Chinese Non-smoking Females Research Articles

The clinical significance of endoplasmic reticulum stress related genes in non-small cell lung cancer and analysis of single nucleotide polymorphism for CAV1.

In recent years, protein homeostasis imbalance caused by endoplasmic reticulum stress has become a major hallmark of cancer. Studies have shown that endoplasmic reticulum stress is closely related to the occurrence, development, and drug resistance of non-small cell lung cancer, however, the role of various endoplasmic reticulum stress-related genes in non-small cell lung cancer is still unclear. In this study, we established an endoplasmic reticulum stress scores based on the Cancer Genome Atlas for non-small cell lung cancer to reflect patient features and predict prognosis. Survival analysis showed significant differences in overall survival among non-small cell lung cancer patients with different endoplasmic reticulum stress scores. In addition, endoplasmic reticulum stress scores was significantly correlated with the clinical features of non-small cell lung cancer patients, and can be served as an independent prognostic indicator. A nomogram based on endoplasmic reticulum stress scores indicated a certain clinical net benefit, while ssGSEA analysis demonstrated that there was a certain immunosuppressive microenvironment in high endoplasmic reticulum stress scores. Gene Set Enrichment Analysis showed that scores was associated with cancer pathways and metabolism. Finally, weighted gene co-expression network analysis displayed that CAV1 was closely related to the occurrence of non-small cell lung cancer. Therefore, in order to further analyze the role of this gene, Chinese non-smoking females were selected as the research subjects to investigate the relationship between CAV1 rs3779514 and susceptibility and prognosis of non-small cell lung cancer. The results showed that the mutation of rs3779514 significantly reduced the risk of non-small cell lung cancer in Chinese non-smoking females, but no prognostic effect was found. In summary, we proposed an endoplasmic reticulum stress scores, which was an independent prognostic factor and indicated immune characteristics in the microenvironment of non-small cell lung cancer. We also validated the relationship between single nucleotide polymorphism locus of core genes and susceptibility to non-small cell lung cancer.

CN16 Lung cancer risk prediction nomogram in Chinese female non-smokers

About 53% of lung cancers in females are not attributable to smoking worldwide. The aim was to develop and validate a simple and non-invasive model which could assess and stratify lung cancer risk in female non-smokers in China. A large-sample size, population-based study was conducted under the framework of a population-based Cancer Screening Program in Urban China (CanSPUC). Data on the lung cancer screening in Henan province, China, from October 2013 to October 2019 were used and randomly divided into the training and validation sets. Related risk factors were identified through multivariable Cox regression analysis, followed by establishment of risk prediction nomogram. Discrimination [area under the curve (AUC)] and calibration were further performed to assess the validation of risk prediction nomogram in the training set, and then validated by the validation set. A total of 151,834 eligible subjects were included, with a mean age of 55.34 years. Subjects were randomly divided into the training (75,917) and validation (75,917) sets. Elder age, history of chronic respiratory disease, first-degree family history of lung cancer, menopause, and history of benign breast disease were the independent risk factors for lung cancer. Using these five variables, we plotted 1-year, 3-year, and 5-year lung cancer risk prediction nomogram. The AUC was 0.762, 0.718, and 0.703 for the 1-, 3- and 5-year lung cancer risk in the training set, respectively. In the validation set, the model showed a good predictive discrimination, with the AUC was 0.646, 0.658, and 0.650 for the 1-, 3- and 5-year lung cancer risk. We developed and validated a simple and non-invasive lung cancer risk model in female non-smokers. This model can be applied to identify and triage patients at high risk for developing lung cancers in female non-smokers.

OA13.05 Lung Cancer Risk Prediction Nomogram in Chinese Female Non-smokers

About 53% of lung cancers in females are not attributable to smoking worldwide. The aim was to develop and validate a simple and non-invasive model which could assess and stratify lung cancer risk in female non-smokers in China.

Lung cancer risk prediction nomogram in Chinese female non-smokers.

