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1.  Mediation Role of C-Reactive Protein on the Association between Smoking Quantity and Type 2 Diabetes in Current Chinese Smokers 
Journal of Diabetes Research  2014;2014:171538.
Objective. Previous studies have indicated that cigarette smokers are more likely to develop type 2 diabetes and that both smoking and type 2 diabetes are associated with C-reactive protein (CRP). This study examined whether CRP mediates the association between smoking quantity and type 2 diabetes. Methods. Nine hundred and eighty-four current Chinese smokers were selected from a community-based chronic disease survey conducted in Guangzhou and Zhuhai. Type 2 diabetes was defined according to the WHO 1999 criteria. CRP was measured with flow cytometry. Binary logistic regression was performed to assess the mediation. Results. A positive association was observed between smoking quantity and type 2 diabetes (P < 0.05). After controlling for potential confounders, daily cigarette consumption was significantly associated with higher CRP levels. Current smokers with type 2 diabetes had higher CRP levels than smokers without type 2 diabetes. The association between the smoking quantity and type 2 diabetes was mediated by CRP, which accounted for 50.77% of the association. Conclusions. This study provides further evidence that smoking quantity is positively associated with type 2 diabetes and suggests that the association between smoking and type 2 diabetes might be mediated by CRP.
PMCID: PMC4106084  PMID: 25105149
2.  Associations of CYP2A6 genotype with smoking behaviors in southern China 
Addiction (Abingdon, England)  2011;106(5):985-994.
To investigate the association of CYP2A6 genetic polymorphisms with smoking-related phenotypes in Chinese smokers.
Case-only genetic association study.
Southern China
A total of 1,328 Han Chinese smokers who participated in a community-based chronic disease screening project in Guangzhou and Zhuhai from 2006 to 2007.
All participants were answered a structured questionnaire about socio-demographic status and smoking behaviors and informative alleles for the cytochrome P450 2A6 (CYP2A6) gene (CYP2A6 *4, *5, *7, *9 and *10) were genotyped.
The frequencies of CYP2A6 *4, *5, *7, *9 and *10 alleles were 8.5%, 1.2%, 6.3%, 13.5% and 2.4%, which corresponded to 48.9%, 15.4%, 24.2% and 11.5% of participants being classified as normal, intermediate, slow and poor metabolizers, respectively. Multivariate analyses demonstrated that compared with normal metabolizers, poor metabolizers reported smoking fewer cigarettes per day (adjusted OR = 0.49; 95% CI: 0.32–0.76), started smoking regularly later in life (adjusted OR = 1.55; 95% CI: 1.06–2.26) and, amongst former smokers, reported smoking for a shorter duration prior to quitting (adjusted OR = 0.33; 95% CI: 0.12–0.94). However, poor metabolizers were less likely to quit smoking and remain abstinent than normal metabolizers (OR = 0.54; 95% CI: 0.34–0.86).
Reduced metabolism function of CYP2A6 in smokers appears to be associated with fewer cigarettes smoked, later initiation of smoking regularly, shorter smoking duration and lower likelihood of smoking cessation.
PMCID: PMC3074015  PMID: 21205058
CYP2A6; genetic polymorphisms; smoking behavior; Chinese smokers
3.  Anti–SARS-CoV Immunoglobulin G in Healthcare Workers, Guangzhou, China 
Emerging Infectious Diseases  2005;11(1):89-94.
Low level of immunity for SARS-CoV among well healthcare workers reinforces the need for infection control measures in hospitals to prevent epidemics.
To determine the prevalence of inapparent infection with severe acute respiratory syndrome (SARS) among healthcare workers, we performed a serosurvey to test for immunoglobulin (Ig) G antibodies to the SARS coronavirus (SARS-CoV) among 1,147 healthcare workers in 3 hospitals that admitted SARS patients in mid-May 2003. Among them were 90 healthcare workers with SARS. As a reference group, 709 healthcare workers who worked in 2 hospitals that never admitted any SARS patients were similarly tested. The seroprevalence rate was 88.9% (80/90) for healthcare workers with SARS and 1.4% (15/1,057) for healthcare workers who were apparently healthy. The seroprevalence in the reference group was 0.4% (3/709). These findings suggest that inapparent infection is uncommon. Low level of immunity among unaffected healthcare workers reinforces the need for adequate personal protection and other infection control measures in hospitals to prevent future epidemics.
