Synergistic Effect Of Smoking Research Articles

Synergistic effect of smoking on age-related hearing loss in patients with diabetes

This study investigated the synergistic effects of risk factors on age-related hearing loss (ARHL) using nationwide cross-sectional data of 33,552 individuals from the 2010‒2013 Korea National Health and Nutrition Examination Survey. Patients with ARHL were selected based on their pure-tone audiometry results. Previously reported risk factors for ARHL were analyzed using logistic regression and propensity score-matching, and synergistic effects between risk factors were analyzed using propensity score-matching. Of the 12,570 individuals aged 40–79 years, 2002 (15.9%) met the criteria for ARHL. Male sex, exposure to occupational noise, and diabetes showed a significant relationship with ARHL (p < 0.05) in both the logistic regression and propensity score-matching analyses. Smoking and diabetes showed the strongest significant synergistic effect on ARHL (odds ratio [OR] 1.963, 95% confidence interval [CI] 1.285‒2.998; p = 0.002). In the subgroup analysis based on smoking status, current smokers with diabetes had a significant relationship with ARHL (OR 1.883, CI 1.191‒2.975; p = 0.009), whereas ex-smokers with diabetes did not (OR 1.250; CI 0.880‒1.775; p = 0.246). This implies that current smokers with diabetes may benefit from the cessation of smoking. In conclusion, patients with diabetes should strictly avoid or cease smoking to prevent the progression of ARHL.

Seminal plasma protein networks and enriched functions in varicocele: Effect of smoking.

To verify a possible synergistic effect of smoking and varicocele on the seminal plasma proteome and biological functions, a cross-sectional study was performed in 25 smokers and 24 nonsmokers. Samples were used for conventional semen analysis, functional analysis (DNA fragmentation, acrosome integrity and mitochondrial activity) and proteomics by a shotgun approach. Functional enrichment of biological pathways was performed in differentially expressed proteins. Smokers presented lower ejaculate volume (p=.027), percentage of progressively motile spermatozoa (p=.002), total sperm count (p=.039), morphology (p=.001) and higher percentage of immotile spermatozoa (p=.03), round cell (p=.045) and neutrophil count (p=.009). Smokers also presented lower mitochondrial activity and acrosome integrity and higher DNA fragmentation. We identified and quantified 421 proteins in seminal plasma, of which one was exclusive, 21 were overexpressed and 70 were underexpressed in the seminal plasma of smokers. The proteins neprilysin, beta-defensin 106A and histone H4A were capable of predicting the smoker group. Enriched functions were related to immune function and sperm machinery in testis/epididymis. Based on our findings, we can conclude that cigarette smoking leads to the establishment of inflammatory protein pathways in the testis/epididymis in the presence of varicocele that seems to act in synergy with the toxic components of the cigarette.

Heavy metals assessment in Egyptian smokers with lung cancer

Background Smoking and heavy metals are major risk factors and have an important role in development of lung cancer. Purpose The purpose of this study was to investigate the relationship between development of lung cancer and the synergistic effect of smoking and heavy metals in Egyptian smokers. Patients and methods A total of 41 participants enrolled in this study and were subdivided into three groups: smokers with lung cancer (n=11), nonsmokers with lung cancer (n=15), and apparently healthy smokers (n=15). The diagnosis and types of lung cancer based on pathological examination of biopsies taken either by computed tomography-guided, ultrasound-guided, fiberoptic bronchoscopy (FOB), and blind or thoracoscopic pleural biopsy. Serum levels of five heavy metals (zinc, lead, nickel, manganese, chromium) were assayed using inductive plasma spectrometry. Results Squamous cell carcinoma represents the major type of lung cancer (72.7%) among group of smokers with lung cancer; however, adenocarcinoma either primary or metastatic represents the major type (93.4%) among the nonsmoker group, and all investigated heavy metals in this study (zinc, lead, nickel, manganese, chromium) express significantly higher mean value of their serum levels (P=0.005, 0.005, 0.006, Conclusion Squamous cell carcinoma has been strongly associated with higher serum levels of all investigated heavy metals. There is no association between degree of severity of smoking and serum levels of all investigated heavy metals.

