Joint Effect Of Cigarette Smoking Research Articles

Joint Effects of Cigarette Smoking and Green Tea Consumption with miR-29b and DNMT3B mRNA Expression in the Development of Lung Cancer.

In tumor development, increased expression of DNA methyltransferase (DNMT) has been observed. In particular, cigarette smoke and tea polyphenols may influence DNMT3B mRNA expression by regulating microRNA (miR)-29b expression. Herein, we designed a case–control study to evaluate the joint effects of smoking and green tea consumption, with miR-29b and DNMT3B mRNA expression, in lung cancer development. A total of 132 lung cancer patients and 132 healthy controls were recruited to measure miR-29b and DNMT3B mRNA expression in whole blood. Results revealed that lung cancer patients had lower miR-29b expression (57.2 vs. 81.6; p = 0.02) and higher DNMT3B mRNA expression (37.2 vs. 25.8; p < 0.001) than healthy controls. Compared to non-smokers with both higher miR-29b and lower DNMT3B mRNA expression, smokers with both low miR-29b and higher DNMT3B mRNA expression had an elevated risk of lung cancer development (OR 5.12, 95% CI 2.64–9.91). Interactions of smoking with miR-29b or DNMT3B mRNA expression in lung cancer were significant. Interaction of green tea consumption with miR-29b expression and DNMT3B mRNA expression in lung cancer was also significant. Our study suggests that smokers and green tea nondrinkers with lower miR-29b expression and higher DNMT3B mRNA expression are more susceptible to lung cancer development.

Polymorphisms of TNF-α -308 G/A and IL-8 -251 T/A Genes Associated with Urothelial Carcinoma: A Case-Control Study.

Cigarette smoking and exposure to environmental tobacco smoke are well-known risk factors for urothelial carcinoma (UC). We conducted a hospital-based case-control study involving 287 UC cases and 574 cancer-free controls to investigate the joint effects of cigarette smoking and polymorphisms of inflammatory genes on UC risk. Tumor necrosis factor alpha (TNF-α) -308 G/A and interleukin-8 (IL-8) -251 T/A polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism method. People who had ever smoked and those who were exposed to environmental tobacco smoke had significantly increased UC odds ratios (ORs) of 1.65 and 1.68, respectively. Participants who had smoked more than 18 pack-years had a significantly increased UC OR of 2.64. People who had ever smoked and who carried the A/A genotype of the TNF-α -308 G/A polymorphism had a significantly higher UC OR (10.25) compared to people who had never smoked and who carried the G/G or G/A genotype. In addition, people who had ever smoked and who carried the IL-8 -251 T/T genotype had a significantly increased UC OR (3.08) compared to people who had never smoked and who carried the T/A or A/A genotype. In a combined analysis of three major risk factors (cumulative cigarette smoking, the TNF-α -308 A/A genotype, and the IL-8 -251 T/T genotype), subjects with any one, any two, and all three risk factors experienced significantly increased UC ORs of 1.55, 2.89, and 3.77, respectively, compared to individuals with none of the risk factors. Conclusions. Our results indicate that the combined effects of cumulative cigarette exposure and the TNF-α -308 A/A genotype and/or the IL-8 -251 T/T genotype on UC OR showed a significant dose-response relationship.

Joint Effect of Cigarette Smoking and Body Mass Index on White Blood Cell Count in Korean Adults.

BackgroundWhite blood cell count is an independent risk factor for cardiovascular disease. Several lifestyle and metabolic factors such as cigarette smoking and obesity are known to be associated with an elevated white blood cell count. However, the joint effect of cigarette smoking and obesity on white blood cell count has not yet been fully described.MethodsWe explored the joint effect of cigarette smoking and obesity on white blood cell count using multiple logistic regression analyses after adjusting for confounding variables in a population-based, cross-sectional study of 416,065 Korean adults.ResultsCigarette smoking and body mass index have a dose-response relationship with a higher white blood cell count, but no synergistic interaction is observed between them (men, P for interaction=0.797; women, P for interaction=0.311). Cigarette smoking and body mass index might have an additive combination effect on high white blood cell count. Obese male smokers were 2.36 times more likely and obese female smokers 2.35 times more likely to have a high white blood cell count when compared with normal body mass index non-smokers.ConclusionCigarette smoking and body mass index are independently associated with an elevated white blood cell count in both men and women.

Interactions between cigarette smoking and fine particulate matter in the Risk of Lung Cancer Mortality in Cancer Prevention Study II.