10530 Background: About 53% of lung cancers in females are not attributable to smoking worldwide. The aim was to develop and validate a simple and non-invasive model which could assess and stratify lung cancer risk in female non-smokers in China. Methods: A large-sample size, population-based study was conducted under the framework of a population-based Cancer Screening Program in Urban China (CanSPUC). Data on the lung cancer screening in Henan province, China, from October 2013 to October 2019 were used and randomly divided into the training and validation sets. Related risk factors were identified through multivariable Cox regression analysis, followed by establishment of risk prediction nomogram. Discrimination [area under the curve (AUC)] and calibration were further performed to assess the validation of risk prediction nomogram in the training set, and then validated by the validation set. Results: A total of 151,834 eligible subjects were included, with a mean age of 55.34 years. Subjects were randomly divided into the training (75,917) and validation (75,917) sets. Elder age, history of chronic respiratory disease, first-degree family history of lung cancer, menopause, and history of benign breast disease were the independent risk factors for lung cancer. Using these five variables, we plotted 1-year, 3-year, and 5-year lung cancer risk prediction nomogram. The AUC was 0.762, 0.718, and 0.703 for the 1-, 3- and 5-year lung cancer risk in the training set, respectively. In the validation set, the model showed a good predictive discrimination, with the AUC was 0.646, 0.658, and 0.650 for the 1-, 3- and 5-year lung cancer risk. Conclusions: We developed and validated a simple and non-invasive lung cancer risk model in female non-smokers. This model can be applied to identify and triage patients at high risk for developing lung cancers in female non-smokers.

Lung cancer risk in non-smoking females with a familial history of cancer: a multi-center prospective cohort study in China

Familial risk of lung cancer has been widely studied but whether this association holds in non-smoking females is largely unknown. We sought to determine the relationship between a family history of cancer and lung cancer risk among Chinese non-smoking females based on a multi-center prospective population-based cohort study involving 547,218 individuals between 2013 and 2019. A total of 1620 lung cancer cases occurred during a median follow-up of 3.9 years. Multivariable Cox regression showed that a family history of lung cancer in first-degree relatives significantly increased the risk of lung cancer (HR: 1.50, 95%CI: 1.29, 1.75, P<0.001). Relative to those with no relatives affected, the risk of lung cancer was 51% higher in females with one relative affected (HR: 1.51, 95%CI: 1.29-1.76, P<0.001), 123% higher in females with two relatives affected (HR: 2.23, 95%CI: 1.57-3.15, P<0.001) and 143% higher in females with three or more relatives affected (HR: 2.43, 95%CI: 1.21-4.91, P=0.013). Two nested case control studies stratified by age at diagnosis were conducted to verify potential disparities in this association between the early or late onset of lung cancer. A family history of lung cancer in first-degree relatives was significantly correlated with an elevated risk of lung cancer for both cases before and after age 65 (OR: 1.36, 95%CI: 1.07-1.74, P=0.013; OR: 1.64, 95%CI: 1.15-2.33, P=0.006). Our analysis confirmed the importance of familial history of cancers on lung cancer risk in non-smoking females and highlighted the possibility of interaction between genetic and environmental effect on lung cancer.

Polymorphisms in Neuronal Growth Regulator 1 and Otoancorin Alternate the Susceptibility to Lung Cancer in Chinese Nonsmoking Females.

Cell adhesion molecules (CAMs) play crucial roles in the genesis and progress of tumor. We investigated the effects of single nucleotide polymorphisms (SNPs) of CAMs, neuronal growth regulator 1 (NEGR1), and Otoancorin (OTOA) on lung cancer susceptibility in Chinese nonsmoking females. Logistic regression and Cox regression analyses were conducted to investigate the effects of SNPs and environmental factors. For rs3102911, genotype TT carriers decreased the risk of lung cancer with an odds ratio (OR) of 0.635. AA genotypes of rs741718 increased the risk of lung cancer with an OR of 3.527. In stratified analysis, genotype AA carriers of rs741718 had a high susceptibility to lung adenocarcinoma compared with GG and AG genotypes. Analyses of association between SNPs and clinical characteristics revealed that rs3102911 as a protective factor and rs741718 as a risk factor influenced the lung cancer occurrence and progression in nonsmoking females.

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.

Polymorphisms of rs4787050 and rs8045980 are associated with lung cancer risk in northeast Chinese female nonsmokers.