A differentiated approach to the risk assessment from exposure to radon

The paper presents the methods of risk assessment from exposure to radon. Proposed methods implement a differentiated approach to the risk estimates calculation procedure which depends on the purpose of risk assessment. This approach is based on the analysis of the results of practical tests of different risk assessment models on arrays Russian medical and demographic data with and without consideration of the synergistic effect of smoking, in simple and complex exposure scenarios. All of these tests were performed in previous 5 years (results are available elsewhere). In this work the evaluation of effectiveness of radon mitigation actions in schools was used as a test task and results obtained using 4 models («EPA-2003», «Wismut-2006», «FCZ» and «Tomasek-2014») were compared. If it is important to evaluate the effect of reduction of radon concentration on the health of children and adolescents in terms of lifetime lung cancer risk, «Tomasek-2014» model will be the best choice. It is as sensitive as «FCZ» model and ERR is close to that from «Wismut-2006» model, which was earlier proposed by other authors for use with some modifications in Russia. If the data on radon concentration are limited (for example data from radiation-hygienic passports of territories) and constant lifelong exposure scenario is considered, it seems reasonable to apply more simple «Darby-2005» model. Thus, the proposed methods could be used by specialists in various fields in a wide range of tasks, from the risk assessment for the purposes of radiation-hygienic certification and comparative assessment of radiation safety of the population of different regions of Russia on the basis of the generalized statistical data, to the risk assessment in practical works where large amounts of measurement data on the radon concentration and complex exposure scenarios are used.

Synergistic effect of smoking with genetic variants in the AMPKα1 gene on the risk of coronary artery disease in type 2 diabetes

Increasing evidence suggests that adenosine monophosphate-activated protein kinase (AMPK) plays a critical physiological role in the cardiovascular system. The objective of this study was to assess the possible correlation between the genetic variability of the AMPKα1 (PRKAA1) gene and the risk of cardiovascular disease, as well as the interactive effects of the genetic variations and environmental factors, on the risk in Chinese patients with type 2 diabetes. Five haplotype-tagging single nucleotide polymorphisms (SNPs) at the AMPKα1 locus and 404 unrelated Chinese Han subjects with type 2 diabetes were studied; 260 individuals with coronary artery disease and 144 non-coronary artery disease controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism assay. Minor allele C at rs3805489 was protective from coronary artery disease in type 2 diabetic subjects compared with allele A (OR 0.67, 95% CI 0.48-0.92, p = 0.015). There was no significant correlation between the genotypes at five SNPs and the risk of coronary artery disease. In addition, a significant interaction was identified between smoking status and rs3805489 (p = 0.018 for interaction). The smokers with genotype AA at the SNP had a three-fold higher risk of coronary artery disease compared with non-smokers with genotypes AC or CC (OR' 3.02, 95% CI' 1.39-6.57, p' = 0.005, after adjustment for other known coronary artery disease risk factors). The genetic variability at the AMPKα1 locus has synergetic effects with smoking to increase the risk of coronary artery disease in the Chinese Han population with type 2 diabetes.

Lack of Associations between Genetic Polymorphisms in GSTM1, GSTT1 and GSTP1 and Pancreatic Cancer Risk: A Multi-Institutional Case-Control Study in Japan

We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. The study population consisted of 360 patients and 400 control subjects, who were recruited from several medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk. Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 and GSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) for individuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1- present genotypes. No synergistic effects of smoking or GST genotypes were observed. Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study.