PMCID: PMC3294349  PMID: 15705328
SARS; Seroprevalence; Healthcare workers; China; research
4.  CHRNA3 rs6495308 Genotype as an Effect Modifier of the Association between Daily Cigarette Consumption and Hypertension in Chinese Male Smokers 
Cigarette smoking is an important risk factor for hypertension. However, the effects on hypertension of the interaction between smoking and the genotype of the nicotinic acetylcholine receptor gene are unclear. The purpose of this study is to determine whether the CHRNA3 rs6495308 genotype affects the association between daily cigarette consumption and hypertension. We recruited 947 male smokers in southern China and used a questionnaire administered in face to face interviews to obtain information on their socio-demographic characteristics and smoking behavior. Blood samples were collected to test for CHRNA3 rs6495308 genotype variations. Three blood-pressure measurements were taken for each participant, and the average values recorded. We found that, compared with light smoking (<15 cigarettes per day), heavy smoking (≥15 cigarettes per day) yielded a greater risk of hypertension. We also observed that the interaction between daily cigarette consumption and the CHRNA3 rs6495308 genotype may affect hypertension. Heavy smokers with the homozygous mutant CHRNA3 rs6495308 genotype exhibited a significantly greater risk of hypertension than light smokers with wild-type CHRNA3 rs6495308 genotypes. The positive interaction between heavy smoking and the homozygous mutant CHRNA3 rs6495308 genotype was found to affect the likelihood of hypertension in Chinese male smokers.
PMCID: PMC4410239  PMID: 25874685
cigarette smoking; nicotine acetylcholine receptor; genotype; hypertension
5.  A Simple Risk Score for Identifying Individuals with Impaired Fasting Glucose in the Southern Chinese Population 
This study aimed to develop and validate a simple risk score for detecting individuals with impaired fasting glucose (IFG) among the Southern Chinese population. A sample of participants aged ≥20 years and without known diabetes from the 2006–2007 Guangzhou diabetes cross-sectional survey was used to develop separate risk scores for men and women. The participants completed a self-administered structured questionnaire and underwent simple clinical measurements. The risk scores were developed by multiple logistic regression analysis. External validation was performed based on three other studies: the 2007 Zhuhai rural population-based study, the 2008–2010 Guangzhou diabetes cross-sectional study and the 2007 Tibet population-based study. Performance of the scores was measured with the Hosmer-Lemeshow goodness-of-fit test and ROC c-statistic. Age, waist circumference, body mass index and family history of diabetes were included in the risk score for both men and women, with the additional factor of hypertension for men. The ROC c-statistic was 0.70 for both men and women in the derivation samples. Risk scores of ≥28 for men and ≥18 for women showed respective sensitivity, specificity, positive predictive value and negative predictive value of 56.6%, 71.7%, 13.0% and 96.0% for men and 68.7%, 60.2%, 11% and 96.0% for women in the derivation population. The scores performed comparably with the Zhuhai rural sample and the 2008–2010 Guangzhou urban samples but poorly in the Tibet sample. The performance of pre-existing USA, Shanghai, and Chengdu risk scores was poorer in our population than in their original study populations. The results suggest that the developed simple IFG risk scores can be generalized in Guangzhou city and nearby rural regions and may help primary health care workers to identify individuals with IFG in their practice.
PMCID: PMC4344664  PMID: 25625405
risk assessment; score; impaired fast glucose; Southern Chinese
6.  Relationship Between Amounts of Daily Cigarette Consumption and Abdominal Obesity Moderated by CYP2A6 Genotypes in Chinese Male Current Smokers 
Cigarette smoking is an important risk factor for abdominal obesity. However, the degree to which the CYP2A6 genotype moderates the relationship between smoking and abdominal obesity has not been established.
This study aims to investigate whether or not the relationship between smoking quantity and abdominal obesity is influenced by CYP2A6 genotypes.
Nine hundred fifty-four male current smokers were selected. A venous specimen was collected to test serum cotinine and CYP2A6 genotype, and all smokers were divided into heavy (>15 cigarettes/day) and light smokers (≤15 cigarettes/day).
Heavy smoking increased the risk of abdominal obesity (odds ratio (OR)=1.57; 95% CI, 1.13–2.19) compared with light smoking. Furthermore, heavy smoking had a positive interactive effect with CYP2A6 poor metabolizer genotype on abdominal obesity (OR=3.90; 95% CI, 1.25– 12.18). Moreover, CYP2A6 poor metabolizer genotypes were associated with slower nicotine metabolism.
Heavy smoking may increase the risk of abdominal obesity—particularly in smokers with CYP2A6 poor metabolizer genotypes.
PMCID: PMC4114962  PMID: 22160797
Cigarette smoking; CYP2A6 genotypes; Abdominal obesity; Interaction
7.  Interaction between heavy smoking and CYP2A6 genotypes on type 2 diabetes and its possible pathways 
To explore the interactions between smoking and CYP2A6 genotypes on type 2 diabetes (T2DM) as well as potential pathways for smoking in causing T2DM.
Cross-sectional study.
