odds ratio [OR] = 2.163, 95% confidence interval [CI] = 1.413-3.310, p = 0.004) genotype showed an increased risk of lung cancer compared to the subjects carrying homozygous TT genotype. As for rs2290035, homozygous carriers of AA genotype (OR = 1.908, 95% CI = 1.207-3.017, p = 0.006) showed a significantly increased risk of lung cancer. The dominant models and recessive models of rs3816360 and rs2290035 showed significant associations (p < 0.01). In the stratified analysis, our results revealed that rs3816360 and rs2290035 were associated with the risk of lung adenocarcinoma. However, rs3816358 polymorphism was not significantly associated with lung cancer risk. The measures of additive interaction and logistic models suggested that the gene-environment interactions were not statistically significant on both additive and multiplicative scales.

MiR-92a Family: A Novel Diagnostic Biomarker and Potential Therapeutic Target in Human Cancers.

Purpose: This study tried to explore whether members of miR-92a family contribute to early diagnosis and prognosis for human cancers and how they work. Methods: Integrated meta-analysis retrieved from public repositories was employed to assess the clinical roles of the miR-92a family for cancer diagnosis and prognosis. Expression level of miR-92a was detected by the TCGA database and was confirmed by non-small-cell lung cancer (NSCLC) tissues. Targets of miR-92a were predicted using starbase, and validated by dual luciferase assay. Correlation between miR-92a and the target gene was assessed by linkedOmics while expression of the target gene and its role in cancer prognosis were analyzed with UALCAN and Gepia. Results: We recognized the miR-92a family could serve as a potential diagnostic biomarker with a pooled sensitivity of 0.85 [0.81-0.88] and specificity of 0.86 [0.83-0.90]. The overall hazard ratio (HR) was 2.26 [95% CI: 1.70-3.00] for high expression groups compared to low expression groups. Expression of miR-92a was identified to be upregulated in NSCLC, especially in lung squamous cell carcinoma (LUSC). Results from starbase and dual luciferase assay indicated the regulator of G-protein signaling 3 (RGS3) was a direct target of miR-92a. Statistical negative correlation was found for the expression of miR-92a and RGS3. In addition, expression of RGS3 was downregulated in NSCLC and patients with the high expression had a poor prognosis (HR = 1.3) for LUSC patients. However, results were to the contrary for lung adenocarcinoma (HR = 0.7). Conclusion: This study revealed that miR-92a family could be ideal biomarkers for cancer diagnosis and prognosis, which might function through targeting RGS3.

Association Between Two Polymorphisms in the Promoter Region of miR-143/miR-145 and the Susceptibility of Lung Cancer in Northeast Chinese Nonsmoking Females.

Lung cancer is known to cause high mortality and morbidity. The study aimed to explore the association between rs3733845 and rs3733846 polymorphisms in the promoter region of miR-143/145 and the risk of lung cancer among 575 nonsmoking cases and 575 cancer-free controls in a Chinese female population. We genotyped two single nucleotide polymorphisms (SNPs) in the promoter region of miR-143/145 in 575 cases and 575 controls using TaqMan allelic discrimination method. Logistic regression analysis was conducted to assess the association between polymorphisms in the promoter of miR-143/miR-145 and risk of lung cancer females. Crossover analysis was used to explore the interaction between the two SNPs and environmental risk factors (cooking oil fume exposure and passive smoking exposure). The results showed that both rs3733845 and rs3733846 polymorphisms were associated with an increased lung adenocarcinoma risk in dominant model (adjusted odds ratio [OR] = 1.329, 95% confidence intervals [CIs] = 1.026-1.723, p = 0.031 and adjusted OR = 1.450, 95% CI = 1.112-1.890, p = 0.006, respectively). The results of crossover analysis revealed that rs3733845 and rs3733846 risk genotypes along with cooking oil exposure increased lung cancer risk by 1.862-fold and 2.260-fold, respectively (adjusted OR = 1.862, 95% CI = 1.105-3.138, p = 0.020 for rs3733845; adjusted OR = 2.260, 95% CI = 1.354-3.769, p = 0.002 for rs3733846). There was positive multiplicative interaction between the two SNPs and cooking oil fume exposure (adjusted OR = 1.362, 95% CI = 1.078-1.719, p = 0.009 for oil × rs3733845; adjusted OR = 1.399, 95% CI = 1.122-1.745, p = 0.003 for oil × rs3733846). In nonsmoking females, rs3733845 and rs3733846 polymorphisms might be associated with lung adenocarcinoma risk. Moreover, the interactions between the two SNPs and cooking oil fume exposure were statistically significant on a multiplicative scale rather than an addictive scale.

p53/miR-30a-5p/ SOX4 feedback loop mediates cellular proliferation, apoptosis, and migration of non-small-cell lung cancer.

