China ; epidemiology ; Humans ; Lung Neoplasms ; epidemiology ; genetics ; Risk ; Smoking

Genome-Wide Association Study ; Humans ; Smoking ; genetics ; Tobacco Use Disorder ; genetics

BACKGROUNDMany studies have suggested that cigarette smoking and polymorphisms of resistin and glutathione peroxidase-1 (GPx-1) genes are closely correlated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, examined the distribution of polymorphisms in GPx-1 and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status.

METHODSNine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter-420C/G and GPx-1 gene Pro198Leu were analyzed by polymorphism-polymerase chain reaction (PCR) in DNA extracted from peripheral blood leukocytes. Interactions between the two mutants and the gene-environment interaction with cigarette smoking were also analyzed.

RESULTSGenotype frequencies of -420C/G (GG) and Pro198Leu (LL) were significantly higher in NAFLD cases (49.56% and 50.11%, respectively) compared with healthy controls (23.67% and 24.22%, respectively) (P = 0.0069; P = 0.0072). Moreover, the risk of NAFLD with -420C/G (GG) was significantly higher than in controls (odds ratio [OR] =3.1685, 95% confidence interval (CI) =1.9366-5.2073). Individuals carrying Pro198Leu (LL) had a high risk of NAFLD (OR = 3.1424, 95% CI = 1.7951-5.2367). Combined analysis of the polymorphisms showed that the -420C/G (GG)/Pro198Leu (LL) genotype was significantly more common in the NAFLD group than in the control group (39.44% vs. 12.78%, respectively, P = 0.0054), while individuals with -420C/G (GG)/Pro198Leu (LL) had a high risk of NAFLD (OR = 5.0357, 95% CI = 3.1852-7.8106). Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in the control group (OR = 1.8990, P = 0.0083 in the smoking index (SI) ≤400 subgroup; OR = 5.0937, P = 0.0051 in the SI >400 subgroup), and statistical analysis suggested a positive interaction between cigarette smoking and -420C/G (GG) (γ = 5.6018 in the SI ≤400 subgroup; γ = 4.4770 in the SI >400 subgroup) and Pro198Leu (LL) (γ = 5.7715 in the SI ≤400 subgroup; γ = 4.5985 in the SI >400 subgroup) in increasing the risk of NAFLD.

CONCLUSIONNAFLD risk factors include -420C/G (GG), Pro198Leu (LL) and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk.

Female ; Genetic Predisposition to Disease ; genetics ; Glutathione Peroxidase ; genetics ; Humans ; Male ; Non-alcoholic Fatty Liver Disease ; metabolism ; Polymorphism, Single Nucleotide ; genetics ; Promoter Regions, Genetic ; genetics ; Resistin ; genetics ; Smoking ; genetics

Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively. The results showed that there was significant difference in genotypes distribution frequency of SP-B1580C/T polymorphism locus between COPD smokers and control smokers. C-->T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9% vs 41.7%, chi2 = 4.93, P<0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1%) of SP-B1580-18A/C locus is lower than T allele (70.9%) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85% and 15% respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race.
Alleles ; China ; ethnology ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; genetics ; Pulmonary Disease, Chronic Obstructive ; genetics ; Pulmonary Surfactant-Associated Protein B ; genetics ; physiology ; Smoking ; genetics

Adenocarcinoma ; genetics ; Adult ; Age Factors ; Aged ; Base Sequence ; Carcinoma, Squamous Cell ; genetics ; DNA, Mitochondrial ; genetics ; Female ; Humans ; Lung Neoplasms ; genetics ; Male ; Middle Aged ; Sequence Deletion ; Smoking ; genetics