The International Agency for Research on Cancer recently classified outdoor air pollution and airborne particulate matter as carcinogenic to humans. However, there are gaps in the epidemiologic literature, including assessment of possible joint effects of cigarette smoking and fine particulate matter (particulate matter less than or equal to 2.5 µm in diameter) on lung cancer risk. We present estimates of interaction on the additive scale between these risk factors from Cancer Prevention Study II, a large prospective US cohort study of nearly 1.2 million participants recruited in 1982. Estimates of the relative excess risk of lung cancer mortality due to interaction, the attributable proportion due to interaction, and the synergy index were 2.19 (95% confidence interval (CI): -0.10, 4.83), 0.14 (95% CI: 0.00, 0.25), and 1.17 (95% CI: 1.00, 1.37), respectively, using the 25th and 75th percentiles as cutpoints for fine particulate matter. This suggests small increases in lung cancer risk among persons with both exposures beyond what would be expected from the sum of the effects of the individual exposures alone. Although reductions in cigarette smoking will achieve the greatest impact on lung cancer rates, these results suggest that attempted reductions in lung cancer risk through both tobacco control and air quality management may exceed expectations based on reducing exposure to either risk factor alone.

Interactions between Cigarette Smoking and Ambient PM2.5 for Lung Cancer Mortality in the Cancer Prevention Study-II

The International Agency for Research on Cancer recently classified outdoor air pollution and airborne particulate matter as carcinogenic to humans. However, there are gaps in the epidemiologic literature, including assessment of possible joint effects of cigarette smoking and fine particulate matter (PM2.5) on lung cancer risk. We present estimates of interaction on the additive scale between these risk factors from the American Cancer Society Cancer Prevention Study-II a large prospective cohort study of nearly 1.2 million participants recruited in 1982. Estimates of the relative excess risk of lung cancer mortality due to interaction, attributable proportion due to interaction, and synergy index were 2.190 (95% CI -0.103, 4.830), 0.137 (95% CI 0.003, 0.252), and 1.171 (95% CI 1.003, 1.367), respectively, using cutpoints of the 25th and 75th percentile for PM2.5, suggesting small increases in lung cancer risk among those with both exposures beyond what would be expected from the sum of effects of the individual exposures alone. Although reductions in cigarette smoking will achieve the greatest impact on lung cancer rates, results do not rule out that reductions in lung cancer by tobacco control or by air quality management may exceed expectations based on reducing exposure to either risk factor alone.

Single-nucleotide polymorphisms in nucleotide excision repair genes, cigarette smoking, and the risk of head and neck cancer.

Cigarette smoking is associated with increased head and neck cancer (HNC) risk. Tobacco-related carcinogens are known to cause bulky DNA adducts. Nucleotide excision repair (NER) genes encode enzymes that remove adducts and may be independently associated with HNC, as well as modifiers of the association between smoking and HNC. Using population-based case-control data from the Carolina Head and Neck Cancer Epidemiology (CHANCE) Study (1,227 cases and 1,325 controls), race-stratified (White, African American), conventional, and hierarchical logistic regression models were used to estimate ORs with 95% intervals (I) for the independent and joint effects of cigarette smoking and 84 single-nucleotide polymorphisms (SNP) from 15 NER genes on HNC risk. The odds of HNC were elevated among ever cigarette smokers and increased with smoking duration and frequency. Among Whites, rs4150403 on ERCC3 was associated with increased HNC odds (AA+AG vs. GG; OR, 1.28; 95% CI, 1.01-1.61). Among African Americans, rs4253132 on ERCC6 was associated with decreased HNC odds (CC+CT vs. TT; OR, 0.62; 95% CI, 0.45-0.86). Interactions between ever cigarette smoking and three SNPs (rs4253132 on ERCC6, rs2291120 on DDB2, and rs744154 on ERCC4) suggested possible departures from additivity among Whites. We did not find associations between some previously studied NER variants and HNC. We did identify new associations between two SNPs and HNC and three suggestive cigarette-SNP interactions to consider in future studies. We conducted one of the most comprehensive evaluations of NER variants, identifying a few SNPs from biologically plausible candidate genes associated with HNC and possibly interacting with cigarette smoking.