Many microRNAs (miRNAs) play vital roles in the tumorigenesis and development of cancers. In this study, we aimed to identify the differentially expressed miRNAs and their specific mechanisms in non-small-cell lung cancer (NSCLC). Based on data from the GSE56036 database, miR-30a-5p expression was identified to be downregulated in NSCLC. Further investigations showed that overexpression of miR-30a-5p inhibited cell proliferation, migration, and promoted apoptosis in NSCLC. Increase of miR-30a-5p level could induce the increase of Bax protein level and decrease of Bcl-2 protein level. In addition, chromatin immunoprecipitation assays showed that miR-30a-5p expression was induced by binding of p53 to the promoter of MIR30A. Bioinformatics prediction indicated that miR-30a-5p targets SOX4, and western blot analysis indicated that overexpression of the miRNA decreases the SOX4 protein expression level, which in turn regulated the level of p53. Thus, this study provides evidence for the existence of a p53/miR-30a-5p/SOX4 feedback loop, which likely plays a key role in the regulation of proliferation, apoptosis, and migration in NSCLC, highlighting a new therapeutic target.

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.

Clinically Correlated MicroRNAs in the Diagnosis of Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

(1) Background. Non-small cell lung cancer (NSCLC) has a high mortality rate. MiRNAs have been found to be diagnostic biomarkers for NSCLC. However, controversial results exist. We conducted this meta-analysis to evaluate the diagnostic value of miRNAs for NSCLC. (2) Methods. Databases and reference lists were searched. Pooled sensitivity (SEN), specificity (SPE), and area under the curve (AUC) were applied to examine the general diagnostic efficacy, and subgroup analysis was also performed. (3) Results. Pooled SEN, SPE, and AUC were 85%, 88%, and 0.93, respectively, for 71 studies. Multiple miRNAs (AUC: 0.96) obtained higher diagnostic value than single miRNA (AUC: 0.86), and the same result was found for Caucasian population (AUC: 0.97) when compared with Asian (AUC: 0.91) and Caucasian/African population (AUC: 0.92). MiRNA had higher diagnostic efficacy when participants contained both smokers and nonsmokers (AUC is 0.95 for imbalanced group and 0.91 for balanced group) than when containing only smokers (AUC: 0.90). Meanwhile, AUC was 0.91 for both miR-21 and miR-210. (4) Conclusions. Multiple miRNAs such as miR-21 and miR-210 could be used as diagnostic tools for NSCLC, especially for the Caucasian and nonsmoking NSCLC.

Single Nucleotide Polymorphisms in HMGB1 Correlate with Lung Cancer Risk in the Northeast Chinese Han Population.

Lung cancer is the principal cause of cancer-associated deaths. HMGB1 has been reported to be associated with tumorigenesis. This study aimed to investigate the relationship between rs1412125 and rs1360485 polymorphisms in HMGB1 and the risk and survival of lung cancer. 850 cases and 733 controls were included. Logistic regression analysis and survival analysis were performed to investigate the association between SNPs and the risk and survival of lung cancer. Crossover analysis was used to analyze the interaction between SNPs and tobacco exposure. Results indicated that rs1412125 polymorphism was associated with lung cancer risk, especially with the risk of lung adenocarcinoma and small cell lung cancer. Carriers with CT and CC genotypes had a decreased risk of lung cancer (CT + CC vs.TT: adjusted OR = 0.736, p = 0.004). Similar results were obtained in the stratification analysis for non-smokers and female population. For rs1360485 polymorphism, AG and GG genotypes could decrease the risk of lung adenocarcinoma and female lung cancer by 0.771-fold and 0.789-fold. However, no significant interaction between polymorphisms and tobacco exposure or association between SNPs and the survival of lung cancer was observed. This study indicated polymorphisms in HMGB1 may be a novel biomarker for female lung adenocarcinoma risk.

CHL1 gene polymorphisms increase lung cancer susceptibility.

Lung cancer represents a complex and malignant cancer. Close Homologue of L1 (CHL1) gene plays a crucial role in the progress of cancer. The aim of this study is to explore the association between CHL1 rs425366 polymorphism and lung cancer susceptibility in northeast of China. A hospital-based case-control study was carried out to collect relative characteristics. Logistic regression analysis was conducted to analyze the relationship between single nucleotide polymorphisms and lung cancer susceptibility. The results suggested that there was statistically significant difference between GT genotype and TT genotype of rs425366 and lung cancer susceptibility. In stratified analysis, TT genotype of rs425366 may increase the risk of lung adenocarcinoma. We also found that non-smoking individuals carrying T allele were more likely to develop lung cancer. Overall, our study may indicate that CHL1 gene may increase lung cancer susceptibility in northeast of China.

