Combined effects of cigarette smoking, DNA methyltransferase 3B genetic polymorphism, and DNA damage on lung cancer.

BACKGROUND: Smoking increases DNA methylation and DNA damage, and DNA damage acts as a vital cause of tumor development. The DNA methyltransferase 3B (DNMT3B) enhances promoter activity and methylation of tumor suppressor genes. Tea polyphenols may inhibit DNMT activity. We designed a case-control study to evaluate the combined effects of smoking, green tea consumption, DNMT3B - 149 polymorphism, and DNA damage on lung cancer occurrence. METHODS: Questionnaires were administered to obtain demographic characteristics, life styles, and family histories of lung cancer from 190 primary lung cancer cases and 380 healthy controls. Genotypes and cellular DNA damage were determined by polymerase chain reaction and comet assay, respectively. RESULTS: The mean DNA tail moment for lung cancer cases was significantly higher than that for healthy controls. Compared to nonsmokers carrying the DNMT3B - 149 CT genotype, smokers carrying the TT genotype had a greater lung cancer risk (odds ratio [OR]: 2.83, 95% confidence interval [CI]: 1.62-4.93). DNA damage levels were divided by the tertile of the healthy controls' values. Compared to nonsmokers with low DNA damage, smokers with moderate DNA damage (OR: 2.37, 95% CI: 1.54-3.63) and smokers with high DNA damage (OR: 3.97, 95% CI: 2.63-5.98) had elevated lung cancer risks. Interaction between smoking and DNA damage significantly affected lung cancer risk. CONCLUSIONS: Our study suggested that the DNMT3B - 149 TT genotype, which has higher promoter activity, can increase the lung cancer risk elicited by smoking, and DNA damage may further promote smoking related lung cancer development.

Clinical Validation of the Preterm Oral Feeding Readiness Assessment Scale in Taiwan.

PURPOSE: A successful transition from gavage to full oral feeding is a decisive indicator for discharging premature infants from the neonatal intensive care unit. A clinically useful measure of oral feeding readiness would help nurses initiate implementation of the cue-based feeding model in Taiwan. The study aimed to assess the validity and reliability of the Traditional Chinese Preterm Oral Feeding Readiness Assessment Scale (TC-POFRAS). DESIGN AND METHODS: 81 preterm infants were enrolled and assessed by TC-POFRAS regarding their oral feeding readiness. This study included two phases. Phase 1 conducted a cross language validation procedure and item-level content validity indices (I-CVIs) for content validity were estimated. In phase 2, Cronbach's alpha for internal consistency at each category and total scale levels were estimated. A receiver operating characteristic (ROC) curve was estimated to explore the scale's performance. The optimal cut-off value of TC-POFRAS was identified by the best Youden's Index [maximum (sensitivity + specificity - 1)]. RESULTS: All of the I-CVIs were 1.00. The whole Cronbach's alpha for internal consistency was 0.804 (95% CI = 0.736-0.862), and Cronbach's alpha values were between 0.538 (95% = 0.332-0.689) and 0.687 (95%CI = 0.572-0.781) for categories. The area under ROC was 92.2%, and an optimal cut-off value of TC-POFRAS was 29 (sensitivity: 0.938, specificity: 0.941). CONCLUSIONS: The TC-POFRAS has been verified to be an effective and accurate instrument to determine the initiation of oral feeding in preterm infants. PRACTICE IMPLICATIONS: The TC-POFRAS is an appropriate and complementary assessment instrument for professionals to conveniently use in clinical practice.

Chronic kidney disease and diabetes associated with long-term outcomes in patients receiving percutaneous coronary intervention.

BACKGROUND: The effect of diabetes mellitus (DM) and chronic kidney disease (CKD) on long-term outcomes in patients receiving percutaneous coronary intervention (PCI) is unclear. METHODS: A total of 1394 patients who underwent PCI were prospectively enrolled and divided into 4 groups according to the presence or absence of DM or CKD. Baseline characteristics, risk factors, medications, and angiographic findings were compared. Determinants of long-term outcomes in patients undergoing PCI were analyzed. RESULTS: Patients with DM and CKD had the highest all-cause mortality and cardiovascular mortality (both P < 0.01) but there were no differences existed in myocardial infarction (MI) or repeated PCI among the 4 groups (P = 0.19, P = 0.87, respectively). Patients with DM and CKD had the lowest even-free rate of all-cause mortality, cardiovascular mortality, MI, and repeated PCI (P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively). In the Cox proportional hazard model, patients with both DM and CKD had the highest risk of all-cause mortality (HR: 3.25, 95% CI: 1.85-5.59), cardiovascular mortality (HR: 3.58, 95% CI: 1.97-6.49), MI (HR: 2.43, 95% CI: 1.23-4.08), and repeated PCI (HR: 1.79, 95% CI: 1.33-2.41). Patients with CKD alone had the second highest risk of all-cause mortality (HR: 2.04, 95% CI: 1.15-3.63), cardiovascular mortality (HR: 2.13, 95% CI: 1.13-4.01), and repeated PCI (HR: 1.47, 95% CI: 1.09-1.97). CONCLUSIONS: DM and CKD had additive effect on adverse long-term outcomes in patients receiving PCI; CKD was a more significant adverse predictor than DM.

