Combination Of Cigarette Smoke Research Articles

Cigarette smoking combined with genetic variation regulates the m6A methylation of CRNKL1 and is associated with bladder cancer risk.

Cigarette smoking was known to accelerate the occurrence and development of bladder cancer by regulating RNA modification. However, the association between the combination of cigarette smoking and RNA modification-related single nucleotide polymorphisms (RNAm-SNPs) and bladder cancer risk remains unclear. In this study, 1681 participants, including 580 cases and 1101 controls, were recruited for genetic association analysis. In total, 1 287 990 RNAm-SNPs involving nine RNA modifications (m6A, m1A, m6Am, 2'-O-Me, m5C, m7G, A-to-I, m5U, and pseudouridine modification) were obtained from the RMVar database. The interactive effect of cigarette smoking and RNAm-SNPs on bladder cancer risk was assessed through joint analysis. The susceptibility analysis revealed that 89 RNAm-SNPs involving m6A, m1A, and A-to-I modifications were associated with bladder cancer risk. Among them, m6A-related rs2273058 in CRNKL1 was associated with bladder cancer risk (odds ratios (OR) = 1.35, padj = 1.78 × 10-4), and CRNKL1 expression was increased in bladder cancer patients (p = 0.035). Cigarette smoking combined with the A allele of rs2273058 increased bladder cancer risk compared with nonsmokers with the G allele of rs2273058 (OR = 2.40, padj = 3.11 × 10-9). Mechanistically, the A allele of rs2273058 endowed CRNKL1 with an additional m6A motif, facilitating recognition by m6A reader IGF2BP1, thereby promoting CRNKL1 expression under cigarette smoking (r = 0.142, p = 0.017). Moreover, elevated CRNKL1 expression may accelerate cell cycle and proliferation, thereby increasing bladder cancer risk. In summary, our study demonstrated that cigarette smoking combined with RNAm-SNPs contributes to bladder cancer risk, which provides a potential target for bladder cancer prevention.

The combination of cigarette smoke and solar rays causes effects similar to skin aging in a bilayer skin model

Skin aging is a multifactorial process influenced by internal and external factors. The contribution of different environmental factors has been well established individually in the last few years. On the one hand, man is rarely exposed to a single factor, and on the other hand, there is very little knowledge about how these extrinsic factors may interact with each other or even how the skin may react to chronic exposure. This study aimed to evaluate the effect on skin aging of a chronic co-exposure of tissue-engineered skin substitutes to cigarette smoke extract (CSE) and solar simulator light (SSL). Skin substitutes were reconstructed according to the self-assembly method and then exposed to CSE followed by irradiation with SSL simultaneously transmitting UVA1, visible light and infrared. When skin substitutes were chronically exposed to CSE and SSL, a significant decrease in procollagen I synthesis and the inhibition of Smad2 phosphorylation of the TGF-β signaling pathway were observed. A 6.7-fold increase in MMP-1 activity was also observed when CSE was combined with SSL, resulting in a decrease in collagen III and collagen IV protein expression. The secretory profile resulting from the toxic synergy was investigated and several alterations were observed, notably an increase in the quantities of pro-inflammatory cytokines. The results also revealed the activation of the ERK1/2 (3.4-fold) and JNK (3.3-fold) pathways. Taken together, the results showed that a synergy between the two environmental factors could provoke premature skin aging.

The Combination of Cigarette Smoking and Alcohol Consumption Synergistically Increases Reactive Carbonyl Species in Human Male Plasma.

Cigarette smoking and alcohol consumption are major risk factors for lifestyle-related diseases. Although it has been reported that the combination of these habits worsens risks, the underlying mechanism remains elusive. Reactive carbonyl species (RCS) cause chemical modifications of biological molecules, leading to alterations in cellular signaling pathways, and total RCS levels have been used as a lipid peroxidation marker linked to lifestyle-related diseases. In this study, at least 41 types of RCS were identified in the lipophilic fraction of plasma samples from 40 subjects using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Higher levels of 10 alkanals, 5 trans-2-alkenals, 1 cis-4-alkenal, and 3 alkadienals were detected in the smoking/drinking group (N = 10) as compared to those with either habit (N = 10 each) or without both habits (N = 10) in the analysis of covariances adjusted for age and BMI. The levels of 3 alkanals, 1 trans-2-alkenal, 1 alkadienal, and 1 4-hydroxy-2-alkenal in the smoking/drinking group were significantly higher than those in the no-smoking/drinking and no-smoking/no-drinking groups. These results strongly indicate that the combination of cigarette smoking and alcohol drinking synergistically increases the level and variety of RCS in the circulating blood, and may further jeopardize cellular function.