The joint effect of cigarette smoking and polymorphisms on LRP5, LEPR, near MC4R and SH2B1 genes on metabolic syndrome susceptibility in Taiwan

Metabolic syndrome (MetS) is a combination of medical disorders, consisting of multiple, interrelated risk factors of metabolic origin. To investigate the associations of MetS with appetite-related genes (LEPR, near MC4R and SH2B1) and cholesterol metabolism-related gene (LRP5) polymorphism variants and the joint effect of cigarette smoking and these polymorphism variants on MetS in a community-based case-control study. Metabolic syndrome was defined according to the American Heart Association and National Heart Lung Blood Institute (AHA/NHLBI) criteria. A total of 237 MetS cases and 202 subjects without MetS aged 40 or over in Taiwan were analyzed. The genotypes of LRP5-rs3736228, LEPR-rs1137100, near MC4R-rs17782313 and SH2B1-rs4788102 were analyzed by the PCR-restriction fragment length polymorphism method. A strong association of the SNP rs17782313 near MC4R gene with MetS susceptibility was found. The data indicated that the C allele of near MC4R-rs17782313 is an obvious risk factor for MetS susceptibility. The joint effects of cigarette smoking and susceptible genotypes of LRP5, LEPR, near MC4R or SH2B1 genes led to a relatively higher risk of having MetS. Using subjects with the wild-type of LRP5, LEPR, near MC4R or SH2B1 genes and without a smoking habit as a reference group, those with cigarette smoking (current and former) and more than one variant type had a 4.1-fold (95 % CI = 1.6-10.2) risk of having MetS. The genotypes of the appetite-related genes (LEPR, near MC4R and SH2B1) and cholesterol metabolism-related gene (LRP5), together with a cigarette smoking habit, are important risk factors for MetS.

A Case–Referent Study of Lung Cancer and Incense Smoke, Smoking, and Residential Radon in Chinese Men

Background: Burning incense generates large amounts of air pollutants, many of which are confirmed or suspected human lung carcinogens.Objectives: We conducted a population-based case–referent study to examine the effect of incense smoke exposure on lung cancer risk among Chinese males and explored the joint effect of cigarette smoking and exposure to residential radon.Methods: We recruited 1,208 male lung cancer incident cases and 1,069 community referents from 2004 to 2006 and estimated their lifetime exposures to incense smoke and other residential indoor air pollutants based on self-reported information collected during interviews. We performed unconditional multivariable logistic regression analysis to estimate the odds ratio (OR) for lung cancer associated with exposure to incense smoke after adjusting for possible confounders. We conducted stratified analyses by smoking status and exposures to incense burning and residential radon and explored the potential additive-scale interactions.Results: We observed an association between incense exposure and lung cancer that was limited primarily to smokers. Cigarette smoking and high cumulative incense exposure at home appeared to have a synergistic effect on lung cancer (compared with never-smokers who never used incense, the OR for lung cancer for smokers who used incense ≥ 60 day-years = 5.00; 95% confidence interval: 3.34, 7.51). Power was limited, but we also found preliminary evidence suggesting that radon exposure may increase risk among smokers using incense.Conclusion: Our study suggests that exposure to incense smoke in the home may increase the risk of lung cancer among smokers and that exposure to radon may further increase risk.

A significantly joint effect between arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma

Cigarette smoking, arsenic and occupational exposures are well-known risk factors for the development of urothelial carcinoma (UC). Therefore, the aim of this study is to investigate whether the effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures on risk of UC could be modified by genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase omega. A hospital-based case–control study consisted of 520 histologically confirmed UC cases, and 520 age- and gender-matched cancer-free controls were carried out from September 1998 to December 2007. Genotyping of CYP2E1, GSTO1 and GSTO2 was determined by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Subjects with both of cigarette smoking and alcohol consumption have a significantly increased UC risk (odds ratio [OR] = 2.9; 95% confidence interval [CI] = 1.9–4.4). Significantly increased UC risks of 1.5 and 1.9 were found for study subjects with high arsenic exposure and those who have been exposed to two or more occupational exposures, respectively. A significantly increased UC risk of 3.9 was observed in study subjects with H2–H2 diplotype of GSTO1 and GSTO2. The significantly highest UC risk of 9.0 was found for those with all environmental risk factors of cigarette smoking, alcohol consumption, arsenic and occupational exposures and two or more risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2. Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of UC was found.