The growth and uptake of Ga and In of rice (Oryza sative L.) seedlings as affected by Ga and In concentrations in hydroponic cultures.

Limited information is available on the effects of gallium (Ga) and indium (In) on the growth of paddy rice. The Ga and In are emerging contaminants and widely used in high-tech industries nowadays. Understanding the toxicity and accumulation of Ga and In by rice plants is important for reducing the effect on rice production and exposure risk to human by rice consumption. Therefore, this study investigates the effect of Ga and In on the growth of rice seedlings and examines the accumulation and distribution of those elements in plant tissues. Hydroponic cultures were conducted in phytotron glasshouse with controlled temperature and relative humidity conditions, and the rice seedlings were treated with different levels of Ga and In in the nutrient solutions. The growth index and the concentrations of Ga and In in roots and shoots of rice seedlings were measured after harvesting. A significant increase in growth index with increasing Ga concentrations in culture solutions (<10mgGaL-1) was observed. In addition, the uptake of N, K, Mg, Ca, Mn by rice plants was also enhanced by Ga. However, the growth inhibition were observed while the In concentrations higher than 0.08mgL-1, and the nutrients accumulated in rice plants were also significant decreased after In treatments. Based on the dose-response curve, we observed that the EC10 (effective concentration resulting in 10% growth inhibition) value for In treatment was 0.17mgL-1. The results of plant analysis indicated that the roots were the dominant sink of Ga and In in rice seedlings, and it was also found that the capability of translocation of Ga from roots to shoots were higher than In. In addition, it was also found that the PT10 (threshold concentration of phytotoxicity resulting in 10% growth retardation) values based on shoot height and total biomass for In were 15.4 and 10.6µgplant-1, respectively. The beneficial effects on the plant growth of rice seedlings were found by the addition of Ga in culture solutions. In contrast, the In treatments led to growth inhibition of rice seedlings. There were differences in the phytotoxicity, uptake, and translocation of the two emerging contaminants in rice seedlings.

Correlation Between Smoking Paradox and Heart Rhythm Outcomes in Patients With Coronary Artery Disease Receiving Percutaneous Coronary Intervention.

BACKGROUND: The effect of smoking on short-term outcomes among patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) is controversial. However, little is known about the impact of smoking on long-term outcomes in patients with stable coronary artery disease (CAD) who receive PCI. METHODS: A total of 2,044 patients with stable CAD undergoing PCI were evaluated. They were divided into two groups according to smoking status (current smokers vs. non-smokers). Baseline characteristics, exposed risk factors, angiographic findings, and interventional strategies were assessed to compare the long-term clinical outcomes between groups. Predictors for myocardial infarction (MI), all-cause death, cardiovascular (CV) death, and repeated PCI procedures were also analyzed. RESULTS: Compared with non-smokers, current smokers were younger and mostly male (both P < 0.01). They also had a lower prevalence of chronic kidney disease (CKD) and diabetes (both P < 0.01). Drugs including a P2Y12 receptor inhibitor of platelets (P2Y12 inhibitor), beta-blockers (BB), and statins were used more frequently in current smokers (P < 0.01, P < 0.01, P = 0.04, respectively). Freedom from all-cause death and CV death was lower in the non-smoker group (P < 0.001, P = 0.003, respectively). After adjustment, logistic regression revealed smoking was a major predictor for all-cause death and repeated PCI procedure [hazard ratio(HR): 1.71 and 1.46, respectively]. CONCLUSIONS: Smoker's paradox extends to long-term outcome in patients with stable CAD undergoing PCI, which is partially explained by differences in baseline characteristics. However, smoking strongly predicted all-cause mortality and repeated PCI procedures in patients with stable CAD undergoing PCI.

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.

