OBJECTIVETo investigate the possible association between dopamine D2 receptor (DRD2) TaqI A and TaqI B genotypes as well as smoking behavior and the risk of lung cancer among Chinese Han people.

METHODSPCR was used to perform genotyping on peripheral WBC DNA from 326 lung cancer patients and 326 age, sex and ethnicity-matched healthy controls. Subjects were interviewed to obtain relevant information and lifetime history of tobacco use.

RESULTSThere were no statistically significant differences in the distribution of DRD2 genotypes between lung cancer cases and controls. The DRD2 genotypes and smoking status showed no correlation among cases and among controls as well. However, among controls, the frequency of the DRD2 * A2/A2 genotype in smokers who smoked > or = 25 cigarettes/day appeared to be higher than that in those who smoked < 25 cigarettes/day (42.5% versus 26.1%, P = 0.047). A similar trend was also found for the DRD2 * B2/B2 genotype, which was linked to the DRD2 * A2/A2 genotype, although the difference was not significant (40.0% versus 26.1%, P = 0.091). In contrast to controls, no association was found between the DRD2 genotypes and smoking among lung cancer cases.

CONCLUSIONOur results suggested that DRD2 * A2/A2 genotype might be associated with a greater smoking intensity in Chinese. Further studies are needed to confirm this preliminary finding.

Aged ; Female ; Humans ; Lung Neoplasms ; etiology ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Dopamine D2 ; genetics ; Smoking ; adverse effects

OBJECTIVE: To investigate the mechanism of activator protein-1 (AP-1) on cigarette smoke-induced airway mucous hypersecretion and to explore the possible signal transduction pathway that activates AP-1. METHODS: The airway epithelial cell line (BEAS-2B) was cultured in vivo and treated with cigarette smoke extract (CSE). The DNA binding activity of AP-1 was blocked by the transfection of c-Jun dominant negative mutant TAM67 into the cells. SP600125 and PD98059 were used to block the activation of c-Jun terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) respectively. MUC5AC protein was detected by enzyme-linked immunosorbent assay, MUC5AC mRNA level was analyzed by RT-PCR, while the protein contents of p-JNK, p-ERK and p-P38 were detected by Western blot, and the DNA binding activity of AP-1 was determined by electrophoretic mobility shift assay. RESULTS: The MUC5AC protein production and mRNA expression in the CSE group were significantly higher than those in the control group, and the DNA binding activity of AP-1 was also higher than that in the control group (P<0.01). The protein contents of p-ERK and p-JNK in the CSE group were higher than those in the control group (P<0.01), but the p-P38 level was not significantly different from that in the control group (P>0.05). After the transfection of TAM67 into the cells, the expression levels of MUC5AC protein and mRNA and the binding activity of AP-1 decreased significantly (P<0.01). The DNA binding activity of AP-1 and the expression levels of MUC5AC protein and mRNA were lower in the SP600125 group and in the PD98059 group than those in the CSE group (P<0.05). CONCLUSION After being activated by JNK and ERK which are phosphorylated by cigarette smoke, AP-1 binds to its DNA binding elements on the promoter of MUC5AC gene and up-regulates the MUC5AC expression at the transcriptional level.
Bronchi ; cytology ; Cells, Cultured ; Epithelial Cells ; cytology ; metabolism ; Humans ; Mucin 5AC ; genetics ; metabolism ; Smoke ; adverse effects ; Smoking ; adverse effects ; Tobacco ; chemistry ; Transcription Factor AP-1 ; pharmacology

BACKGROUNDIt has been reported that the nicotinic acetylcholine receptor subunit α4 gene (CHRNA4) might be associated with smoking behaviors in the previous studies. Up to now, there are few reports on the relationship between CHRNA4 and smoking initiation. In this study, we tried to explore the role of two polymorphisms in CHRNA4 (rs1044396 and rs1044397) in smoking initiation and nicotine dependence in Chinese male smokers.

METHODSNine hundred and sixty-six Chinese male lifetime nonsmokers and smokers were assessed by the Fagerström test for nicotine dependence (FTND), smoking quantity (SQ) and the heaviness of smoking index (HSI). All subjects were divided into four groups based on their tobacco use history and the FTND scores. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find two polymorphisms of CHRNA4 in these subjects.

RESULTSThe χ(2) test showed that rs1044396 was significantly associated with smoking initiation (χ(2) = 4.65, P = 0.031), while both rs1044396 and rs1044397 were significantly associated with nicotine dependence (χ(2) = 5.42, P = 0.020; χ(2) = 7.58, P = 0.005). Furthermore, the T-G (3.9%) haplotype of rs1044396-rs1044397 showed significant association with smoking initiation (χ(2) = 6.30, P = 0.012) and the C-G haplotype (58.9%) remained positive association with nicotine dependence (χ(2) = 8.64, P = 0.003) after Bonferroni correction. The C-G haplotype also significantly increased the HSI (P = 0.002) and FTND scores (P = 0.001) after Bonferroni correction.