Cigarette Smoke Increases CD8α+ Dendritic Cells in an Ovalbumin-Induced Airway Inflammation.

Asthma is an allergic lung disease and, when associated to cigarette smoke exposition, some patients show controversial signs about lung function and other inflammatory mediators. Epidemiologic and experimental studies have shown both increasing and decreasing inflammation in lungs of subjects with asthma and exposed to cigarette smoke. Therefore, in this study, we analyzed how cigarette smoke affects pro-inflammatory and anti-inflammatory mediators in a murine model of allergic pulmonary inflammation. We sensitized Balb/c mice to ovalbumin (OVA) with two intraperitoneal injections. After sensitization, the animals were exposed to cigarette smoke twice a day, 30 min per exposition, for 12 consecutive days. In order to drive the cell to the lungs, four aerosol challenges were performed every 48 h with the same allergen of sensitization. OVA sensitization and challenge developed pulmonary Th2 characteristic response with increased airway responsiveness, remodeling, increased levels of IgE, interleukin (IL)-4, and IL-13. Cigarette smoke, unexpectedly, reduced the levels of IL-4 and IL-13 and simultaneously decreased anti-inflammatory cytokines as IL-10 and transforming growth factor (TGF)-β in sensitized and challenged animals. OVA combined with cigarette smoke exposition decreased the number of eosinophils in bronchoalveolar lavage and increased the number of neutrophils in lung. The combination of cigarette smoke and lung allergy increased recruitment of lymphoid dendritic cells (DCs) into lymph nodes, which may be the leading cause to an increase in number and activation of CD8+ T cells in lungs. In addition, lung allergy and cigarette smoke exposure decreased an important regulatory subtype of DC such as plasmacytoid DC as well as its activation by expression of CD86, PDL2, and ICOSL, and it was sufficient to decrease T regs influx and anti-inflammatory cytokines release such as IL-10 and TGF-β but not enough to diminish the structural changes. In conclusion, we observed, in this model, that OVA sensitization and challenge combined with cigarette smoke exposure leads to mischaracterization of the Th2 response of asthma by decreasing the number of eosinophils, IL-4, and IL-13 and increasing number of neutrophils, which is related to the increased number of CD8ɑ+ DCs and CD8+ T cells as well as reduction of the regulatory cells and its released cytokines.

PTEN/PI3k/AKT Regulates Macrophage Polarization in Emphysematous mice.

Macrophages play an important role in the pathogenesis of COPD. Macrophage polarization towards the M2 phenotype has been observed in the lung tissues of COPD patients and cigarette smokers. The molecular basis of this process remains unclear, and it has not been completely illuminated in animal models of emphysema. In our study, we combined cigarette smoke (CS) exposure with intraperitoneal injection of cigarette smoke extract (CSE) to build an emphysema model. We found by immunohistochemical staining and flow cytometry that the expression level of CD206 and the ratio of M2 to M1 macrophages was increased in emphysematous mice. We also demonstrated that decreased protein level for phosphatase and tensin homology deleted on chromosome ten (PTEN) and increased total protein levels for phosphorylation -protein kinase B (p-AKT) in the lung tissue of emphysematous mice and in CSE-treated RAW264.7 cells. In both bone marrow-derived macrophages (BMDMs) from emphysematous mice and CSE-treated RAW264.7 cells, we observed by RT-PCR that the mRNA levels of M2 macrophage-related markers and cytokines were increased. Furthermore, M1 macrophage-related markers and cytokines were decreased. Meanwhile we treated BMDMs from emphysematous mice and CSE-treated RAW264.7 cells with the phosphoinositide 3-kinase (PI3K)/Akt inhibitor (LY294002), we observed a reduction in RNA levels of M2 macrophage-related markers and cytokines. In conclusion, we confirmed that macrophage M2 polarization was induced in emphysematous mice generated by CS exposure combined with intraperitoneal injection of CSE. We also showed that M2 polarization was mediated through PTEN/PI3k/AKT pathway activation.