Promotion of Smoking Cessation Using the Transtheoretical Model: Short-Term and Long-Term Effectiveness for Workers in Coastal Central Taiwan.

Background: Smoking cessation reduces the risk of severe illnesses in the long run and contributes to improving health. This study evaluated the short-term and long-term effectiveness of workplace smoking cessation intervention implemented using the transtheoretical model. Methods: Participants were assessed at baseline before the intervention and after 6 months and 4 years of follow-ups. Data on changes in participants' perception of smoking prohibition in the workplace, knowledge of the hazards of smoking, attitude towards quitting smoking, and behavior related to tobacco harm prevention were collected. Results: Results showed the prevalence of smoking cessation was 31.5% (95% CI: 25.4-38.1%) after 6 months and 10.7% (95% CI: 6.9-15.6%) after 4 years. At the abovementioned time points, the prevalence of second-hand smoke exposure, and the proportion of people who demonstrated correct knowledge of smoke hazards initially decreased and then increased. The proportion of participants who had seen or received information about tobacco harm prevention provided in the workplace increased from 75.6% at baseline to 95.6% (increased by 20.0%) after 6 months and finally to 97.2% (increased by 21.6%) after 4 years (P < .001). However, the percentage of participants who hoped their workplace continued to provide smoking cessation services rose from 80.0% at baseline to 93.6% (increased by 13.6%) after 6 months and then fell to 78.0% (decreased by 2.0%) after 4 years (P < .001). Conclusion: The short-term effectiveness of the transtheoretical model in promoting workplace smoking cessation is substantial, but in the long-term, effectiveness weakens.

Interaction of Adiponectin Genotypes and Insulin Resistance on the Occurrence of Taiwanese Metabolic Syndrome.

BACKGROUNDS: Adiponectin (apM1) may affect insulin sensitivity, and tumor necrosis factor (TNF-α) can inhibit the binding of insulin and insulin receptors. However, whether apM1 and TNF-α genes influence the development of metabolic syndrome (MetS) preceded by insulin resistance is unclear. The current study examines the interactions between the apM1 +45 genotypes, TNF-α -308 genotypes, and insulin resistance on the occurrence of MetS. METHODS: A total of 329 community residents were recruited, and their personal characteristics were collected. Waist circumference and biochemical markers were examined for determining MetS. Genotypes were identified by the polymerase chain reaction. RESULTS: After adjusting for the confounding effects, compared to apM1 +45 GG and GT genotypes carriers with HOMR-IR less than 2.0, those carriers with HOMA-IR greater than 2.0 had an increased MetS risk (OR = 4.35, 95% CI 2.14-8.85). Further, apM1 +45 TT carriers with HOMA-IR greater than 2.0 experienced a higher MetS risk (OR = 5.91, 95% CI 2.78-12.54). A significant interaction of the apM1 +45 genotype and insulin resistance on the MetS development was observed (P = 0.04). CONCLUSION: Our data suggested that apM1 +45 genotypes might modify the effect of insulin resistance on the development of Taiwanese MetS.

ERα determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions.

Mutant p53 (mutp53) commonly loses its DNA binding affinity to p53 response elements (p53REs) and fails to induce apoptosis fully. However, the p53 mutation does not predict chemoresistance in all subtypes of breast cancers, and the critical determinants remain to be identified. In this study, mutp53 was found to mediate chemotherapy-induced long intergenic noncoding RNA-p21 (lincRNA-p21) expression by targeting the G-quadruplex structure rather than the p53RE on its promoter to promote chemosensitivity. However, estrogen receptor alpha (ERα) suppressed mutp53-mediated lincRNA-p21 expression by hijacking mutp53 to upregulate damaged DNA binding protein 2 (DDB2) transcription for subsequent DNA repair and chemoresistance. Levels of lincRNA-p21 positively correlated with the clinical responses of breast cancer patients to neoadjuvant chemotherapy and had an inverse correlation with the ER status and DDB2 level. In contrast, the carboplatin-induced DDB2 expression was higher in ER-positive breast tumor tissues. These results demonstrated that ER status determines the oncogenic function of mutp53 in chemoresistance by switching its target gene preference from lincRNA-p21 to DDB2 and suggest that induction of lincRNA-p21 and targeting DDB2 would be effective strategies to increase the chemosensitivity of mutp53 breast cancer patients.

Accumulation of gallium (Ga) and indium (In) in rice grains in Ga- and In-contaminated paddy soils.