CONCLUSIONThese findings suggest that CHRNA4 may be associated with smoking initiation and the C-G haplotype of rs1044396-rs1044397 might increase the vulnerability to nicotine dependence in Chinese male smokers.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; genetics ; Receptors, Nicotinic ; genetics ; Smoking ; adverse effects

BACKGROUNDEpidermal growth factor receptor (EGFR) mutations in lung carcinomas can make the disease more responsive to the treatment with tyrosine kinase inhibitors. We aimed to evaluate the prevalence of EGFR mutations in a large series of lung carcinomas.

METHODSWe examined 1195 consecutive lung cancer patients for EGFR mutations in exons 18, 19, and 21 using direct sequencing of polymerase chain reaction products. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit > 1 year ago), or current smokers (quit < 1 year ago).

RESULTSThere were EGFR mutations in 9 (4.5%) of 201 squamous carcinomas, in 1 (2%) of 50 large cell carcinomas, and in 1 (2.3%) of 44 small cell carcinomas that were investigated. Three hundred and twenty-seven mutations were found in the series of 858 adenocarcinomas (38.1%). Among 858 lung adenocarcinomas, we detected EGFR mutations in 250 (48.6%) of 514 never smokers, 39 (33.9%) of 115 former smokers, and 38 (16.6%) of 229 current smokers. Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P = 0.0002) or stopped smoking less than 15 years ago (P = 0.033) compared with individuals who never smoked.

CONCLUSIONSAdenocarcinoma is the most frequent EGFR mutation pathologic type in lung cancer. The likelihood of EGFR mutations in exons 18, 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 15 years ago. These data can assist clinicians in assessing the likelihood of exons 18, 19, or 21 EGFR mutations in Chinese patients with lung cancer when mutational analysis is not feasible.

Adenocarcinoma ; genetics ; DNA Mutational Analysis ; Exons ; genetics ; Female ; Humans ; Lung Neoplasms ; genetics ; Male ; Mutation ; Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; genetics ; Smoking ; adverse effects

OBJECTIVETo investigate the risk factors of lung cancer in Tianjin and to provide evidence for further monitor there of.

METHODSA case-control study involving interviews with 193 new cases and 259 controls aged 30 - 76 years was carried out. Structured questionnaires were used to collect information on general condition, living environment, living style, disease and family history, etc. Logistic regression model univariate and multivariate analysis were used to pick out the significant lung cancer risk factors.

RESULTSBy monovariate analysis, risk factors such as smoking, passive smoking, drinking, history of malignancy in family and occupation were found. By multivariate analysis, smoking, passive smoking, higher body mass index (BMI) and average income and living space per capita ten years earlier were ascertained, their operations research (OR) values were 3.302, 1.193, 1.003, 1.067 and 0.913.

CONCLUSIONSmoking and passive smoking are independent risk factors of lung cancer. Monthly income per person and living space per person 10 years earlier are associated with elevated risk of lung cancer. Higher body mass index has protective effects on lung cancer risk.

Adult ; Aged ; Humans ; Logistic Models ; Lung Neoplasms ; etiology ; genetics ; Middle Aged ; Occupations ; Risk Factors ; Smoking ; adverse effects

OBJECTIVETo investigate the influence of cigarette smoking on human sperm DNA integrity.

METHODSTotally, 784 cases of male infertility were selected from our case database and grouped according to whether they were smokers or nonsmokers, how much they smoked (< or = 10, 11-19 and > or = 20 cigarettes/d) and how long they smoked (< or = 5, 6-9 and > or = 10 yr). Sperm DNA integrity was measured using sperm chromatin structure assay (SCSA) and flow cytometry. DNA fragmentation and immature spermatozoa were expressed by the DNA fragmentation index (DFI) and high DNA stainability (HDS) respectively. Conventional sperm parameters and sperm DNA integrity were compared among different groups.

RESULTSThe total semen volume and percentage of grade a + b sperm were lower and the sperm morphological abnormality was higher in the > or = 20 cigarettes/d and > or = 10 yr groups than in the others (P < 0.05). DFI and HDS were significantly higher in the smokers than in the nonsmokers (P < 0.05). HDS was negatively correlated with the percentage of grade a + b sperm (r = -0.18, P < 0.05) and both DFI and HDS were positively correlated with the rate of sperm malformation (r = 0.31 and r = 0.39, P < 0.05).

CONCLUSIONSmoking more than 20 cigarettes a day or longer than 10 years has deleterious effects on the semen volume, percentage of grade a + b sperm and sperm morphology of the smokers. Cigarette smoking decreases sperm DNA integrity and nuclear maturation.

Adult ; DNA Damage ; drug effects ; DNA Fragmentation ; Humans ; Infertility, Male ; genetics ; Male ; Middle Aged ; Smoking ; adverse effects ; Sperm Count ; Sperm Motility ; Spermatozoa ; drug effects ; Young Adult

OBJECTIVETo study the association of genetic polymorphism of glutathione S-transferase M1 (GSTM1) and its susceptibility to esophageal cancer.