Cervical and Vulvar Cancer Risk in Relation to the Joint Effects of Cigarette Smoking and Genetic Variation in Interleukin 2

Cigarette smoking is an established cofactor to human papillomavirus (HPV) in the development of cervical and vulvar squamous cell carcinoma (SCC), and may influence risk through an immunosuppressive pathway. Genetic variation in interleukin 2 (IL2), associated in some studies with the inhibition of HPV-targeted immunity, may modify the effect of smoking on the risk of HPV-related anogenital cancers. We conducted a population-based case-only study to measure the departure from a multiplicative joint effect of cigarette smoking and IL2 variation on cervical and vulvar SCC. Genotyping of the four IL2 tagSNPs (rs2069762, rs2069763, rs2069777, and rs2069778) was done in 399 cervical and 486 vulvar SCC cases who had been interviewed regarding their smoking history. Compared with cases carrying the rs2069762 TT genotype, we observed significant departures from multiplicativity for smoking and carriership of the TG or GG genotypes in vulvar SCC risk [interaction odds ratio (IOR), 1.67; 95% confidence interval (CI), 1.16-2.41]. Carriership of one of three diplotypes, together with cigarette smoking, was associated with either a supramultiplicative (TGCT/GGCC; IOR, 2.09; 95% CI, 0.98-4.46) or submultiplicative (TTCC/TGTC; IOR, 0.37; 95% CI, 0.16-0.85 or TGCT/TGCC; IOR, 0.37; 95% CI, 0.15-0.87) joint effect in vulvar cancer risk. For cervical SCC, departure from multiplicativity was observed for smokers homozygous for the rs2069763 variant allele (TT versus GG or GT genotypes; IOR, 1.87; 95% CI, 1.00-3.48), and for carriership of the TTCC/TTCC diplotype (IOR, 2.08; 95% CI, 1.01-4.30). These results suggest that cervical and vulvar SCC risk among cigarette smokers is modified by genetic variation in IL2.

Effect of Breast Cancer Radiotherapy and Cigarette Smoking on Risk of Second Primary Lung Cancer

Prior studies have found that postmastectomy radiotherapy (PMRT) for breast cancer (BC) increases the risk of lung cancer (LC). We explored the joint effects of cigarette smoking and PMRT on LC risk. We conducted a population-based nested case-control study among women registered in the Connecticut Tumor Registry diagnosed with nonmetastatic BC between January 1, 1965 and December 31, 1989. Patient cases developed a LC >or= 10 years after BC diagnosis. Controls were matched to patient cases on age, year of BC diagnosis, and length of survival. Medical records were reviewed for pathology, BC therapy, and smoking history. We used conditional logistic regression to estimate odds ratios for the independent and joint effects of smoking and PMRT on risk of overall, ipsilateral, and contralateral LC. Among 113 second primary LC patient cases and 364 controls, compared with nonsmoking women who did not receive PMRT, nonsmoking women who received PMRT had no higher risk of LC; adjusted odds ratios were 5.9 (95% CI, 2.7 to 12.8) for ever-smokers who did not receive PMRT and 18.9 (95% CI, 7.9 to 45.4) for ever-smokers who received PMRT. Adjusted odds ratios for the joint effects of smoking and PMRT were 10.5 (95% CI, 2.9 to 37.8) for the contralateral lung and 37.6 (95% CI, 10.2 to 139.0) for the ipsilateral lung. Smoking and PMRT were associated with increased risk for all histologic types of LC. PMRT after a diagnosis of BC sharply increased the risk of second primary LC, especially in the ipsilateral lung, among ever-smokers. Clinicians should consider including smoking history in their discussions with patients about the risks and benefits of PMRT.

Joint effect of cigarette smoking and alcohol consumption on mortality

Objective To evaluate the joint effect of cigarette smoking and alcohol consumption on mortality. Methods A population-based cohort of 66,743 Chinese men aged 30–89 in Shanghai, China recruited from 1996 to 2000. Lifestyle data were collected using structured questionnaires. As of November 2004, follow-up for the vital status of 64,515 men was completed and death information was further confirmed through record linkage with the Shanghai Vital Statistics Registry. Associations were evaluated by Cox regression analyses. Results 2514 deaths (982 from cancers, 776 from cardiovascular diseases (CVD)) were identified during 297,396 person-years of follow-up. Compared to never-smokers, both former and current smokers had significantly elevated mortality from any cause, CVD, and cancer; risk increased with amount of smoking. Intake of 1–7 drinks/week was associated with reduced risk of death, particularly CVD death (hazard ratio (HR): 0.7, 95% confidence interval (CI): 0.5, 1.0), whereas intake of > 42 drinks/week was related to increased mortality, particularly cancer-related death (HR: 1.7, 95% CI: 1.1, 2.5). The HR for total mortality associated with moderate alcohol consumption increased from 0.8 (95% CI: 0.6, 1.0) for non-smokers to 1.0 (0.9, 1.2) for moderate smokers and 1.4 (95% CI: 1.2, 1.7) for heavy smokers. Heavy drinkers and heavy smokers had the highest mortality (HR: 1.9, 95% CI: 1.6, 2.4). Conclusions Light and moderate alcohol consumption reduced mortality from CVD. This beneficial effect, however, was offset by cigarette smoking.