To understand the risk of two emerging contaminants, gallium (Ga) and indium (In) to humans via rice consumption, effects of soil properties and concentrations of spiked Ga/In on the accumulation of Ga and In in rice grains were investigated. A pot experiment was conducted, and paddy rice was grown in three soils with different pH values and Al availabilities (i.e., Pc, TWz and Cf), which were spiked with various Ga and In concentrations. The growth index and concentrations of Ga, In, and Al in plant tissues and soil pore water were measured. Results revealed that the concentrations of Ga and In in soil pore water increase with the spiking of Ga or In in all of the tested soils, but the biomass of roots and shoots does not significantly decrease. The accumulation of Ga in shoots and brown rice was significantly reduced in high available Al acidic soils (Pc soils), but this accumulation was significantly increased in low available Al acidic soils (TWz soils), which can be explained by the competitive uptake between Ga and Al by rice plants. The extent of competitive effects between In and Al was less than that between Ga and Al because of the lower solubility and translocation capability of In than those of Ga in soil-rice systems. However, significant differences in the concentrations of Ga and In in brown rice in neutral soils (Cf soils) among the Ga or In treatment were not observed. In addition, the iron plaque formed on the root surface can serve as a barrier to reduce the accumulation of Ga in rice plants. This study suggested that the risk of accumulation of Ga and In in rice grains should be of concern when paddy rice is grown in acidic Ga- or In-contaminated soils with low Al availability.

Influence of hypercholesterolemia and diabetes on long-term outcome in patients with stable coronary artery disease receiving percutaneous coronary intervention.

Coronary artery disease (CAD) is a life-threatening medical emergency which needs urgent medical attention. Percutaneous coronary intervention (PCI) is common and necessary for patients with CAD. The effect of hypercholesterolemia and diabetes on long-term outcomes in patients with stable CAD receiving PCI is unclear.In this study, patients with stable CAD who underwent PCI were prospectively divided into 4 groups according to the presence or absence of diabetes or hypercholesterolemia. Clinical characteristics, risk factors, medications, angiographic findings, and outcome predictors were analyzed and long-term outcomes compared between groups.Of the 1676 patients studied, those with hypercholesterolemia and diabetes had the highest all-cause mortality rate after PCI (P < .01); those with diabetes only had the highest cardiovascular (CV) mortality (P < .01). However, the 4 groups did not differ in rates of myocardial infarction (MI) or repeated PCI. In Kaplan-Meier survival analysis, patients with diabetes only had the highest rates of all-cause mortality and CV mortality (both P < .001). In the Cox proportional hazard model, patients with both hypercholesterolemia and diabetes had the highest risk of all-cause mortality (hazard ratio: 1.70), but groups did not differ in rates of MI, CV mortality, and repeated PCI.With or without hypercholesterolemia, diabetes adversely impacts long-term outcomes in patients receiving PCI. Diabetes mellitus seemed to be a more hazardous outcome predictor than hypercholesterolemia. Hypercholesterolemia and diabetes seemed to have an additive effect on all-cause mortality in patients after receiving PCI.

Genetic polymorphism of catechol-O-methyltransferase modulates the association of green tea consumption and lung cancer.

Tea polyphenols are strong antioxidants, which can be rapidly O-methylated by catechol-O-methyltransferase (COMT). Thus, it is possible that the genetic polymorphism of COMT can modulate the association of green tea consumption and lung cancer. Here, we designed a case-control study to evaluate the combined effect of green tea consumption and COMT genotypes on the risk of lung cancer. A total of 237 lung cancer patients and 474 healthy controls were recruited. Questionnaires were administered to obtain demographic data, smoking status, green tea consumption, fruits and vegetables intake, exposure to cooking fumes, and family history of lung cancer. Genotypes for COMT were identified by PCR. Smoking, green tea consumption, exposure to cooking fumes, and family history of lung cancer were associated with the development of lung cancer. When green tea drinkers carrying COMT HL/LL genotypes were selected as the reference group, drinkers carrying the COMT HH genotype had a higher risk for the development of lung cancer (odds ratio: 1.97, 95% confidence interval: 0.99-3.91). Among the current and ever smokers, the elevated risk for lung cancer was more apparent in green tea drinkers carrying the COMT HH genotype compared with green tea drinkers carrying COMT HL/LL genotypes (odds ratio: 5.84, 95% confidence interval: 1.75-19.45). Green tea drinkers with greater activity of the COMT genotype, whereby polyphenols are effectively excluded, will gain fewer protective benefits against lung cancer development.

Preparation of rutile and anatase phases titanium oxide film by RF sputtering.

