Studies on lithium in the environment and its effects on the central nervous system / 中华预防医学杂志

This paper introduces the distribution of global lithium resources and absorption, distribution, metabolism and excretion of lithium in the human body, discussing the positive effect of lithium in the environment on the nervous system and its neuroprotective mechanism. The tiny amounts of lithium that enter the body through the food chain have been linked to beneficial health effects, such as improved cognition and reduced depression and violence. However, the safe dose range of lithium is narrow, and the health effects of drinking high concentrations of lithium water in high-lithium areas are unclear. It is necessary to study the health effects and mechanisms of different doses of lithium, especially high concentrations of lithium in the environment.

Lung cancer and its epigenetics association with chronic obstructive pulmonary disease / 中华医学遗传学杂志

Lung cancer and chronic obstructive pulmonary disease (COPD) are the leading causes of morbidity and mortality worldwide. Development of lung cancer involves both genetic and environment factors. In addition to genetic alterations, epigenetic mechanism is closely involved in pathogenesis of lung cancer. Characterized by an abnormal persistent inflammatory response to noxious environmental stimulation, COPD has shown to increase the susceptibility for lung tumorigenesis in previous research. Current research on epigenetics of lung cancer and COPD has focused on aberrant DNA methylation, histone acetylation and non-coding RNAs regulation. The aberrant DNA methylation associated with lung cancer and COPD has included overexpression of DNA methyltransferase, global DNA hypomethylation and DNA hypermethylation in promoter regions, while histone acetylation and histone methylation are the major changes for histone modification, in which histone acetyltransferases, histone deacetylases, histone methyltransferases and histone demethylases play the most important roles. RNA interference and microRNAs are both hot topics of research on non-coding RNAs regulation. Understanding of concurrent epigenetic alterations in the pathogenesis of lung cancer and COPD may facilitate identification of specific therapeutic targets and development of effective treatment.

Effects of CYP1A1 and GSTM1 gene polymorphisms and BPDE-DNA adducts on lung cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the effect of CYP1A1 and GSTM1 genetic polymorphisms and BPDE-DNA adducts on lung tumorigenesis.</p><p><b>METHODS</b>The case control study has included 200 cases of lung cancer and 200 controls. DNA was extracted from blood samples of all subjects. The genotype of both CYP1A1 and GSTM1 were detected with PCR-based restriction fragment length polymorphisms (PCR-RELP). BPDE-DNA adducts were detected with competitive ELISA.</p><p><b>RESULTS</b>CYP1A1 mutant genotype and GSTM1 null genotype with smoke has increased the risk of lung cancer, with OR being 2.406(1.321-4.382), 2.755(1.470-5.163), respectively. The level of BPDE-DNA adducts in patients was greater than control, and the adduct level in ever smokers was higher than never smokers, the difference was statistically significant (P= 0.0252). GSTM1 null genotype individuals with BPDE-DNA level higher than 5 adducts/10(8) nucleotide have increased risk of lung cancer (OR= 1.988, 95%CI: 1.011-3.912). Compared with never smokers with CYP1A1 wild genotype, smokers with CYP1A1 mutation genotype had an increased risk of forming a higher level of DNA adducts (P= 0.0459). Smokers with GSTM1 null genotype formed more DNA adducts compared with never smokers with GSTM1 functional genotype (OR = 2.432, 95% CI: 1.072-4.517).</p><p><b>CONCLUSION</b>GSTM1 null genotype with higher level DNA adducts may increase the risk of lung cancer. DNA adducts form easier in smokers with CYP1A1 mutation genotype and GSTM1 null genotype, which in turn may influence lung tumorigenesis.</p>

Correlation between RARbeta gene promoter methylation and P53 gene mutations in non-small cell lung cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the correlation between RARbeta gene promoter methylation and P53 gene mutations in non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Promoter methylation of RARbeta and P53 mutations of exons 5 through 9 in 198 resected primary NSCLC tissues were determined by methylation-specific PCR and direct sequencing.</p><p><b>RESULTS</b>RARbeta gene promoter methylation and P53 mutation were detected in 58.1% and 36.4% of tumors, respectively. Both were higher in males than in females and in smokers than in nonsmokers. A higher prevalence of RARbeta promoter methylation was found in patients with advanced stage tumors than those with TNM stage I. P53 gene mutations were more frequent in squamous cell carcinoma and adeno-squamous carcinoma than adenocarcinoma. All such differences were statistically significant (P< 0.05). Frequencies of P53 mutations, including G:C>T:A mutations, transversions and missense mutations were significantly higher in tumors with RARbeta methylation than in those without (P< 0.05). A significantly higher prevalence of RARbeta methylation was found in tumors with only G:C>T:A mutation in P53 gene than those without P53 mutations (P< 0.05). This difference (OR=3.737, 95%CI: 1.414-9.873) was still statistically significant (P< 0.05) in smokers (OR=4.020, 95%CI: 1.263-12.800), squamous cell carcinomas (OR=5.480, 95%CI: 1.400-21.446) or patients with advanced tumors (OR=3.446, 95%CI: 1.054-11.267) after adjusting for age and sex.</p><p><b>CONCLUSION</b>RARbeta methylation is associated with G:C>T:A mutations in P53 gene in NSCLC.</p>