EPIDEMIOLOGICAL STUDY ON HEAD AND NECK MALIGNANCIES - A STUDY OF 150 CASES

OBJECTIVE: In the present study we investigate the head and Neck Malignancy cases presenting to the ENT department of our Hospital, and analyze the same to give inputs as to the incidence of head and neck malignancies, the symptoms and stage of presentation, lifestyle and habits as contributory risk factors, identify ENT primary in neck secondaries, histopathological types and selection of best treatment. METHODS: Prospective analysis of 150 patients with newly diagnosed malignancies of nasopharynx, oropharynx, larynx, hypopharynx and ear. RESULTS: Most malignancies are common in patients greater than 40 years of age. 88% of cancer occur in males. Oropharynx cancer is the most common cancer in our study, with the commonest subsite as base of tongue. Supraglottic and pyriform fossa tumours are the commonest tumour in laryngeal and hypopharyngeal cancers respectively. The most common presentation is dysphagia. Synergistic effect of smoking and alcohol is seen in 50% of patients. Most of the cases were seen in stage III and IV except glottis cancer which is predominantly seen in stage I, almost all cases were squamous cell carcinoma. CONCLUSION: The results of our study were in conformity with other similar studies. In larynx, Supraglottic was more common as opposed to glottis in certain western studies. Analysis of various factors helps in early diagnosis and management.

Abstract LB-337: Synergistic effects of twelve common genetic polymorphisms and smoking habits on absolute risk of bladder cancer

Abstract Smoking is the strongest established risk factor for bladder cancer and recent studies have identified multiple common susceptibility loci for this disease. Evaluation of gene-smoking interactions on absolute risk of bladder cancer could be important for understanding both the public health and biological significance of the combined effect of these factors. However, previous studies of gene-environment interactions focused on relative rather than absolute risk measures and thus did not address this important question. The aim of our analyses was to estimate absolute risk of bladder cancer in relation to smoking habits and 12 known susceptibility variants for this disease, and to evaluate if smoking risk differences (RD) vary by levels of a polygenic risk score derived from these variants, using additive tests for interaction. Analyses were based on data from 4,098 cases and 5,995 controls of European background in eight studies participating in the NCI bladder cancer genome-wide association study (GWAS). Absolute risks were estimated based on US incidence and mortality data. The main outcome measures were 30-year cumulative absolute risk of bladder cancer and RDs for males aged 50 years in relation to smoking habits and the polygenic risk score. RDs for ever compared to never smokers were significantly larger (P-additive interaction &amp;lt; 0.05) for subjects carrying risk alleles for seven out of 12 known susceptibility variants. Polymorphisms in two detoxification enzymes, NAT2 and UGT1A6, provided the strongest evidence of additive interactions (P-additive interaction of 0.0002 and 0.0003, respectively), supporting the presence of biological interactions between smoking and these variants. The 30-year risk of bladder cancer in never, former and current smokers was 0.7%, 1.6% and 3.7%, respectively, for subjects in the bottom quartile of the polygenic risk score, compared to 2.0%, 5.1% and 8.0% for subjects in the top quartile. This translates into a significantly larger number of projected cases, which could be avoided by smoking prevention in subjects at higher compared to lower genetic risk (P-additive (2df)=4.6x10-9 for top to bottom quartile of the polygenic risk score). In conclusion, our analyses provide strong evidence for synergistic effects of smoking and known susceptibility loci for bladder cancer on the absolute risk of the disease. This indicates that targeting intense smoking prevention efforts to individuals at elevated genetic risk for bladder cancer could improve the public health impact of such efforts. However, genetic susceptibility for other smoking-related diseases, as well as practical and ethical considerations, would need to be taken into account before any recommendations could be made. (MGC, NR are Co-first authors; N.C. and DTS are Co-last authors) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-337. doi:1538-7445.AM2012-LB-337

Alcohol consumption and lung cancer risk in never smokers: a meta-analysis

BackgroundThe role of alcohol consumption as an independent risk factor for lung cancer is controversial. Since drinking and smoking are strongly associated, residual confounding by smoking may bias the estimation of alcohol consumption and lung cancer risk relation. Therefore, we undertook a meta-analysis to quantitatively assess the association between alcohol and risk of lung cancer in never smokers. MethodsAfter a literature search in Medline, we included all case–control and cohort studies published up to January 2010 that reported an estimate of the association between alcohol intake and lung cancer risk in never smokers. ResultsWe selected 10 articles, including 1913 never smoker lung cancer cases. The random-effects pooled relative risk (RR) for drinkers versus nondrinkers was 1.21 [95% confidence interval (CI) 0.95–1.55]. The same figure was 1.05 (95% CI 0.89–1.23) after the exclusion of one outlier study. At the dose–response analysis, RR for an increase in alcohol intake of 10 g/day was 1.01 (95% CI 0.92–1.10). ConclusionsAlcohol consumption was not associated with lung cancer risk in never smokers. Even if the synergistic effect of smoking and alcohol cannot be ruled out, our results suggest that alcohol does not play an independent role in lung cancer etiology.