A total of 1344 smokers with complete data from a community-based T2DM survey in Guangzhou and Zhuhai of China from July 2006 to June 2007 were interviewed with a structured questionnaire about socio-demographic status and daily cigarette consumption. Serum glucose, insulin, and cotinine were measured after an overnight fast. Subjects were genotyped for CYP2A6 and classified, according to genotype, into normal, intermediate, slow, or poor nicotine metabolizers based on prior knowledge of CYP2A6 allele associations with nicotine C-oxidation rate. Abdominal obesity was defined as a waist-to-hip ratio ≥0.90 for males or ≥0.85 for females. Type 2 diabetic patients (n=154) were diagnosed according to WHO 1999 criteria. Chi-square tests, multivariate logistic regression models, and a structural equation model were used in this study.
Multivariate analysis indicated that, compared with light smoking, heavy smoking significantly increased the risk of T2DM (odds ratio (OR)=1.75, 95% CI=1.01–3.05). There were significant interactions between heavy smoking and slow CYP2A6 (OR=5.12, 95% CI=1.08–24.23) and poor CYP2A6 metabolizer genotypes (OR=8.54, 95% CI=1.28–57.02) on T2DM. Structural equation modeling indicated that CYP2A6 moderation of smoking quantity risk on T2DM was mediated by the effects on serum cotinine, abdominal obesity, insulin resistance, and insulin secretion.
Heavy smoking was significantly associated with T2DM, and this association was moderated by CYP2A6 genotype and mediated by serum cotinine, abdominal obesity, insulin resistance, and insulin secretion.
PMCID: PMC4112659  PMID: 21964962
8.  Comparison of Predictive Value of Cardiometabolic Indices for Subclinical Atherosclerosis in Chinese Adults 
PLoS ONE  2014;9(4):e93538.
Metabolic disturbances are well-known risk factors for atherosclerosis, but it remains unclear which cardiometabolic components are the predominant determinants. This study aimed to compare and identify the key determinants of carotid atherosclerosis in asymptomatic middle-aged and elderly Chinese.
A community-based cross-sectional study including 3,162 apparently healthy residents aged 37–75 years was performed from July 2008 to June 2010 in Guangzhou, China. Carotid artery intima-media thickness (IMT) was assessed by B-mode ultrasound, and increased IMT was defined as IMT>1.00 mm. Obesity indices, blood pressure, fasting blood lipids, glucose and uric acid levels were determined. Principal components factor analysis was used to extract common factors underlying 11 metabolic factors.
Four common factors, defined as “adiposity,” “blood lipids,” “triglycerides/uric acid (TG/UA)” (in men) or “triglycerides/uric acid/glucose (TG/UA/Glu)” (in women), and “blood pressure,” were retained for both sexes. After adjustment for potential covariates, the “adiposity” factor showed the strongest positive association with increased IMT in men. Comparing the extreme quartiles, ORs (95% CI) of increased IMT were 4.64 (2.04–10.59) at the CCA and 2.37 (1.54–3.64) at the BIF), followed by “blood pressure”, the corresponding OR (95% CI) was 2.85 (1.37–5.90) at the CCA. Whereas, the four common factors showed comparable and weak relationship with increased IMTs, the ORs for quartile 4 vs. quartile 1 varied from 0.89 to 3.59 in women.
Among the metabolic factors, “adiposity” and “blood pressure” play predominant roles in the presence of carotid atherosclerosis in men, but no key factor is identified in women.
PMCID: PMC3972246  PMID: 24691185
9.  Interaction between Maternal Passive Smoking during Pregnancy and CYP1A1 and GSTs Polymorphisms on Spontaneous Preterm Delivery 
PLoS ONE  2012;7(11):e49155.
The present study aimed to examine the association between maternal passive smoking during pregnancy and the risk of spontaneous PTD and to explore the potential interaction of the single or joint gene polymorphism of CYP1A1 and GSTs with maternal passive smoking on the risk of spontaneous PTD.
We investigated whether the association between maternal passive smoking and PTD can be modified by 2 metabolic genes, i.e. cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTs), in a case-control study with 198 spontaneous preterm and 524 term deliveries in Shenzhen and Foshan, China. We used logistic regression to test gene-passive smoking interaction, adjusting for maternal socio-demographics and prepregnancy body mass index.
Overall, maternal passive smoking during pregnancy was associated with higher risk of PTD (adjusted odds ratio = 2.20 [95% confidence interval: 1.56–3.12]). This association was modified by CYP1A1 and GSTs together, but not by any single genotype. For cross-categories of CYP1A1 Msp I and GSTs, maternal passive smoking was associated with higher risk of PTD among those women with CYP1A1 “TC/CC”+ GSTs “null”, but not among women with other genotypes; and this interaction was significant (OR = 2.66 [95% CI: 1.19–5.97]; P-value: 0.017). For cross-categories of CYP1A1 BsrD I and GSTs, maternal passive smoking was associated with higher risk of PTD only among those women with CYP1A1“AG/GG”+ GSTs “null”, but not among women with other genotypes; and this interaction was significant (OR = 3.00 [95% CI: 1.17–7.74]; P-value: 0.023).