Effects of 5-Aza-2-deoxycytidine on DNA methylation of anti-oncogenes in non-small cell lung cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the expression of SFRP1 gene methylation in non-small cell lung cancer (NSCLC), and study the effect of 5-Aza-2-deoxycytidine (5-Aza-CdR) on DNA methylation and expression of SFRP1, p16 and MGMT genes in the human lung cancer cell line SPC-A-1 cells.</p><p><b>METHODS</b>SP immunohistochemistry and methylation-specific PCR were used to detect the SFRP1 methylation in 60 NSCLC cases, and 21 cases of benign lung diseases were used as control group. SPC-A-1 cells were cultured and treated with 5-Aza-CdR. The promoter methylation status of SFRP1, p16 and MGMT genes were detected by methylation-specific polymerase (MSP) chain reaction, and mRNAs were detected by real-time PCR.</p><p><b>RESULTS</b>The positive rate of SFRP1 gene methylation in NSCLC was significantly higher than that in normal lung tissue (58.3% vs. 14.3%; χ(2) = 12.118, P = 0.001). SFRP1 gene methylation was closely correlated with lymph node metastasis and degree of differentiation in NSCLC (P < 0.05). SFRP1 protein expression was correlated with clinical stage, degree of differentiation and lymph node metastasis in NSCLC (P < 0.05). The positive expression of SFRP1 protein in 30 cases of NSCLC tissue containing SFRP1 gene methylation was significantly higher than that in non-methylated NSCLC (68.6% vs. 24.0%; χ(2) = 9.613, P = 0.002). SFRP1 gene methylation was closely correlated with SFRP1 gene protein expression in NSCLC (P < 0.05). Negative expression of SFRP1 protein was correlated with the differentiation, clinical stage, and lymph node metastasis in NSCLC (all P < 0.05). Without 5-Aza-CdR treatment, the expressions of methylation of SFRP1, p16 and MGMT genes and their mRNA were low. After 5-Aza-CdR treatment at different concentrations, their expressions were significantly elevated (all P < 0.05).</p><p><b>CONCLUSIONS</b>SFRP1 gene methylation is closely associated with carcinogenesis and development of NSCLC. 5-Aza-CdR may reverse the methylation of SFRP1, p16 and MGMT genes, and facilitate the re-expression of the anti-oncogenes.</p>

Relationship between promoter methylation of p16, DAPK and RAR beta genes and the clinical data of non-small cell lung cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the effects of promoter methylation of p16, death-associated protein kinase (DAPK) and retinoic acid receptor-beta (RAR beta) genes on clinical data in non-small cell lung cancers, and to study the effect of smoking on the risk of gene methylation.</p><p><b>METHODS</b>The promoter methylation of p16, DAPK and RAR beta genes in 200 primary non-small cell lung cancers and the corresponding nonmalignant lung tissues were determined by methylation-specific PCR.</p><p><b>RESULTS</b>Methylation in the tumor tissues was detected in 51.0% for p16, 60.0% for DAPK, and 58.0% for RAR beta gene, with significant differences (P < 0.05) when compared with those in the corresponding nonmalignant tissues(12.5%, 11.5% and 15.0%) respectively. p16 gene methylation in tumor tissue was associated with age significantly in unconditional logistic regression analysis (P < 0.01) and histologic type (P < 0.05). DAPK gene methylation in tumor tissue was associated significantly with age (P < 0.05), gender (P < 0.05) and clinical type (P < 0.05). RAR beta gene methylation in tumor tissue was associated with clinical type (P < 0.05) and tumor stage (P < 0.05) significantly. The interaction odds ratio (OR) for the gene-gene interaction in tumor tissue between p16 and DAPK was 1.987 (95%CI:1.055-3.743). The results of the gene-smoking analyses revealed that a relationship existed between cigarette smoking and p16 gene methylation (OR = 3.139, 95%CI: 1.046-9.419), the OR for the relationship of DAPK gene methylation and cigarette smoking was 3.585(95%CI: 1.270-10.123) in tumor tissue. The RAR beta gene methylation did not differ based on the smoking status of patients in tumor tissue.</p><p><b>CONCLUSION</b>The p16, DAPK and RAR beta genes methylation are strongly associated with clinical data of non-small cell lung cancer, and methylation of p16 and DAPK genes are associated with tobacco smoking.</p>

Current progress in research on epigenetic effects of air pollution / 浙江大学学报·医学版

Air pollution is associated with numerous diseases. In recent years,researches have increasingly showed that epigenetic modifications usually occur at the early stage of diseases, and make greater contributions to the occurrence and development of diseases compared to genetic abnormalities. Thus, researches on epigenetic effects of air pollution would serve for better understanding the interaction between air pollutants and genome in the pathogenesis of disease. Meanwhile, in order to reduce the exposure to air pollution and diminish the adverse effects related, further studies are needed to identify epigenetic biomarkers of air pollution so that we can take timely and effective measures in disease prevention.