Roles of the Genetic Polymorphisms of Alcohol-Metabolizing Enzymes on the Immunology in High-Risk Drinkers

Alcohol metabolism involves several enzymes and the individual genetic variations in the alcohol metabolism are related to the absorption, distribution, and elimination of alcohol and metabolites such as acetaldehyde. Therefore, the genetic variations of alcohol-metabolizing enzymes are responsible for the different toxicity of alcohol in several organs like liver and immunological systems. The purpose of this study was to evaluate if the life styles such as drinking and smoking and the genetic variations of alcohol-metabolizing enzymes (ADH2, ALDH2, CYP2E1, and CAT) were associated with the immunological biomarkers. In this study, 105 high-risk drinkers and 102 low-risk drinkers who were excluded from the immune-related diseases and other critical diseases were enrolled to evaluate the immunological functions. Counts of white blood cells, mononuclear cells, and lymphocyte subpopulations, and liver and immunological function tests were measured. Genotypes of alcohol-metabolizing enzymes were assayed by a real-time PCR and PCR-restriction fragment length polymorphism. Generally, the activity of aspartate aminotransferase (AST) was higher than that of alanine aminotransferase (ALT) in alcoholics; however, the activities of AST and ALT were simultaneously elevated in general hepatitis except for alcohol-induced hepatitis. Thus, the higher ratio of AST/ALT was used to be a marker for the alcohol-induced abnormal liver function. Glutamyltransferase (GGT) is produced by the liver cell microsomes and is a useful laboratory marker as an indicator of early liver cell damage. An increase in GGT concentration has been regarded as a marker of alcohol consumption or liver disease. In addition, the synergistic effects of smoking and drinking on the count of white blood cell (WBC) and mononuclear cells were found to be significant. Furthermore, there were higher OR to become high-risk drinkers in subjects with the combination of ALDH2 (*1/*1) genotype and either genotype of ADH2 or CYP2E1 than the others with other combinations of genotypes. Additionally, there were more abnormal immunological tests in the subjects with higher activity of ADH2 and lower activity of ALDH2. Our results suggested that the habits of drinking, smoking, and betel chewing, and genetic variations of alcohol metabolism were associated with the immunological biomarkers.

Occupational and environmental risks in and around a smelter in northern Sweden. IV. Chromosomal aberrations in workers exposed to lead.

A significantly increased frequency of chromosomal aberrations was found among lead-exposed workers at the Ronnskar smelter in northern Sweden. The frequency of aberrations showed a correlation with lead exposure as measured by the blood levels of lead. Strong individual variations were found. No synergistic effect of smoking was observed. Correlations were found between (chromosome and chromatid) breaks and gaps, which lends further support to the notion that gaps may be useful as indicators of genotoxic agents.

Synergistic effect of smoking and blood pressure on augmentation index in men, but not in women

This study was conducted in healthy Japanese subjects to examine the effects of age and gender on the relationship between the risk factors for cardiovascular disease (CVD) and augmentation index (AI), and the effects of clusters of those risk factors on AI. Radial arterial pressure wave analysis was used to obtain AI in 3675 men and 2919 women. AI was found to be higher in women than in men, and age-related increase in AI showed an attenuated curve in subjects aged >or=50 years. A step-wise multivariate linear regression analysis showed that mean blood pressure and smoking are independent significant variables related to AI in men regardless of age, and in women aged <50 years, but not in women aged >or=50 years. A general linear model univariate linear regression analysis showed that mean blood pressure and smoking had a significant interaction for their relation with AI in men, but not in women. In conclusion, among the risk factors for CVD, smoking and blood pressure were found to be independent factors related to increase in AI. Although age-related attenuation of increase in AI was confirmed in Japanese subjects, these risk factors may act to increase AI even in elderly subjects, at least in part. However, the effects of these factors on AI may differ based on gender, and these factors may act synergistically to increase AI in men. On the contrary, these factors may act independently in young women to increase AI without interaction, whereas only the blood pressure seems to increase AI in elderly women.