Aim: We studied the association between two single-nucleotide polymorphisms (SNPs: rs4787050 and rs8045980) in RBFOX1 and lung cancer risk, and explored the interaction between the two SNPs and exposure to cooking oil fume on lung cancer risk in northeast Chinese female nonsmokers. Methods: Northeast Chinese female nonsmokers were enrolled into the study (people with lung cancer, 647; people without lung cancer, 675). All statistical analyses were performed using SPSS software. Results: The SNPs rs4787050 and rs8045980 showed a significant association with susceptibility to lung cancer. Moreover, cooking oil fume exposure was found to increase the risk of lung cancer. However, no gene-environment interactions were discovered. Conclusion: The present study revealed that rs4787050 and rs8045980 in RBFOX1 may be meaningful as a novel biomarker for lung cancer susceptibility.

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.

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.

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.

MiR-196a2 and lung cancer in Chinese non-smoking females: a genetic association study and expression analysis.

BackgroundThe common polymorphism rs11614913 in miR-196a2 might be associated with lung cancer risk for non-smoking females in northeast China.MethodsThe genotypes of rs11614913 in miR-196a2 were determined by a case-control study including 1003 patients with lung cancer and 1003 healthy controls. The tissues were detected to assess the miRNA expression. Secondary structures of miR-196a2 were predicted.ResultsThere was a significant association between miR-196a2 rs11614913 and lung cancer risk in Chinese non-smoking females. Individuals carrying TC or CC genotype had increased risk of lung cancer compared with TT genotype (adjusted risks were 1.63 and 1.67). The C allele was associated with a higher risk of lung cancer with a significant risk of 1.27. The similar significant results were also found in lung adenocarcinoma. There was a significant association between miR-196a2 expression and lung cancer risk (t=2.594, P=0.012). The relative expression of miR-196a2 was significantly higher for CC genotype comparing with the CT or TT genotype in tumor tissues (P values were all 0.003). The optimal free energies were different for T allele and C allele.ConclusionsThe polymorphism rs11614913 in miR-196a2 may be associated with lung cancer risks in Chinese non-smoking females through affecting miR-196a2 expression and secondary structure.

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

Multiple functional SNPs in differentially expressed genes modify risk and survival of non-small cell lung cancer in Chinese female non-smokers.

DNA genotype can affect gene expression, and gene expression can influence the onset and progression of diseases. Here we conducted a comprehensive study, we integrated analysis of gene expression profile and single nucleotide polymorphism (SNP) microarray data in order to scan out the critical genetic changes that participate in the onset and development of non-small cell lung cancer (NSCLC). Gene expression profile datasets were downloaded from the GEO database. Firstly, differentially expressed genes (DEGs) between NSCLC samples and adjacent normal samples were identified. Next, by STRING database, protein-protein interaction (PPI) network was constructed. At the same time, hub genes in PPI network were identified. Then, some functional SNPs in hub genes that may affect gene expression have been annotated. Finally, we carried a study to explore the relationship between functional SNPs and NSCLC risk and overall survival in Chinese female non-smokers. A total of 488 DEGs were identified in our study. There are 29 proteins with a higher degree of connectivity in the PPI network, including FOS, IL6 and MMP9. By using database annotation, we got 8 candidate functional SNPs that may affect the expression level of hub proteins. In the case-control study, we found that rs4754-T allele, rs959173-C allele and rs2239144-G allele were the protective allele of NSCLC risk. In dominant model, rs4754-CT+TT genotype were associated with a shorter survival time. In general, our study provides a novel research direction in the field of multi-omic data integration, and helps us find some critical genetic changes in disease.

MiR-146a polymorphism correlates with lung cancer risk in Chinese nonsmoking females.