METHODSOdds ratio was employed to evaluate the risk of esophageal cancer and GSTM1 status. To take into account the possibility of heterogeneity across the studies, a statistical test for heterogeneity across the studies was performed. Both fixed and random effect Meta-analysis models were used. Publication bias was evaluated by funnel plot.

RESULTSA total of 1190 cases and 1964 controls from 11 studies was included. The pooled OR (with 95% CI) was 1.197 (0.846 - 1.692). Of 11 studies, 5 studies were stratified by smoking. In smoking groups, the pooled OR was 1.523 (1.099 - 2.109) while in non-smoking groups, the pooled OR was 0.933 (0.469 - 1.692).

CONCLUSIONOur results through Meta-analysis did not support the association between GSTM1 null genotype and esophageal cancer, but the smokers carring the GSTM1 null genotype might be associated with the increased risk of esophageal cancer.

Case-Control Studies ; Esophageal Neoplasms ; enzymology ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Glutathione Transferase ; biosynthesis ; genetics ; Humans ; Male ; Odds Ratio ; Polymorphism, Genetic ; Risk Factors ; Smoking ; adverse effects

OBJECTIVETo investigate the relationship between tobacco smoking, drinking and p53 alteration in esophageal carcinoma.

METHODSLiterature on the relationship between p53 alteration in esophageal carcinoma and tobacco smoking, drinking through Meta-analysis were reviewed.

RESULTSIn 14 selected papers related to tobacco smoking, pooled odds ratio (OR) of tobacco smoking with P53 overexpression and p53 alteration were 1.99 (95% CI: 1.30- 3.06) and 1.64 (95% CI: 1.13 - 2.37), respectively (P < 0.05). Pooled OR of tobacco smoking with p53 mutation was 1.11 (95% CI: 0.47 - 2.76) (P > 0.05). In 11 selected papers on alcohol drinking, pooled OR of drinking with P53 overexpression, p53 mutation and p53 alteration were 1.30 (95% CI: 0.83 - 2.04), 1.13 (95% CI: 0.67 - 1.90) and 1.22 (95% CI: 0.87 - 1.72) respectively (P > 0.05).

CONCLUSIONThere were significant relations between tobacco smoking and p53 alteration while there were no significant relations between alcohol drinking and p53 alteration.

Alcohol Drinking ; Esophageal Neoplasms ; etiology ; genetics ; Female ; Genes, p53 ; genetics ; Humans ; Male ; Mutation ; Risk Factors ; Smoking ; adverse effects ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics

OBJECTIVETo explore the risk factors of Parkinson disease (PD), interaction between family history of PD and other risk factors, as well as the relative strength of genetic factors over the vulnerability of PD.

METHODSOne 1:1 matched case-control study including 157 pairs of cases and controls was conducted in Qilu Hospital of Shandong University.

RESULTSConditional logistic regression analysis showed that family history of PD, mental labor, insecticide, alcohol drinking and history of depression all had positive relationship, while smoking had a negative relationship with PD. The AP (AB)s of family history of PD and insecticide, alcohol drinking, history of depression were 55.2%, 34.0%, 41.4% and the RERIs were 8.96, 3.31, 7.85 respectively. The heritability of PD patients' first degree relatives was 36.86% +/- 5.76%, and second degree relatives was 20.66% +/- 6.81%.

CONCLUSIONFamily history of PD had an additive model synergism on PD, coexisting with other risk factors. Genetic factors had a smaller action on PD than environmental factors.

Adult ; Alcohol Drinking ; adverse effects ; Case-Control Studies ; Confidence Intervals ; Family Health ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Parkinson Disease ; etiology ; genetics ; Pedigree ; Pesticides ; adverse effects ; Proportional Hazards Models ; Risk Factors ; Smoking ; adverse effects ; Surveys and Questionnaires

OBJECTIVETo explore the relation between genetic polymorphisms of NQO1, GSTT1 and risks of chronic benzene poisoning (BP).

METHODSA case-control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. Polymerase chain reaction (PCR), denaturing high-performance liquid chromatography(DHPLC) and sequencing were used to detect the single nucleotide polymorphisms(SNPs) of the promoter and complete coding-region of NQO1 gene. Multiple PCR was used to detect GSTT1 genotype.

RESULTSIn smoking population, there was 7.73-fold (95% CI: 1.71-34.97, P = 0.010) of risk in BP subjects carrying NQO1c. 609 T/T genotype, compared with those carrying C/C and C/T. genotype. In drinking population, the individuals carrying the 6th extron of NQO1c. 609 T/T homozygote genotype had a 11.00-fold(95% CI: 1.89-63.83, P = 0.005) risk of BP compared to those with NQO1c. 609 C/T and C/C genotypes.

CONCLUSIONThe subjects carrying NQO1c. 609 T/T genotype and together with the habit of smoking or drinking may be more susceptible to BP.

Benzene ; poisoning ; Case-Control Studies ; Ethanol ; adverse effects ; Genotype ; Glutathione Transferase ; genetics ; Humans ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; Occupational Diseases ; genetics ; Occupational Exposure ; Polymorphism, Single Nucleotide ; Smoking ; adverse effects