Effect of aminophylline and simvastatin on airway inflammation and mucus hypersecretion in rats with chronic obstructive pulmonary disease

To observe the role of aminophylline and simvastatin in preventing and curing chronic obstructive pulmonary disease (COPD), and to explore the underlying mechanisms based on airway inflammation and mucus hypersecretion. The rat model of COPD was established by combination of cigarette smoking with intratracheal lipopolysaccharide (LPS) injection. Male SD rats were randomly divided into 4 groups (n=10 per group): a control group, a COPD group, an aminophylline group and a simvastatin group. The rats in the control group and the COPD group were treated with normal saline once a day via intragastric administration, while the rats in the aminophylline group and the simvastatin group were treated with aminophylline (5 g/L) and simvastatin (0.5 g/L) 1 mL/100 g once a day via intragastric administration, respectively. Pulmonary function and pathological changes in bronchus and lung were observed. The levels of IL-8, IL-17, and TNF-α in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expressions of TLR4 and mucin 5AC (MUC5AC) in bronchi and lung tissues were detected by real-time PCR and Western blot, respectively. Pulmonary function and the pathophysiologic changes in bronchi and lung tissues in the COPD rats were consistent with typical phenotype of COPD. Compared with the control group, lung function indexes were significantly attenuated in the COPD group, while the levels of IL-8, IL-17, and TNF-α in BALF as well as the mRNA and protein levels of MUC5AC and TLR4 were significantly increased. Compared with the COPD group, lung function indexes were significantly increased in the aminophylline group and simvastatin group (P<0.01), while pulmonary pathological damages, the levels of IL-8, IL-17, and TNF-α in BALF as well as the mRNA and protein levels of MUC5AC and TLR4 were significantly decreased (P<0.01). Compared with the aminophylline group, the peak expiratory flow as well as the levels of IL-8, IL-17, and TNF-α in the simvastatin group were elevated (P<0.05). There are no significant difference in the mRNA and protein levels of MUC5AC and TLR4 between the 2 groups (P﹥0.05). Aminophylline and simvastatin can decrease IL-8, IL-17, and TNF-α levels in BALF and inhibit the expression of MUC5AC and TLR4 in airway and lung tissues in COPD rats, suggesting that they may have a preventive and therapeutic effect on COPD through reducing the airway inflammation and mucus hypersecretion.

Brain perfusion in polysubstance users: Relationship to substance and tobacco use, cognition, and self-regulation

BackgroundBrain perfusion is altered in both alcohol dependence and stimulant dependence. Although most substance users also abuse/depend on alcohol concurrently (polysubstance users; PSU), rigorous perfusion research in PSU is limited. Also, the relationships of perfusion abnormalities with cognition, impulsivity, or decision making are not well known. MethodsArterial spin labeling MRI and neuropsychological measures assessed perfusion levels and neurocognition in 20 alcohol-dependent individuals with comorbid-stimulant dependence (PSU), 26 individuals dependent on alcohol only (ALC), and 31 light/non-drinking controls (LD). The patient groups included smokers and non-smokers. ResultsALC had lower perfusion than LD in subcortical and cortical brain regions including the brain reward/executive oversight system (BREOS). Contrary to our hypothesis, regional perfusion was generally not lower in PSU than ALC. However, smoking PSU had lower perfusion than smoking ALC in several regions, including BREOS. Lower BREOS perfusion related to greater drinking severity in smoking substance users and to greater smoking severity in smoking ALC. Lower regional perfusion in ALC and PSU correlated with worse performance in different cognitive domains; smoking status affected perfusion–cognition relationships in ALC only. Lower BREOS perfusion in both substance using groups related to higher impulsivity. ConclusionAlthough regional perfusion was not decreased in PSU as a group, the combination of cigarette smoking and polysubstance use is strongly related to hypoperfusion in important cortical and subcortical regions. As lower perfusion relates to greater smoking severity, worse cognition and higher impulsivity, smoking cessation is warranted for treatment-seeking PSU and ALC.