MiR-486 as an effective biomarker in cancer diagnosis and prognosis: a systematic review and meta-analysis.

PURPOSE: MiR-486 was found to be associated with cancer's diagnosis and prognosis. This meta-analysis aimed to investigate the potential effect of miR-486 on cancer detection and prognosis. MATERIALS AND METHODS: We searched PubMed, Cochrane library, Embase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases to find all correlated articles. The STATA 11.0 was applied to estimate the pooled effects, heterogeneity and publication bias. RESULTS: The pooled sensitivity (SEN), specificity (SPE) and Area under the curve (AUC) were 82% (95% CI: 78-85%), 88% (95% CI: 83-92%) and 0.91 (95% CI: 0.88-0.93). Subgroup analysis indicated miR-486 from circulating samples exhibited higher diagnostic accuracy with the AUC was 0.90 (95% CI: 0.87-0.92) than miR-486 from other specimen with the AUC of 0.78 (95% CI: 0.75-0.82) and miR-486 obtained a better diagnostic value in the Asian population with the AUC of 0.94 (95% CI: 0.91-0.95) than the Caucasian and Caucasian/African population with the AUC of 0.80 (95% CI: 0.76-0.83) and 0.89 (95% CI: 0.86-0.91) respectively. MiR-486 obtained high value for the diagnosis of non-small cell lung cancer with SEN, SPE and AUC were 0.82 (95% CI: 0.0.77-0.87), 0.90 (95% CI: 0.84-0.94) as well as 0.92 (95% CI: 0.89-0.94) respectively. For the 7 prognostic tests, the pooled hazard ratio (HR) was 0.48 (95% CI: -0.13-1.08) for low versus high miR-486 expression. CONCLUSIONS: This meta-analysis indicated that miR-486 can be used as ideal biomarkers in the cancer's diagnosis. However, Low miR-486 expression did not increase the risk of poor outcome.

Polymorphisms of rs1347093 and rs1397529 are associated with lung cancer risk in northeast Chinese population.

Lung cancer is one of the malignant tumors with the highest morbidity and mortality all over the world. Here we researched the association between two SNPs (rs1347093 in MIR217HG and rs1397529 in Gab1) and the risk of lung cancer in northeast Chinese population, including 825 cases and 766 controls. We carried out χ2 test, unconditional logistic regression analysis and crossover analysis to estimate the relationship between SNPs and lung cancer risk and the interaction between SNPs and smoking on susceptibility to lung cancer. The results indicated that rs1347093, rs1397529 polymorphisms were associated with lung cancer risk, especially with adenocarcinoma risk. Dominant genetic model of the rs1347093 was associated with reduced risk of lung cancer compared to CC genotype (AC+AA vs. CC: adjusted OR = 0.599, 95%CI = 0.418-0.858, P=0.005). For rs1347093, the similar result was found. Dominant genetic model of the rs1397529 was associated with reduced risk of lung cancer compared to AA genotype (AC+CC vs. AA: adjusted OR = 0.664, 95%CI = 0.491-0.897, P=0.008). There is no significant interaction between rs1347093, rs1397529 polymorphism and smoking on susceptibility to lung cancer. Our study might demonstrate that rs1347093 in MIR217HG and rs1397529 in Gab1 could be meaningful as the novel biomarker for lung cancer risk.

Genetic variation at the microRNA binding site of CAV1 gene is associated with lung cancer susceptibility.

Single nucleotide polymorphism (SNP) may influence the genesis and development of cancer in a variety of ways depending on their location. Here we conducted a study in Chinese female non-smokers to investigate the relationship between rs1049337, rs926198 and the risk or survival of lung cancer. Further, we explored whether rs1049337 could alter the binding affinity between the mRNA of CAV1 and the corresponding microRNAs. Finally, we evaluated the relationship between expression level of CAV1 and prognosis of lung cancer. The results showed that the rs1049337-C allele and rs926198-C allele were the protective alleles of lung cancer risk. Haplotype analysis indicated that the C-C haplotype (constructed by rs1049337 and rs926198) was a protective haplotype for lung cancer risk. The result of luciferase reporter assay showed that rs1049337 can affect the binding affinity of CAV1 mRNA to the corresponding microRNAs both in A549 cell line and H1299 cell line. Compared with C allele, T allele had a relatively decreased luciferase activity. Compared with paired normal adjacent tissue or normal lung tissue, lung cancer tissue showed a relatively low level of CAV1. Refer to those patients at early stage of lung cancer, the expression level of CAV1 in patients at late stage of lung cancer was relatively low. In conclusion, the results indicated that rs1049337, it's a SNP located at 3'UTR region of CAV1 may affect lung cancer risk by altering the binding affinity between the mRNA of CAV1 and the corresponding microRNAs.

