Zhihua Yin

Rs2292832 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. The 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. The 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). MicroRNA-149 rs2292832 polymorphism may not be associated with lung cancer risk in Chinese non-smoking female.

The 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. A 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. There 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. There 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.

MicroRNA biosynthesis genes can affect the regulatory effect of global microRNAs to target mRNA and hence influence the genesis and development of human cancer. Here, we selected five single nucleotide polymorphisms (SNPs) (rs7813, rs2740349, rs2291778, rs910924, rs595961) in two key microRNA biosynthesis genes (GEMIN4 and AGO1) and systematically evaluated the association between these SNPs, the gene-environment interaction and lung cancer risk. To control the impact of cigarette smoking on lung cancer, we recruited Chinese female non-smokers for the study. The total number of lung cancer cases and cancer-free controls were 473 and 395 in the case-control study. Four SNPs showed statistically significant associations with lung cancer risk. After Bonferroni correction, rs7813 and rs595961 were evidently still associated with lung cancer risk. In the stratified analysis, our results revealed that all five SNPs were associated with the risk of lung adenocarcinoma; after Bonferroni correction, significant association was maintained for rs7813, rs910924 and rs595961. Haplotype analysis showed GEMIN4 haplotype C-A-G-T was a protective haplotype for lung cancer. In the combined unfavorable genotype analysis, with the increasing number of unfavorable genotypes, a progressively increased gene-dose effect was observed in lung adenocarcinoma. We also found that individuals exposed to cooking oil fumes showed a relatively high risk of lung cancer, but no interactions were found between cooking oil fume exposure or passive smoking exposure with these SNPs, either on an additive scale or a multiplicative scale. Overall, this is the first study showing that rs7813 and rs595961 could be meaningful as genetic markers for lung cancer risk.

LAPTM4B is a newly cloned gene that shows an active role in many solid tumors progression in substantial researches, mainly through the autophage function. Accumulated studies have been conducted to determine the association of LAPTM4B polymorphism with cancer risk. While the results are inconsistent, we conducted the meta-analysis to determine the strength of the relationship. Results showed that allele*2 carriers exhibited a significantly increased risk of cancer development with comparison to allele*1 homozygote (for *1/2, OR = 1.55, 95% CI 1.367-1.758; for *2/2, OR = 2.093, 95%CI 1.666-2.629; for *1/2 + *2/2, OR = 1.806, 95%CI 1.527-2.137). We also observed a significant association between *2/2 homozygote and cancer risk with comparison to allele*1 containing genotypes (OR = 1.714, 95%CI 1.408-2.088). Allele*2 is a risk factor for cancer risk (OR = 1.487, 95%CI 1.339-1.651). Stratified analysis by tumor type exhibits the significant association of this genetic variants with various cancers. In conclusion, LAPTM4B polymorphism is associated with cancer risk and allele*2 is a risk factor.

Transforming 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. A 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. A 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). TGF-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.

Lung adenocarcinoma is a heterogernous disease that creates challenges for classification and management. The purpose of this study is to identify specific miRNA markers closely associated with the survival of LUAD patients from a large dataset of significantly altered miRNAs, and to assess the prognostic value of this miRNA expression profile for OS in patients with LUAD.

Excision repair cross-complementing group 2 (ERCC2) plays important roles in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of ERCC2 gene are suspected to influence the risks of oral cancer. We performed a meta-analysis to systematically summarize the possible association of ERCC2 rs1799793 and rs13181 polymorphisms with oral cancer risks.

MicroRNAs (miRNAs) are a class of new non-coding RNA, which may play a more important role in the pathogenesis of human cancers. Rs2910164 in miR-146a and rs3746444 in miR-499 are shown to be associated with increased/decreased cancer risk. We performed a meta-analysis to systematically summarize the possible association. We retrieved the relevant articles from PubMed databases. Studies were selected using specific inclusion and exclusion criteria. ORs and 95% CIs were calculated to access the strength of association between microRNA polymorphism and cancer risk. All analyses were performed using the Stata software. Twenty-nine studies were included in this meta-analysis. There were not significant associations between miR-146a rs2910164 and miR-499 rs3746444 polymorphisms with overall cancer risk. In the subgroup analysis by ethnicity, significantly affected cancer risks were found among Asians for both rs2910164 (GC vs. GG: OR = 0.89, 95% CI = 0.82–0.96; CC vs. GG: OR = 0.80, 95% CI = 0.66–0.97; GC + CC vs. GG: OR = 0.86, 95% CI = 0.76–0.97; C vs. G: OR = 0.91, 95% CI = 0.82–1.00) and rs3746444 (GG + AG vs. AA: OR = 1.21, 95% CI = 1.00–1.46). In the tumor type subgroup analysis, rs2910164 C allele decreased the risk of hepatocellular carcinoma (C vs. G: OR = 0.89, 95% CI = 0.80–1.00) and cervical squamous cell carcinoma (C vs. G: OR = 0.72, 95% CI = 0.62–0.84). The rs2910164 in miR-146a and the rs3746444 in miR-499 are likely to be associated with cancer risk.

Background: Lung cancer is the major cause of cancer death globally, it is often diagnosed at an advanced stage and has one of the lowest survival rates of any type of cancer. The common interest in the field of lung cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. There is increasing evidence to suggest that microRNAs play important and complex roles in lung cancer. Methods: A meta-analysis was conducted to review the published microRNA expression profiling studies that compared the microRNAs expression profiles in lung cancer tissues with those in normal lung tissues. A vote-counting strategy that considers the total number of studies reporting its differential expression, the total number of tissue samples used in the studies and the average fold change was employed. Results: A total of 184 differentially expressed microRNAs were reported in the fourteen microRNA expression profiling studies that compared lung cancer tissues with normal tissues, with 61 microRNAs were reported in at least two studies. In the panel of consistently reported up-regulated microRNAs, miR-210 was reported in nine studies and miR-21 was reported in seven studies. In the consistently reported down-regulated microRNAs, miR-126 was reported in ten studies and miR-30a was reported in eight studies. Four up-regulated microRNAs (miR-210, miR-21, miR-31 and miR-182) and two down-regulated mcroiRNAs (miR-126 and miR-145) were consistently reported both in squamous carcinoma and adenocarcinoma-based subgroup analysis, with the other 14 microRNAs solely reported in one or the other subset. Conclusions: In conclusion, the top two most consistently reported up-regulated microRNAs were miR-210 and miR-21. The results of this meta-analysis of human lung cancer microRNA expression profiling studies might provide some clues of the potential biomarkers in lung cancer. Further mechanistic and external validation studies are needed for their clinical significance and role in the development of lung cancer.