Combined inhalation of cigarette smoke and coal dust particulate matter 10 increase bone iron level in rats

Objective: This study aimed to elucidate whether inhalation combination of cigarette smoking and particulate matter 10 (PM10) coal dust can change bone mineral elements of rats. Methods: A total of 30 Wistar male rats were randomly divided into three groups including one non-exposure group and two groups of combined cigarette smoke and coal dust. Dose of cigarette smoking was one cigarette per day. Dose of coal dust exposure was 12.5 mg/m3 one hour/day as PM10. Cigarette smoke was exposed prior to coal dust exposure (14 and 28 days). Exposure was done by equipment available in Department of Pharmacology, Faculty of Medicine, University of Brawijaya, Malang, East Java, Indonesia. Bone mineral element was analyzed in femur using X-Ray Fluorescence in Central and Physics Laboratory, State University of Malang, Malang, East Java, Indonesia. ANOVA test was used to analyze the difference levels of bone mineral elements. Results: There are no significant differences for phosphorus, calcium, nickel, copper, zinc and calcium/phosphorus levels in all groups (P > 0.05). Significant increase of iron level in combination cigarette smoke and coal dust exposure was detected when compared with the non-exposure group (P < 0.05). Conclusion: Sub-chronic inhalation combination of cigarette smoke and coal dust PM10 increase bone iron levels in rats.

Cigarette smoke and bleomycin-induced pulmonary oxidative stress in rats

Bleomycin causes pulmonary fibrosis by increasing free oxygen radicals. Cigarette smoke is a strong oxidant which adversely affects pulmonary tissue. We evaluated the effects of cigarette smoke administered with intratracheal bleomycin on pulmonary tissue. We studied 3 groups of rats (n=10): one group received intratracheal saline and served as a control; one received intratracheal bleomycin (IT) (0.5 U/100 g body weight, single dose on the first day), and one group received intratracheal bleomycin (single dose on first day) and tobacco smoke (two times per day) (IT-S). After 4 weeks, the levels of malondialdehyde (MDA) and nitric oxide (NO) and the activities of superoxide dismutase (SOD) and xanthine oxidase (XO) were assayed in the homogenate of the lung tissue samples. The severity of interstitial fibrosis was assessed using the grading system described by Ashcroft. There was more intensive fibrosis in the IT and IT-S than in the control samples (P<0.001). The levels of MDA, NO and activity of XO were significantly increased (P<0.001, <0.002 and <0.002, respectively), and SOD activity (P<0.001) was significantly decreased in the IT group when compared to these values in the control group. The concentration of NO was significantly decreased (P<0.002), and SOD activity was significantly increased (P<0.05) in the lung tissue samples of the IT-S group. Theoretically, the combination of cigarette smoke and bleomycin may have a synergistic effect on oxidative lung injury. In conclusion, we showed that inhalation of cigarette smoke provides protection against oxidative stress in the lung tissue of rats with bleomycin-induced pulmonary fibrosis.