This study provides evidence that the common rs2910164 polymorphism in miR-146a strongly correlates with lung cancer risk in nonsmoking females in northeast China. The genotypes of miR-146a rs2910164 were determined in 1131 patients with lung cancer and 1003 healthy control subjects. Tissue samples were used to evaluate the association between miRNA expression and lung cancer risk as well as the correlation between rs2910164 genotypes and miR-146a expression. The secondary structures of the wild-type and variant miR-146a sequences were predicted, and luciferase-based target assays were used to test whether miR-146a bound to tumor necrosis factor receptor associated factor 6 (TRAF6) mRNA. Individuals carrying heterozygous CG genotype of miR-146a rs2910164 had less risk of lung cancer than those carrying homozygous wild CC genotype (OR = 0.76, 95% CI = 0.60-0.98, P = 0.032). We found no significant association between miR-146a expression and lung cancer risk. MiR-146a expression differed in those carrying the CC genotype as compared with the CG or the GG genotype (P = 0.032 and 0.001), and the secondary structure of the C allele differed slightly from the G allele. Significantly lower levels of luciferase activity were observed when the TRAF6 3′UTR was cotransfected with miR-146a-3p carrying the rs2910164 C allele (P = 0.001). Thus, miR-146a rs2910164 polymorphism may influence susceptibility to lung cancer in Chinese nonsmoking females through targeting TRAF6.

Association of MicroRNA-149 Polymorphism with Lung Cancer Risk in Chinese Non-Smoking Female: A Case-Control Study.

IntroductionRs2292832 is a single nucleotide polymorphism located in the precursor of mir-149 and was reported to be associated with varieties of malignancies. So far, the effect of miR-149 rs2292832 polymorphism on lung cancer risk was unclear. In addition, cooking oil fume exposure was demonstrated to be an important environmental risk factor in Chinese female. The aim of the present study was to evaluate the associations of rs2292832 polymorphism, cooking oil fume exposure and multiplicative interaction of cooking oil fume exposure and rs2292832 polymorphism with lung cancer risk in Chinese non-smoking female population.MethodsThe present study was a hospital-based case-control study conducted in Chinese non-smoking females. 555 lung cancer patients and 395 cancer-free controls were interviewed to collect demographic data and exposure status of environmental risk factors, and then donate 10 ml venous blood which was used to be genotyped by Taqman allelic discrimination method. The statistical analyses were performed on SPSS 13.0 software.ResultsThe association between miR-149 rs2292832 polymorphism and risk of lung cancer(TC vs. TT: OR = 1.006, 95%CI = 0.767–1.321, P = 0.963; CC vs. TT: OR = 0.41, 95%CI = 0.532–1.329, P = 0.458; Dominant model: OR = 0.965, 95%CI = 0.745–1.251, P = 0.788; Recessive model: OR = 0.816, 95%CI = 0.528–1.259, P = 0.357, adjusted for age), non-small cell lung cancer(TC vs. TT: OR = 1.006, 95%CI = 0.767–1.321, P = 0.963; CC vs. TT: OR = 0.841, 95%CI = 0.532–1.329, P = 0.458, adjusted for age), lung adenocarcinoma(TC vs. TT: OR = 0.944, 95%CI = 0.700–1.273, P = 0.707; CC vs. TT: OR = 0.801, 95%CI = 0.485–1.323, P = 0.386, adjusted for age) and squamous cell carcinoma(TC vs. TT: OR = 1.025, 95%CI = 0.641–1.638, P = 0.919; CC vs. TT: OR = 0.792, 95%CI = 0.346–1.813, P = 0.581, adjusted for age) were all not statistically significant. Result of Logistic regression showed that the multiplicative interaction of cooking oil fume exposure and rs2292832 polymorphism was not statistically significant (P = 0.063 for lung cancer and P = 0.064 for lung adenocarcinoma).ConclusionMicroRNA-149 rs2292832 polymorphism may not be associated with lung cancer risk in Chinese non-smoking female.

Polymorphisms in miR-135a-2, miR-219-2 and miR-211 as well as their interaction with cooking oil fume exposure on the risk of lung cancer in Chinese nonsmoking females: a case-control study.