An Environmental Risk Assessment of Radon in Lantian Karst Cave of Shaanxi, China

The radiation dose and environmental health risk of radon concentration in the Lantian karst cave of China to guides and visitors were estimated based on the continuous radon concentration monitoring. Distinct seasonal variations were observed in the radon concentration of the air inside the cave. The maximum concentration occurred in the summer, whereas the minimum radon concentration occurred during the winter. The annual average radon concentration in the caves investigated is slightly higher than the upper bound of radon action level for underground space used in China and less than the upper bound of radon action level recommended by the International Commission on Radiation Protection (ICRP) for workplaces. The annual effective dose to tour guides working in two investigated caves varies from 4.1 to 16.5mSv, depending on different equilibrium factors together with different dose conversion factors proposed in the literature. The annual maximum time that a tour guide or other worker can safely be inside the cave is estimated to be 1,250 or 2,246h, depending on whether one bases this on the high or mean radon concentration, with an equilibrium factor of one in both cases. Given the synergistic effects of smoking, tour guides who are smokers should be in the cave only 10–20% of these hours. In all cases, the annual effective doses to visitors are well below the 1mSv maximum suggested dose for a member of the public for 1 year.

Osteonecrosis of the jaw induced by orally administered bisphosphonates: incidence, clinical features, predisposing factors and treatment outcome

Osteonecrosis of the jaw (ONJ) is a well-known devastating side effect of bisphosphonate therapy for cancer. Several ONJ cases of patients using oral bisphosphonates have been reported in the literature. The present study analyzed the clinical features, predisposing factors, and treatment outcome of 11 patients with oral bisphosphonates-related ONJ. Osteonecrosis of the jaw (ONJ) is a well-known side effect of parenteral bisphosphonates therapy. Although ONJ has been reported in patients using oral bisphosphonates, documentation of this entity is sparse. It was hypothesized that the clinical features, predisposing factors, and treatment outcome of this population are different from those of oncologic patients. This retrospective bi-central study involved 98 ONJ patients, 13 of whom were treated with oral bisphosphonates. Two patients were excluded because of previous use of intravenous bisphosphonates. The profiles of 11 patients were analyzed. The mean duration of alendronate use before developing ONJ was 4.1 years. ONJ was triggered by dental surgery in 9 patients and by ill-fitted dentures in 2. Heavy smokers were the most recalcitrant subjects. Among the nine patients with at least 6 months of follow-up, ONJ healed completely in three, partially in four, and not at all in two. ONJ is a rare devastating side effect of oral bisphosphonates associated with patient morbidity and high financial burden. Clinicians must be aware of this entity and inform patients of the risks of dental surgery. The synergistic effect of smoking in the pathogenesis of ONJ should be further investigated.

Oral precancerous disorders associated with areca quid chewing, smoking, and alcohol drinking in southern Taiwan

To investigate the prevalence and the associated risk factors of oral precancerous disorders in southern Taiwan. We conducted a cross-sectional community survey interviewing 1075 adult subjects, 15 years of age and over, gathered from randomly selected 591 households, and spanning five villages in southern Taiwan. The study protocol included a visual oral soft tissue examination and a questionnaire-based interview. The chi-square test was used to test the differences in prevalence of oral precancerous lesions and conditions by different "life styles" relating to current risk habits of current areca quid chewing, smoking, and alcohol drinking. To control for possible confounding, a logistic regression model was used to estimate the Odds Ratios (OR) for leukoplakia and oral submucous fibrosis (OSF). 136 precancerous lesions and conditions were detected among 1075 subjects (12.7%). The analysis of the spectrum of oral precancerous disorders detected, leukoplakia (n = 80), OSF (n = 17) and verrucous lesions (n = 9), demonstrated an association with gender (P < 0.001). There were statistically significant associations among leukoplakia (P < 0.01), OSF (P < 0.0001), and verrucous lesions (P < 0.0001) and the life style of current areca quid chewing, smoking, and alcohol drinking. The synergistic effect of smoking and areca quid chewing habit on leukoplakia and OSF was demonstrated. This study reinforces the association of current areca quid chewing without tobacco, cigarette smoking, and alcohol drinking to leukoplakia, OSF, and verrucous lesions in Taiwan.