Malondialdehyde–acetaldehyde-adducted protein inhalation causes lung injury

In addition to cigarette smoking, alcohol exposure is also associated with increased lung infections and decreased mucociliary clearance. However, little research has been conducted on the combination effects of alcohol and cigarette smoke on lungs. Previously, we have demonstrated in a mouse model that the combination of cigarette smoke and alcohol exposure results in the formation of a very stable hybrid malondialdehyde–acetaldehyde (MAA)-adducted protein in the lung. In in vitro studies, MAA-adducted protein stimulates bronchial epithelial cell interleukin-8 (IL-8) via the activation of protein kinase C epsilon (PKCɛ). We hypothesized that direct MAA-adducted protein exposure in the lungs would mimic such a combination of smoke and alcohol exposure leading to airway inflammation. To test this hypothesis, C57BL/6J female mice were intranasally instilled with either saline, 30 μL of 50 μg/mL bovine serum albumin (BSA)–MAA, or unadducted BSA for up to 3 weeks. Likewise, human lung surfactant proteins A and D (SPA and SPD) were purified from human pulmonary proteinosis lung lavage fluid and successfully MAA-adducted in vitro. Similar to BSA–MAA, SPD–MAA was instilled into mouse lungs. Lungs were necropsied and assayed for histopathology, PKCɛ activation, and lung lavage chemokines. In control mice instilled with saline, normal lungs had few inflammatory cells. No significant effects were observed in unadducted BSA- or SPD-instilled mice. However, when mice were instilled with BSA–MAA or SPD–MAA for 3 weeks, a significant peribronchiolar localization of inflammatory cells was observed. Both BSA–MAA and SPD–MAA stimulated increased lung lavage neutrophils and caused a significant elevation in the chemokine, keratinocyte chemokine, which is a functional homologue to human IL-8. Likewise, MAA-adducted protein stimulated the activation of airway and lung slice PKCɛ. These data support that the MAA-adducted protein induces a proinflammatory response in the lungs and that the lung surfactant protein is a biologically relevant target for malondialdehyde and acetaldehyde adduction. These data further implicate MAA-adduct formation as a potential mechanism for smoke- and alcohol-induced lung injury.

Interaction in COPD experiment (ICE): A hazardous combination of cigarette smoking and bronchodilation in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease, characterised by poorly reversible, obstructive airflow limitation. Alongside other comorbidities, COPD is associated with increased morbidity and mortality resulting from cardiovascular disease - mainly heart failure and ischemic heart disease. Both diseases share an important risk factor, namely, smoking. About 50% of COPD patients are active cigarette smokers. Bronchodilation is the cornerstone of pharmaceutical treatment for COPD symptoms, and half of all COPD patients use long-acting bronchodilating agents. Discussion about these agents is currently focusing on the association with overall mortality and morbidity in COPD patients, of cardiovascular origin in particular. Bronchodilation diminishes the hyperinflated state of the lung and facilitates the pulmonary deposition of cigarette smoke by deeper inhalation into the smaller airways. Smaller particles, as in smoke, tend to penetrate and depose more in these small airways. In addition, bronchodilation indeed increases carbon monoxide uptake in the lungs, an important gaseous compound of cigarette smoke. Since the number of cigarettes smoked is positively correlated to mortality from cardiac events, we therefore hypothesise that chronic bronchodilation increases cardiovascular disease and mortality in COPD patients who continue smoking by increasing pulmonary retention of pathogenic smoke constituents. Indeed, a recent meta-analysis is suggestive that long-acting anticholinergics might increase cardiovascular disease if patients exceed a certain number of cigarettes smoked. To demonstrate the fundamental mechanism of this pathogenic interaction we will perform a randomised placebo-controlled cross-over trial to investigate the effect of maximum bronchodilation on the retention of cigarette smoke constituents. In 40 moderate to severe COPD patients we measure the inhaled and exhaled amount of tar and nicotine, as well during maximum bronchodilation as during administration of placebo. The fraction of retention of tar and nicotine is subsequently calculated for both circumstances and analysed for association with bronchodilation. Further observational cohort studies or randomised clinical trials designed to monitor cardiovascular events may well evaluate the interaction. Since many patients are at risk for this possibly hazardous interaction, its relevance to our society and healthcare is potentially great. The implication will be that the urgency to quit smoking is intensified. Besides, chronic bronchodilation - specifically long-acting bronchodilators - needs to be discouraged in smoking COPD patients that refuse to quit.

Effects of Cigarette Smoke and Alcohol on Ciliated Tracheal Epithelium and Inflammatory Cell Recruitment