BackgroundThe associations between microRNAs and lung cancer have received increasing attention. This study assess the association between polymorphisms in miR-135a-2, miR-219-2 and miR-211 genes and the risk of lung cancer, as well as the gene–environment interaction between these polymorphisms and cooking oil fume exposure.MethodsA case–control study featuring 268 cases and 266 controls was conducted. The associations of miR-135a-2 rs10459194, miR-219-2 rs10988341 and miR-211 rs1514035 polymorphisms with the risk of lung cancer were analyzed. The gene–environment interactions were also reported on both additive and multiplicative scales.ResultsThere were no statistically significant associations between the single-nucleotide polymorphisms (SNPs) and lung cancer or lung adenocarcinoma. The individuals with both a risk genotype of miRNA SNPs and exposure to a risk factor (cooking oil fumes) were at higher risk of lung cancer than those with only one of these two risk factors (odd ratios of 2.208, 1.285 and 1.813 for miR-135a-2 rs10459194; 2.164, 1.209 and 1.806 for miR-219-2 rs10988341; and 2.122, 1.146 and 1.725 for miR-211 rs1514035, respectively). However, the measures of biological interaction indicate that there was no such interaction between the three SNPs and exposure to cooking oil fumes on an additive scale. Logistic regression models also suggested that the gene–environment interactions were not statistically significant on a multiplicative scale.ConclusionsThere were no significant associations between the polymorphisms in miRNAs (miR-26a-1 rs7372209, miR-605 rs2043556 and miR-16-1 rs1022960) and the risk of lung cancer in the Chinese nonsmoking female population. The interactions between these polymorphisms in miRNAs and cooking oil fume exposure were also not statistically significant.

Association between polymorphisms in pre-miRNA genes and risk of lung cancer in a Chinese non-smoking female population

BackgroundMicroRNAs play important roles in the development of human chronic diseases including lung cancer. This is the first case-control study of lung cancer in a non-smoking female population in northeast China, to evaluate the roles of the polymorphisms in pre-miRNAs on risk of lung cancer. MethodsThe genotypes of six polymorphisms in miRNAs were determined in 575 patients with lung cancer and 608 healthy controls who were frequency matched for age. ResultsFor miR-146a rs2910164, individuals carrying heterozygous CG or homozygous GG genotype had decreased risks of lung cancer compared with those carrying homozygous wild CC genotype (adjusted odds ratios were 0.76 and 0.64, 95% confidence intervals were 0.59–0.99 and 0.46–0.90, P values were 0.039 and 0.010, respectively). G allele of rs2910164 was associated with a lower risk of lung cancer with a significant odds ratio of 0.80. MiR-423 rs6505162CA or AA genotype was associated with significantly decreased risk for lung cancer compared to CC genotype (adjusted odds ratios were 0.77 and 0.54). The significant result was also found in the allele model with odds ratio of 0.75. However, miR-196a2 rs11614913, miR-30c-1 rs928508, miR-608 rs4919510 and miR-27a rs895819 polymorphisms were not significantly associated with lung cancer risks in any models. The similar results were also found in lung adenocarcinoma patients. ConclusionsThese findings suggest that miR-146a rs2910164C>G and miR-423 rs6505162C>A polymorphisms may contribute to genetic susceptibility to lung cancer and lung adenocarcinoma in Chinese non-smoking females.

TGFβ-1 and TGFBR2 polymorphisms, cooking oil fume exposure and risk of lung adenocarcinoma in Chinese nonsmoking females: a case control study.

BackgroundTransforming growth factor-β (TGF-β) plays an important role in regulating cellular functions, and many studies have demonstrated important roles for TGF-β in various cancers. Single nucleotide polymorphisms (SNPs) of TGF-β may influence lung carcinogenesis. The aim of this study was to test whether TGF-β1 C509T and TGF-β receptor II (TGFBR2) G-875A polymorphisms were associated with lung adenocarcinoma in nonsmoking females.MethodsA hospital-based case–control study was performed in Chinese nonsmoking females. Genotyping was performed using TaqMan SNP genotyping assay, and demographic data and environmental exposure were collected by trained interviewers after informed consents were obtained.ResultsA total of 272 (95.4%) cases and 313 (99.4%) controls were successfully genotyped, and the results showed that the polymorphic allele frequencies of C509T and G875A were similar among lung adenocarcinoma patients and controls (P=0.589 and 0.643, respectively). However, when the data were stratified for cooking oil fume exposure, the TT genotype of the TGFB1 C509T polymorphism showed a significantly decreased risk for lung adenocarcinoma compared with the CC genotype (adjusted OR=0.362, 95% CI=0.149–0.878, P=0.025).ConclusionsTGF-β1 gene C509T polymorphism might be associated with decreased risk of lung adenocarcinoma in Chinese females exposed to cooking oil fumes, but no association was observed TGFBR2 gene G875A polymorphism.