Joint effects of smoking, noise exposure and age on hearing loss

Smoking has been shown to have adverse effects on hearing, but it's unclear whether smoking interacts with known causes of hearing loss such as noise exposure and ageing. To examine the hypothesis that smoking, noise and age jointly affect hearing acuity. This cross-sectional study was carried out in 535 male adult workers of a metal processing factory. Pure-tone audiometric tests were utilized to assess hearing loss. Noise exposure assessment was based on a job exposure matrix constructed with industrial hygienist scoring and job titles. Each participant answered questionnaires about socio-demographic, life-style, occupational and health-related data. Analysis of the possible underlying biological model was undertaken assessing departures from additivity using measures of the size of the interaction present. Age and occupational noise exposures were, separately, positively associated with hearing loss. For all the factors combined the estimated effect on hearing loss was higher than the sum of the effects from each isolated variable, especially for smoking and noise among those 20-40 years of age, and for smoking and age among those non-exposed to occupational noise. The synergistic effect of smoking, noise exposure and age on hearing loss, found in this study, is consistent with the biological interaction. Furthermore, it is possible that distinct ototoxic substances in the chemical composition of mainstream smoke may synergistically affect hearing when in combination with noise exposure, which needs to be examined in future studies.

A longitudinal follow-up of pulmonary function and respiratory symptoms in workers exposed to manganese.

The purpose of the investigation was to study the effects on the respiratory system in mine workers with long-term exposure to manganese (Mn) in the workplace. The study included a follow-up of pulmonary function and respiratory symptoms among 145 workers employed in a large Mn mine and 65 matched controls, and the assessment of Mn concentrations in environment and biological samples. Lung function was measured by recording spirometric parameters. The Mn-exposed workers reported more respiratory symptoms and a significantly higher prevalence of all grades of pulmonary function impairment. All predicted symptoms except for asthma increased significantly in the current smoking group compared with the non-smoking group. There was a significant decrease in FEV1, FVC, and FEV1% values in exposed workers compared with controls at stages 2 and 3, with an additive effect of the smoking habit. The Mn concentrations in blood, urine, and hair were significantly higher in the exposed workers than in the controls. The level of cumulative exposure index of workplace Mn was notable and did not change significantly over this study. The respiratory effects found in Mn-exposed workers were probably caused by the Mn in the workplace and the synergistic effect of smoking. These effects indicate a need for respiratory protection and improvements in the work environment.

Chromosome Damage in Lymphocytes of Stainless Steel Welders

Genotoxic effect of welding fumes generated by Manual Metal Arc (MMA), Metal Inert Gas (MIG) and Oxy- acetylene welding on the lymphocytes of 75 welders, 25 from each group and equal number of healthy matched controls, was investigated by studying Mitotic Index (MI), Chromosome Aberrations (CAs), Sister Chromatid Exchanges (SCEs), and Satellite Associations (SAs) The MI showed significant increase in all the three groups (4.25 - 7.66, 4.35 - 7.63, 4.63 - 7.54). The background frequency for CAs was normal (0.88, 0.84, 0.92). It significantly increased in all the three groups (4.68, 3.84, 2.96). Among controls only chromatid gaps and breaks were observed, while chromosome type aberrations could not be seen. Among exposed samples both chromatid type viz. gaps, breaks and isochromatid exchanges and chromosome type ab- errations viz. dicentrics, rings, acentric fragments, transloca- tions, chromosome gaps, chromosome breaks and diplochromosomes were observed. The frequency of SCEs also increased (3.98 - 7.84, 4.16 - 4.72, 4.57 - 6.43). However, the increase was significant in group-1 and group-3 welders only. Synergistic effect of smoking and alcohol was noticed in both CAs and SCEs, the frequencies being the highest in smoker- alcoholics and lowest in non smoker - non alcoholics. The CAs and SCEs also revealed correlation with the duration of expo- sure. The frequencies of SAs also depicted significant increase (4.8 - 13.8, 5.64 - 11.48, 5.56 - 9.28). The D-G type of associa- tions outnumbered all other types. It is concluded that the weld- ing fumes, containing chromium (Cr VI) and nickel, cause con- siderable chromosomal damage. The welders, in their occupa- tional settings are prone to high genetic risk.