Ciliated epithelium represents the first line of host defense against lung infection. Most alcoholics smoke and are at high risk for developing lung infections. We reported that cigarette smoke activates protein kinase C (PKC) and alcohol desensitizes ciliary beat frequency (CBF) to beta-agonists in bovine bronchial epithelial cells in vitro. The combined effect of smoke and alcohol exposure on mouse ciliated tracheal epithelium has not been studied in vivo. We hypothesized that previously observed in vitro effects of smoke and alcohol exposure could be replicated in vivo. Female C57BL/6 mice were exposed to whole body cigarette smoke only, 20% alcohol ad libitum in drinking water only, or the combination of cigarette smoke plus alcohol for 6 wk. Bronchoalveolar lavage (BAL) cell populations, CBF, and airway kinase activity were assessed. Total BAL cells were decreased in animals exposed to alcohol alone and increased in animals exposed to smoke alone. Mice receiving smoke and alcohol had cell levels similar to smoke alone. Baseline CBF was not affected in any group; however, isoproterenol stimulation of CBF was blunted by alcohol exposure and actually slowed below baseline in the smoke plus alcohol group. Isoproterenol-induced PKA activity was inhibited in mice receiving alcohol independent of smoke exposure. Smoke activated PKC independent of alcohol. The isoproterenol-induced slowing below baseline of CBF after combined smoke and alcohol exposure demonstrates a novel ciliary impairment likely related to the combination of alcohol-mediated PKA desensitization and smoke-stimulated PKC activation, possibly through acetaldehyde present in the vapor phase of cigarette smoke.

The Effect of Modifiable Risk Factors on Pancreatic Cancer Mortality in Populations of the Asia-Pacific Region

Pancreatic cancer accounts for about 220,000 deaths each year. Known risk factors are smoking and type 2 diabetes. It remains to be seen whether these risk factors are equally important in Asia and whether other modifiable risk factors have important associations with pancreatic cancer. An individual participant data analysis of 30 cohort studies was carried out, involving 420,310 Asian participants (33% female) and 99,333 from Australia/New Zealand (45% female). Cox proportional hazard models, stratified by study and sex and adjusted for age, were used to quantify risk factors for death from pancreatic cancer. During 3,558,733 person-years of follow-up, there were 324 deaths from pancreatic cancer (54% Asia and 33% female). Mortality rates (per 100,000 person-years) from pancreatic cancer were 10 for men and 8 for women. The following are age-adjusted hazard ratios (95% confidence interval) for death from pancreatic cancer: for current smoking, 1.61 (1.12-2.32); for diabetes, 1.76 (1.15-2.69); for a 2-cm increase in waist circumference, 1.08 (1.02-1.14). All three relationships remained significant (P < 0.05) after adjustment for other risk factors. There was no evidence of heterogeneity in the strength of these associations between either cohorts from Asia and Australia/New Zealand or between the sexes. In men, the combination of cigarette smoking and diabetes more than doubled the likelihood of pancreatic cancer (2.47; 95% confidence interval, 1.17-5.21) in both regions. Smoking, obesity, and diabetes are important and are potentially modifiable risk factors for pancreatic cancer in populations of the Asia-Pacific region. Activities to prevent them can be expected to lead to a major reduction in the number of deaths from this cancer, particularly in Asia with its enormous population.

The combination of complement deficiency and cigarette smoking as risk factor for cutaneous lupus erythematosus in men; a focus on combined C2/C4 deficiency

Although deficiencies in the early components of the complement system were among the first identified genetic risk factors for systemic lupus erythematosus (SLE), only a few studies addressed their significance in patients with cutaneous LE (CLE). Among environmental factors, it was postulated that cigarette smoking might intervene in the pathogenesis of LE. To describe the clinical and biological features of patients with CLE and a complement deficiency. A secondary objective was to assess cigarette smoking in patients with CLE. A retrospective study including all patients diagnosed as having LE between 1995 and 2003 in the Dermatology Department of Strasbourg University Hospital. Patient charts were reviewed and those patients in whom a C4 and/or C2 deficiency was diagnosed were included. Two patients with a combined C2/C4 deficiency were analysed in detail. There were 48 females and 37 males (F/M ratio = 1.3), with a mean age of 41 years at diagnosis; 73% of the patients had chronic LE and 27% subacute CLE. Among 32 screened patients, 24 patients with a mean age of 36 years had a complement deficiency; 17 had a C4A deficiency, five a C4B deficiency and two a combined C4A/C2 deficiency. A high proportion (58%) of these patients was male; 82% of the patients were smokers. This was especially true in males: 94% were smokers compared with 69% of females. Partial deficiency of C4, C2 or C4 and C2 is a common finding in patients with CLE. Most male patients with CLE are smokers. It is thus suggested that the combination of cigarette smoking and complement deficiency could be a risk factor for LE in men.