The effects of cigarette smoking and alcohol consumption on serum liver enzyme activities: a dose-related study in men.

The separate and joint effects of cigarette smoking and alcohol consumption on serum activities of the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were investigated in 46,775 men attending the BUPA Health Screening Centre in London during the period 1983-1987, after allowing for differences in age, body mass index and exercise level. As expected, all showed a significant positive correlation with alcohol consumption. Cigarette smoking produced a significant increase in GGT activity in all drinking categories bar teetotallers, particularly for those smoking more than 20 cigarettes per day. There were no changes of clinical significance in AST or ALT activities with smoking. We postulate that the combined effects of alcohol and smoking on GGT activity are a result of induction of the enzyme by both alcohol and nicotine. Smoking as well as drinking habits should be taken into account when assessing the significance of an individual's enzyme activities.

The effects of cigarette smoking and alcohol consumption on blood lipids: a dose-related study on men.

The separate and joint effects of cigarette smoking and alcohol consumption on serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides were investigated in 46 750 men attending the BUPA Health Screening Centre in London during the period 1983-1987, after allowing for differences in age, body mass index and exercise level. Drinking alcohol was found to raise both total cholesterol and HDL-C concentrations, in such a way that HDL-C as a percentage of total cholesterol increased with increasing alcohol consumption. LDL-C concentrations increased with increasing alcohol consumption in non-smokers, but decreased in those smoking over 10 cigarettes per day. Drinking had no significant effect on triglycerides except at high levels of consumption. Smoking raised total cholesterol, LDL-C and triglycerides, but lowered HDL-C concentrations. In particular, smoking even small amounts could negate any protective benefit in HDL-C concentrations gained from moderate consumption of alcohol. Assuming a desirable lipid profile to consist of low total cholesterol, LDL-C and triglycerides and a high HDL-C value, this is best achieved for men by being a non-smoking moderate drinker.

Smoking, caffeine, and stress: effects on blood pressure and heart rate in male and female college students.

This study examined the independent and joint effects of cigarette smoking and caffeine consumption on blood pressure (BP) and heart rate (HR) reactions to stress in male and female college students. Following an initial physiological baseline, participants received one of four experimental treatments (paced smoking, caffeine, smoking plus caffeine, or neither) and had BP and HR measured before, during, and after two stressful tasks. The results revealed that, compared with the control condition, caffeine ingestion enhanced the magnitude of stress-induced systolic BP and HR reactions. Smoking combined additively with stress, and the joint effect of smoking and caffeine was no greater than either taken alone. Males and females were generally similar in their BP and HR responses to smoking, caffeine, and stress. Inconsistencies with previous research and possible physiological mechanisms underlying the observed effects are discussed.

The Effects of Maternal Cigarette Smoking on Placental Morphology, Histomorphometry, and Biochemistry

We related cigarette smoking during pregnancy to the macroscopic and microscopic morphology, histomorphometry, and biochemistry of the placenta among participants in The Prenatal Project, a randomized, controlled trial of nutritional supplementation during pregnancy. The aim was to ascertain if the harmful effects of cigarette smoking on the fetus were reflected, and possibly mediated, by changes in the placenta, and whether such changes might be modified by the nutritional supplements, parallel to the nutritional reversal of birthweight depression among heavy smokers. Maternal smoking was associated with increased alkaline ribonuclease (RNase) levels, possibly resulting in disturbed protein synthesis. More smokers had placentas with villous hyperplasia on histologic examination. This was accompanied by biochemical evidence of significantly increased cellularity (increased DNA/gm of placental mass and decreased protein/DNA ratios) and (nonsignificant) trends to reduced syncytial villous cell size on histomorphometry. There were joint effects of cigarette smoking and use of either form of nutritional supplementation on the fibrin and stoma components of the villi, but such changes are not necessarily pathologic. The significant reduction in pathology of the stem villi among smokers was confined to those who were nutritionally supplemented, particularly heavy smokers. This change may thus have reflected the protective effects of supplementation on the birthweight of the offspring of these heavy smokers.