Titanium oxide films were prepared by RF magnetron sputtering onto glass substrates. The effects of RF power and deposition temperature on crystalline structure, morphology and energy gap were investigated, which were analyzed by X-ray diffraction, SEM and UV-Vis spectrometer, respectively. Results show that rutile phase is the favored structure during deposition. Applying RF power in the range of 50-250 W, the amorphous, rutile, and both rutile and anatase phases TiO2 films were obtained in sequence, while the content of anatase is similar in the range of 34-37% although the RF power increases. Increasing the deposition temperature, the anatase phase coexists in the rutile phase in the range of 100-200 degrees C, and the content of anatase increases from 20 to 41% with the deposition temperature. In addition, according to the morphology observation, the granulous surface is found in rutile phase while facetted surface in anatase phase when titanium oxide films deposited at various RF powers and substrate temperatures. The band gap energy of titanium oxide evaluated from (alphahv)1/2 versus energy plots show that the energy gap decreases with RF power increasing.

Hypertension and chronic kidney disease affect long-term outcomes in patients with stable coronary artery disease receiving percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) is commonly used for patients with coronary artery disease (CAD). However, the effects of chronic kidney disease (CKD) and hypertension (HT) on long-term outcomes in patients with stable CAD receiving PCI are still unclear. A total of 1,676 patients treated with PCI were prospectively enrolled and divided into 4 groups according to the presence or absence of HT or CKD. General characteristics, clinical medications, risk factors, angiographic findings, and long-term outcomes were analyzed. Patients with CKD had the highest rate of all-cause and cardiovascular (CV) mortality (both P < 0.01). Patients with CKD alone had the lowest event-free rate of all-cause and CV deaths (both P < 0.001). Based on Cox proportional hazard model, patients with CKD alone had the highest risk of all-cause death (HR:2.86, 95% CI:1.73-4.75) and CV death (HR: 3.57,95% CI:2.01-6.33); while patients with both CKD and HT had the highest risk of repeat PCI (HR: 1.42, 95% CI:1.09-1.85).We found that in stable CAD patients after undergoing PCI, those with CKD alone had the highest long-term mortality. Comorbid CKD appears to increase risk in patient with HT, whereas comorbid HT doesn't seem to increase risk in patients with CKD.

The DNA Methyltransferase 3B -149 Genetic Polymorphism Modulates Lung Cancer Risk from Smoking

Background: Smoking can cause increase of DNA methylation and hypermethylation of tumor suppressor genes, this possible contributing to subsequent lung cancer development. DNA methyltransferase 3B (DNMT3B) is crucial in regulation of DNA methylation and it has been proposed that green tea might lower cancer risk through inhibiting its activity. Here, we designed a case-control study to investigate whether the DNMT3B -149 genetic polymorphism could modulate lung cancer risk due to smoking. Possible interactions of smoking and green tea consumption with this DNMT3B genetic polymorphism were also assessed. Materials and Methods: A total of 190 lung cancer patients and 380 healthy controls were recruited. Questionnaires were administered to obtain data on sociodemographic and lifestyle variables, as well as family history of lung cancer. Genotypes for DNMT3B -149 were identified by polymerase chain reaction. Results: Smoking, green tea consumption, exposure to cooking fumes, family history of lung cancer, and the DNMT3B -149 genotype (odds ratio (OR)=2.65; 95% confidence interval (CI) 1.15-6.10) were all significantly associated with the development of lung cancer. Smokers carrying the DNMT3B -149 TT genotype were at elevated risk compared to non-smokers carrying DNMT3B -149 (OR=7.69; 95% CI 2.55-23.14). Interaction of smoking with DNMT3B -149 genotypes was significant regarding lung cancer risk. However, interaction between green tea drinking and DNMT3B -149 genotypes was not. Conclusions: The DNMT3B -149 TT genotype might increase the smokingassociated lung cancer risk.

Methylphenidate on Cognitive Improvement in Patients with Traumatic Brain Injury: A Meta-Analysis.

Although methylphenidate has been used as a neurostimulant to treat patients with attention deficit hyperactivity disorder, its therapeutic role in the psychomotor or cognitive recovery of patients with traumatic brain injuries (TBIs) in both intensive care and rehabilitation settings has not been adequately explored. To address this issue, this meta-analysis searched the available electronic databases using the key words "methylphenidate", "brain injuries", "head injuries", and "traumatic brain injury". Analysis of the ten double-blind RCTs demonstrated significant benefit in using methylphenidate for enhancing vigilance-associated attention (i.e., selective, sustained, and divided attention) in patients with TBIs (standardized mean difference: 0.45, 95% CI: 0.10 to 0.79), especially in sustained attention (standardized mean difference: 0.66, 95% CI: 0.22 to 1.10). However, no significant positive impact was noted on the facilitation of memory or processing speed. More studies on the efficacy and safety of methylphenidate for the cognitive improvement of patients with TBIs are warranted.