Cigarette Smoking and Polymorphism of the Paraoxonase 1 Gene as Risk factors for Lung Cancer

Background : The paraoxonase enzyme plays a significant role in the detoxification of various organophosphorous compounds in mammals, and paraoxonase (PON) 1 is one of the endogenous free-radical scavenging systems in the human body. In this study, we investigated the interaction between cigarette smoking and the genetic polymorphism of PON1 with lung cancer in Korean males. Methods : Three hundred thirty five patients with lung cancer and an equal number of age-matched controls were enrolled in this study. Every subject was asked to complete a questionnaire concerning their smoking habits and alcohol drinking habits. A 5' exonuclease assay (TaqMan) was used to genotype the PON1 Q192R polymorphism. The effects of smoking habits and drinking habits, the PON1 Q192R polymorphism and their interactions were statistically analyzed. Results : Cigarette smoking and the Q/Q genotype of PON1 were significant risk factors for lung cancer. Individuals carrying the Q/Q genotype of PON1 were at a higher risk for lung cancer as compared with those individuals carrying the Q/R or R/R genotype (odds ratio, 2.84; 95% confidence interval, 1.69 - 4.79). When the groups were further stratified by the smoking status, the Q/Q PON1 was associated with lung cancer among the current or ex-smokers (odds ratio, 2.56; 95% confidence interval, 1.52 - 4.31). Current smokers or ex-smokers who had the Q/Q genotype showed an elevated risk for lung cancer (odds ratio: 15.50, 95% confidence interval: 6.76 - 35.54) as compared with the group of subjects who never smoked, and had the Q/R or R/R genotype. The odds ratios (95% confidence interval) of smokers with the PON1 Q/Q type compared to the nonsmokers with the PON1 Q/R or R/R type were 53.77 (6.55 - 441.14) for squamous cell carcinoma, 6.25 (1.38 - 28.32) for adenocarcinoma, and 59.94 (4.66 - 770.39) for small cell carcinoma, and these results were statistically significant. Conclusion : These results suggest that cigarette smoking and the PON1 Q/Q genotype are risk factors for lung cancer. The combination of cigarette smoking and the PON1 Q/Q genotype significantly increased the lung cancer risk irrespective of the histologic type of cancer.

Synergism between smoking and vital exhaustion in the risk of Ischemic stroke: evidence from the ARIC study

To examine the synergism between vital exhaustion and cigarette smoking in producing ischemic stroke. Vital exhaustion (VE), a state characterized by unusual fatigue, irritability, and feelings of demoralization, is measured by the Maastricht questionnaire (MQ), a 21-item inventory of symptoms. The Atherosclerosis Risk in Communities (ARIC) Study is an ongoing cohort study, initiated in 1987. The MQ was administered at the second follow-up visit (1990-1992), and participants were subsequently followed for an average of 6.27 years. Four US communities (Minneapolis, Minnesota; Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi). 13,066 participants aged 48 to 67 years at baseline (Visit 2) with no history of stroke. Validated hospitalized ischemic stroke. During the follow-up period, there were 202 incident ischemic strokes. After multivariate adjustment, current smoking, and high VE were independent risk factors for incident stroke: (smoking vs. non-smoking HR=1.76, p < 0.01; high VE vs. low VE HR=1.94, p < 0.01). For persons with both VE and smoking vs. persons with neither, HR=2.71 (p < 0.001). The proportion of stroke disease burden due to VE and smoking that could be attributed to their interaction was 81 to 93 percent. The combination of cigarette smoking and VE is synergistic in the production of stroke.

Effects of smoking on serum levels of lipid peroxides and essential fat-soluble antioxidants.