Association of PPP1R13L and CD3EAP polymorphisms with risk and survival of non-small cell lung cancer in Chinese non-smoking females.

PPP1R13L and CD3EAP were confirmed to play important roles in transcription and apoptosis. SNPs in PPP1R13L and CD3EAP may be associated with lung cancer risk and survival. This study investigated the association of PPP1R13L rs1005165 and CD3EAP rs967591 with non-small cell lung cancer (NSCLC) risk and survival in Chinese non-smoking females. 442 NSCLC cases and 480 cancer-free controls were conducted in the case-control study, and 283 cases were in cohort study. Genotype was determined by Taqman real-time PCR. The statistical analyses were performed by SPSS 22.0 software. We found that rs1005165 and rs967591 were significantly associated with NSCLC risk in Chinese non-smoking females. For rs1005165, compared with homozygous wild CC genotype, carriers of CT or TT genotype had lower risk of NSCLC (adjusted ORs were 0.675 and 0.713, 95% CI were 0.461-0.988 and 0.525-0.968, respectively), adjusted OR for dominant model was 0.702, 95% CI was 0.526-0.937. For rs967591, AA genotype (adjusted OR = 0.721, 95% CI = 0.532-0.978) and at least one A allele (GA+AA) (adjusted OR = 0.716, 95% CI = 0.536-0.956) were significantly correlated with lower risk of NSCLC, compared with GG genotype. But we didn't find correlation between the two SNPs and survival time in Chinese non-smoking NSCLC females. In general, we found PPP1R13L rs1005165 and CD3EAP rs967591 might be associated with lower NSCLC risk in Chinese non-smoking females, but no significant relationship was found with NSCLC survival.

Polymorphisms of pri-miR-219-1 are associated with the susceptibility and prognosis of non-small cell lung cancer in a Northeast Chinese population.

Occurrence and development of non-small cell lung cancer (NSCLC) is a complex process affected both by gene and environment. Single nucleotide polymorphisms (SNPs) in microRNAs' (miRNAs) biogenesis influenced the expression of mature miRNAs, further had an impact on risk of NSCLC. Our study focused on the correlation between rs213210, rs421446 or rs107822 polymorphisms in pri-miR-219-1 and susceptibility or prognosis of NSCLC in Chinese. A case-control study of 405 new-diagnosis patients and 405 controls was performed. Ten ml venous blood from each subject was collected for genotype test via using TaqMan allelic discrimination methodology and SPSS was performed for statistical analyses. We found that CC genotype in rs213210 (OR=3.462, 95%CI=2.222-5.394, P<0.001) compared with TT genotype and GG genotype in rs107822 (OR=3.553, 95%CI=2.329-5.419, P<0.001) compared with AA genotype showed significantly increased risk of NSCLC. Haplotype analysis showed that pri-miR-219-1 haplotype Crs213210Crs421446Grs107822 was a dangerous haplotype for lung cancer. And polymorphisms in pri-miR-219-1 have showed no relationship with overall survival of NSCLC. Overall, these findings firstly showed that rs213210 and rs107822 could be meaningful as genetic markers for lung cancer risk.

Single nucleotide polymorphism rs3124599 in Notch1 is associated with the risk of lung cancer in northeast Chinese non-smoking females.

Lung cancer is one of the most common cancers and the main cause of cancer-related deaths. Notch1 might play a part in tumorigenesis of lung cancer. Here we explored the relationship of three SNPs (rs3124599, rs3124607 and rs3124594) in Notch1 with the risk and the survival of lung cancer in non-smoking females, including 556 cases and 395 controls. Chi-square tests, logistic regression analysis and crossover analysis were conducted to estimate the association between SNPs and the risk of lung cancer and the interaction between SNPs and environmental exposure. Survival analysis was conducted to explore the association between SNPs and survival of lung cancer. The results demonstrated that the polymorphism of rs3124599 was associated with the susceptibility of lung cancer in recessive model (AA+AG vs. GG). Compared to the those with AA or AG genotype, individuals with GG genotype had a 1.562-fold increased risk of lung cancer (P = 0.023, OR = 1.562, 95% CI = 1.062-2.297). In stratified analysis, the GG genotype of rs3124599 would increase the risk of small cell lung cancer (SCLC) (P = 0.011, OR = 2.167, 95% CI = 1.193-3.396). However, no significant interaction between rs3124599 and cooking oil fume exposure was observed either in addictive model or multiplicative model. The results of survival analysis showed there was no significant association between SNPs and prognosis of lung cancer (P = 0.949 for rs3124599, P = 0.508 for rs3124607, P = 0.884 for rs3124594). Our study might indicate that rs312599 in Notch1 may be a novel biomarker for SCLC risk in Chinese non-smoking females.