Arsenic accumulation and speciation in rice grains influenced by arsenic phytotoxicity and rice genotypes grown in arsenic-elevated paddy soils.

Rice consumption is a major route of As exposure to human for the population of worldwide. This study investigates the effect of phytotoxicity and rice genotypes on the content and speciation of As in rice grains grown in different levels of As-elevated paddy soils from Taiwan. Three levels of As-elevated soils and six rice genotypes commonly planted in Taiwan were used for this study. The results indicate that As contents in grains of rice is not proportional to soil As concentrations and they were equal or higher in indica genotypes than japonica genotypes used in this study. It was also found that the As phytotoxicity not only reducing the grain yields but also the As concentrations in grain of rice. The predominant As species found in rice grains were dimethylarsinic acid (DMA) and arsenite. The concentrations of DMA increased with total As concentrations, wherggeas the arsenite remained in a narrow range from 0.1 to 0.3 mg kg(-1). Because of the lower toxicity of DMA than inorganic As species, the health risks may not be increased through consumption of rice even when total As content in the grains is increased.

Multidrug resistance 1 gene variants, pesticide exposure, and increased risk of DNA damage.

The P-glycoprotein, encoded by the multidrug resistance (MDR)1 gene, extrudes fat-soluble compounds to the extracellular environment. However, the DNA damage of pesticides in subjects with genetic variation in MDR1 has not been investigated. In this study, the comet assay was applied to examine the extent of DNA damage in the peripheral blood of 195 fruit growers who had been exposed to pesticides and 141 unexposed controls. The MDR1 polymorphisms were identified. Questionnaires were administered to obtain demographic data and occupational history. Results showed subjects experiencing high (2.14 µm/cell, P < 0.01) or low pesticide exposure (2.18 µm/cell, P < 0.01) had a significantly greater DNA tail moment than controls (1.28 µm/cell). Compared to the MDR1 T-129C (rs3213619) TC/CC carriers, the TT carriers had increased DNA tail moment in controls (1.30 versus 1.12 µm/cell, P < 0.01). Similar results were observed in the high and low pesticide-exposed groups. Combined analysis revealed that pesticide-exposed fruit growers with MDR1 -129 TT genotype had the greatest DNA damage in the subjects with the combinations of pesticide exposure and MDR1 -129 genotypes. In conclusion, pesticide exposed individuals with susceptible MDR1 -129 genotypes may experience increased risk of DNA damage.

Smoking, green tea consumption, genetic polymorphisms in the insulin-like growth factors and lung cancer risk.

Insulin-like growth factors (IGFs) are mediators of growth hormones; they have an influence on cell proliferation and differentiation. In addition, IGF-binding protein (IGFBP)-3 could suppress the mitogenic action of IGFs. Interestingly, tea polyphenols could substantially reduce IGF1 and increase IGFBP3. In this study, we evaluated the effects of smoking, green tea consumption, as well as IGF1, IGF2, and IGFBP3 polymorphisms, on lung cancer risk. Questionnaires were administered to obtain the subjects' characteristics, including smoking habits and green tea consumption from 170 primary lung cancer cases and 340 healthy controls. Genotypes for IGF1, IGF2, and IGFBP3 were identified by polymerase chain reaction. Lung cancer cases had a higher proportion of smoking, green tea consumption of less than one cup per day, exposure to cooking fumes, and family history of lung cancer than controls. After adjusting the confounding effect, an elevated risk was observed in smokers who never drank green tea, as compared to smokers who drank green tea more than one cup per day (odds ratio (OR) = 13.16, 95% confidence interval (CI) = 2.96-58.51). Interaction between smoking and green tea consumption on lung cancer risk was also observed. Among green tea drinkers who drank more than one cup per day, IGF1 (CA)(19)/(CA)(19) and (CA)(19)/X genotypes carriers had a significantly reduced risk of lung cancer (OR = 0.06, 95% CI = 0.01-0.44) compared with IGF1 X/X carriers. Smoking-induced pulmonary carcinogenesis could be modulated by green tea consumption and their growth factor environment.