The effect of smoking on serum levels of the fat-soluble essential antioxidants (beta-carotene, alpha-tocopherol, gamma-tocopherol, and retinol) and lipid peroxides was studied in 31 smokers and 38 nonsmokers. The study subjects were male student, at King Saud University, aged 18-26 years. Smokers had significantly higher serum levels of lipid peroxides and significantly lower serum concentration of beta-carotene than nonsmokers (P < 0.05). Mean serum concentrations of retinol, alpha-tocopherol, gamma-tocopherol, and total vitamin E were lower among smokers than those of nonsmokers, but the differences were not statistically significant. The lower level of beta-carotene among smokers is probably brought about by the destruction of this antioxidant during neutralization of free radicals present in cigarette smoke. It seems possible that, during such oxidative stress, the interaction among antioxidants and their relative levels in serum are a crucial determinant of the concentration of a particular antioxidant. Therefore, the lower mean levels of alpha-tocopherol and gamma-tocopherol observed in smokers serum may also be related to cigarette smoking. This study has given rise to some concern about the adequacy of dietary beta-carotene, vitamin A and vitamin E of Saudis. The combination of cigarette smoking and low dietary intakes of essential antioxidants may provoke damage by oxidants present in cigarette smoke.

Lifelong exposures and the potential for stroke prevention: the contribution of cigarette smoking, exercise, and body fat.

STUDY OBJECTIVE: To examine the potential for stroke prevention by avoidance of hazards related to lifestyle. Assessment of the lifelong contribution of both individual and combined exposures was a particular...

Coffee consumption and plasma total homocysteine: The Hordaland Homocysteine Study

The health consequences of coffee drinking remain controversial. We report on an association between coffee consumption and the concentration of total homocysteine (tHcy) in plasma, a risk factor for cardiovascular disease and for adverse pregnancy outcome. The study population consisted of 7589 men and 8585 women 40-67 y of age and with no history of hypertension, diabetes, ischemic heart disease, or cerebrovascular disease. They were recruited from Hordaland county of western Norway in 1992-1993. Daily use of coffee was reported by 89.1% of the participants, of whom 94.9% used caffeinated filtered coffee. There was a marked positive dose-response relation between coffee consumption and plasma tHcy, which was stronger than the relation between coffee and total serum cholesterol. In 40-42-y-old men, mean tHcy was 10.1 mumol/L for nonusers and 12.0 mumol/L for drinkers of > or = 9 cups of coffee/d. Corresponding tHcy concentrations in 40-42-y-old women were 8.2 and 10.5 mumol/L, respectively. Although coffee drinking was associated with smoking and lower intake of vitamin supplements and fruit and vegetables, the coffee-tHcy association was only moderately reduced after these variables were adjusted for. The combination of cigarette smoking and high coffee intake was associated with particularly high tHcy concentrations. A strong inverse relation between tea and tHcy concentration in univariate analysis was substantially attenuated after smoking and coffee drinking were adjusted for. The results of the present report should promote future studies on tHcy as a possible mediator of adverse clinical effects related to heavy coffee consumption.

Cancer in relation to occupational exposure to perchloroethylene

Exposure to perchloroethylene (PCE) occurs in a number of occupational settings in which organic solvents are used, and, in particular, is widely prevalent in the dry-cleaning industry. This review summarizes the results of studies of the occurrence of the individual types of cancer in dry cleaners. Two of those cancers of greatest a priori concern (because of results in PCE-exposed experimental animals)--liver cancer and leukemia--have not occurred with increased frequency among persons employed in the dry-cleaning industry. Rates were elevated by about a factor of two for esophageal and bladder cancers, but not increased clearly for any other site. The excess mortality from esophageal cancer was well beyond the limits of chance, based on a total of 23 deaths that occurred in the two principal cohort-studies of dry cleaners. There was some indication of a particularly high risk associated with prolonged employment and a long interval since first employment. However, the possible confounding effect of the combination of cigarette smoking and heavy alcohol consumption, a very strong risk factor for the development of esophageal cancer, could be taken into account only partially in these studies. With regard to bladder cancer, the limited data available suggest that the observed increased risk could be due to exposure to other solvents than PCE used in dry cleaning. The potential influence of occupational exposure to PCE on the occurrence of esophageal and bladder cancer needs continued examination in further follow-up of existing cohorts of dry cleaners, the assembly of additional cohorts, and in large case-control studies that ascertain occupational exposures in some detail.