Relationships between cigarette smoking, alcohol drinking, the ALDH2 genotype and adenomatous types of colorectal polyps in male self-defense force officials.

Alcohol drinking as well as cigarette smoking has been associated with development of colorectal polyps, Asians such, as Japanese, Chinese and Korean have high frequency of genetic polymorphism in low Km aldehyde dehydrogenase (ALDH2) gene which greatly regulates alcohol intake. In the present study, we investigated associations of this polymorphism and lifestyles with colorectal polyps in self-defense forces personnels in Japan. All subjects received colonoscopy at a retirement health examination. The ALDH2 genotype was determined using polymerase chain reaction and restriction fragment length polymorphism method. Frequency of the ALDH2 genotype was not different between those with colorectal polyps (n=69) and those without the polyps (n=131). Smoking was associated with development of colorectal polyps (OR=4.7, 95% confidence interval=1.9-11.5) in the ALDH2 proficient genotype. The association appeared to be enhanced by drinking alcohol since a synergistic effect of smoking and alcohol drinking (> or =60 ml/day) was indicated (OR=9.9, 95% confidence interval=2.9-34.1) by logistic regression analysis. In the ALDH2 deficient genotype, however, we could not evaluate interactions of smoking and alcohol drinking on colorectal polyp development because of the small sample size of heavy alcohol drinkers. The genotype analysis would be useful in evaluating effects of environmental factors on outcomes for each genetically defined subpopulation.

Monocyte Tissue Factor Expression Is Enhanced in Women who Smoke and Use Oral Contraceptives

The association between use of oral contraceptives (OCs) and increased risk of thromboembolic disease has been firmly established. This risk increases when use of OCs is combined with cigarette smoking. The cellular mechanism favoring an hypercoagulable state under these behaviours is not known. Circulating monocytes are potent activators of the coagulation cascade through their ability to synthesize procoagulant tissue factor (TF). In the present study we report that monocyte TF expression is increased in women who use OCs and smoke. We studied monocyte TF expression in 4 groups of healthy pre-menopausal women (n = 15 each): (1) non-smoking OC non-users, (2) nonsmoking current OC users, (3) smoking OC non-users and (4) smoking OC users. TF expression was assessed on both mRNA and protein levels in unstimulated and LPS-stimulated cells. Transcriptional activation of the TF gene was assessed by analysis of the transcription factor NF-kappaB and its inhibitor molecule IkappaBalpha. Monocyte TF generation was significantly higher in OC users than in women who did not use OCs. Enhanced monocyte TF generation was also observed in smoking women when compared to non-smokers. Strongest monocyte TF expression occurred in women with combined smoking and use of OCs. The enhanced TF expression in monocytes from women using OCs or smoking was based on an increased TF gene transcription following activation of NF-kappaB. Experiments on cultured monocytes/macrophages demonstrated enhanced IkappaBalpha degradation in the presence of estradiol, suggesting that a direct hormone effect is responsible for the observed increase in monocyte TF expression. This study demonstrates that use of OCs and smoking is associated with an increase in monocyte TF expression in pre-menopausal women. Aberrant TF expression by blood monocytes may favour intravascular clotting activation in women with OC therapy. The further enhancement of TF activity observed in women who smoke and use OCs may explain the synergistic effect of smoking on risk of thromboembolic events associated with contraceptive use.