Objective: To screen differentially expressed miRNAs in the testis of male rats exposed to cigarette smoke (CS) and identify the early molecular markers of CS-induced apoptosis of testicular cells. METHODS: We randomly divided 200 SPF male SD rats into blank control and low-dose (10 non-filter cigarettes/d), medium-dose (20 non-filter cigarettes/d) and high-dose (30 non-filter cigarettes/d) CS exposure groups. After 2, 4, 6, 8 and 12 weeks of CS exposure, we observed the histopathological changes of the testis by HE staining, detected the apoptosis of the testicular cells by TUNEL, and determined the expressions of caspase-3 and caspase-9 in the testis tissue by immunohistochemistry, RT-PCR and Western blot. Based on the laboratory results, we selected 4 testicular samples from the 12-week high-dose group and another 4 from the control for miRNA microarray-based screening, bioinformatics analysis, and verification of differentially expressed miRNAs in all the animals by RT-PCR. RESULTS: Compared with the controls, the CS-exposed rats showed dose- and time-dependent increase in the atrophy of the testis and significantly increased number of apoptotic testis cells from the 6th week of exposure (P < 0.05), with dramatically up-regulated expressions of caspase-3 (P < 0.01) and caspase-9 protein and mRNA (P < 0.05) in the testis tissue. Microarray-based screening and RT-PCR revealed 5 differentially expressed miRNAs in the testis of the CS-exposed rats, of which miR-138-5p, miR-181d-5p, miR-19a-3p and miR-3588 were down-regulated, and miR-155-5p up-regulated, and the target genes of the differentially expressed miRNAs positively regulated the apoptosis of the testicular cells. CONCLUSIONS The differentially expressed miRNAs miR-155-5p, miR-138-5p, miR-181d-5p, miR-19a-3p and miR-3588 regulate CS-induced apoptosis of testicular cells, and may become biomarkers for early diagnosis and prognosis of CS-induced spermatogenesis obstruction.《.
Animals ; Male ; MicroRNAs/genetics* ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Smoking ; Testis

Pancreatic cancer is an extremely life-threatening neoplasm with a case-fatality rate approaching 100%. Smoking is the major known risk factor for this cancer, explaining 19% of all cases. The nutrition and food consumption patterns play other important roles in the etiology of pancreatic cancer, explaining 35% of all cases. Epidemiological evidences on the relationship between nutrition and pancreatic cancer found consistently positive associations between the intakes of meat, carbohydrates, and dietary cholesterol and pancreatic cancer. Consistent inverse relationships with fruit and vegetable intakes and, in particular, with fiber and vitamin C, have also been noted. Many inherited germline mutations increase the risk of pancreatic cancer. In addition, several common polymorphisms in genes that associated with metabolism of environmental carcinogens, DNA repair and folate metabolism may alter the risk of pancreatic cancer. Interaction between genes and environmental factors may contribute to the risk of pancreatic cancer.
Diet ; Genetic Predisposition to Disease ; genetics ; Humans ; Occupational Exposure ; Pancreatic Neoplasms ; epidemiology ; genetics ; prevention & control ; Polymorphism, Genetic ; Risk Factors ; Smoking

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

Previous studies have suggested that glutathione S-transferase (GST) genotypes may play a role in determining susceptibility to cervical cancer, though the data have often been conflicting. The objective of this study was to examine the effect of GSTP1 polymorphism on cervical carcinogenesis. The studied subjects, patients who were pathologically diagnosed with invasive cervical cancer yielding positive results for human papillomavirus (HPV) (n=342), were compared to healthy, normal, female controls (n=707). DNA from peripheral blood samples from studied subjects whose GSTP1 specific sequences had been determined by PCR with allele-specific primers were reviewed in comparison with the normal controls. The genetic susceptibility of GSTP1 (11q 13.1) in cervical carcinogenesis was determined by examining the effect of gene and environmental factors by the different histopathologic types of invasive cervical cancers. In assessing polymorphism GSTP1, the percentages of individuals homozygous for the A allele, homozygous for the G allele, and heterozygous for the two alleles were 66.8%, 3.9%, and 29.3%, respectively, in the control group, and 64.3%, 4.1%, and 31.6%, respectively, among in women with cervical cancer. Compared with GSTP1 G allele positive (GA or G/G), the odds ratio (OR) (95% confidence interval) for GSTP1 A/A was 1.0 (0.7 - 1.4) for invasive cervical cancer. However, the risk increased with GSTP1 A/A among ever smokers (3.9, 1.7 - 8.9, p-value=0.0012) compared with GSTP1 G allele positive among nonsmokers. In particular, this risk was higher among women with squamous cell carcinoma (4.7, 2.0 - 10.8, p=0.0003). Polymorphism of GSTP1 among smoking women was associated with a higher risk of developing cervical cancer.
Adult ; Aged ; Cervix Neoplasms/*etiology/genetics ; Female ; Glutathione Transferase/*genetics ; Human ; Isoenzymes/*genetics ; Loss of Heterozygosity ; Middle Age ; Polymorphism (Genetics) ; Risk ; Smoking

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