Our findings suggest that the combined genotypes of CYP1A1 and GSTs can help to identify vulnerable pregnant women who are subject to high risk of spontaneous PTD due to passive smoking.
PMCID: PMC3496734  PMID: 23152866
10.  Joint Effects of Febrile Acute Infection and an Interferon-γ Polymorphism on Breast Cancer Risk 
PLoS ONE  2012;7(5):e37275.
There is an inverse relationship between febrile infection and the risk of malignancies. Interferon gamma (IFN-γ) plays an important role in fever induction and its expression increases with incubation at fever-range temperatures. Therefore, the genetic polymorphism of IFN-γ may modify the association of febrile infection with breast cancer risk.
Methodology and Principal Findings
Information on potential breast cancer risk factors, history of fever during the last 10 years, and blood specimens were collected from 839 incident breast cancer cases and 863 age-matched controls between October 2008 and June 2010 in Guangzhou, China. IFN-γ (rs2069705) was genotyped using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. We found that women who had experienced ≥1 fever per year had a decreased risk of breast cancer [ORs and 95% CI: 0.77 (0.61–0.99)] compared to those with less than one fever a year. This association only occurred in women with CT/TT genotypes [0.54 (0.37–0.77)] but not in those with the CC genotype [1.09 (0.77–1.55)]. The association of IFN-γ rs2069705 with the risk of breast cancer was not significant among all participants, while the CT/TT genotypes were significantly related to an elevated risk of breast cancer [1.32 (1.03–1.70)] among the women with <1 fever per year and to a reduced risk of breast cancer [0.63 (0.40–0.99)] among women with ≥1 fever per year compared to the CC genotype. A marked interaction between fever frequencies and the IFN-γ genotypes was observed (P for multiplicative and additive interactions were 0.005 and 0.058, respectively).
Our findings indicate a possible link between febrile acute infection and a decreased risk of breast cancer, and this association was modified by IFN-γ rs2069705.
PMCID: PMC3356273  PMID: 22624006
11.  Cigarette Smoking and p16INK4α Gene Promoter Hypermethylation in Non-Small Cell Lung Carcinoma Patients: A Meta-Analysis 
PLoS ONE  2011;6(12):e28882.
Aberrant methylation of promoter DNA and transcriptional repression of specific tumor suppressor genes play an important role in carcinogenesis. Recently, many studies have investigated the association between cigarette smoking and p16INK4α gene hypermethylation in lung cancer, but could not reach a unanimous conclusion.
Methods and Findings
Nineteen cross-sectional studies on the association between cigarette smoking and p16INK4α methylation in surgically resected tumor tissues from non-small cell lung carcinoma (NSCLC) patients were identified in PubMed database until June 2011. For each study, a 2×2 cross-table was extracted. In total, 2,037 smoker and 765 nonsmoker patients were pooled with a fixed-effects model weighting for the inverse of the variance. Overall, the frequency of p16INK4α hypermethylation was higher in NSCLC patients with smoking habits than that in non-smoking patients (OR = 2.25, 95% CI = 1.81–2.80). The positive association between cigarette smoking and p16INK4α hypermethylation was similar in adenocarcinoma and squamous-cell carcinoma. In the stratified analyses, the association was stronger in Asian patients and in the studies with larger sample sizes.
Cigarette smoking is positively correlated to p16INK4α gene hypermethylation in NSCLC patients.
PMCID: PMC3236763  PMID: 22174919
12.  Cancer mortality in a Chinese population surrounding a multi-metal sulphide mine in Guangdong province: an ecologic study 
BMC Public Health  2011;11:319.
The Dabaoshan mine in the southeast of Guangdong Province, China, is at high risk of multi-metal pollutant discharge into a local river (Hengshihe) and the surrounding area. Following approximately 30 years of exposure to these metals, little is known regarding the subsequent health effects and risks for the local residents. In our present study, we have estimated the relationships between long-term environmental exposure to multiple heavy metals and the risk of cancer mortality in a Chinese population in the vicinity of Dabaoshan.
An ecologic study was performed. Between 2000-2007, a total population of 194,131 lived in the nine agricultural villages that surround the Hengshihe area. Heavy metals concentrations were determined in local environmental samples (water and crops) and whole blood taken from 1152 local residents of both a high-exposure area (HEA) and a low-exposure area (LEA). We calculated the rate ratio and standardized mortality ratios based on age- and gender-specific cancer mortality rates for the different reference populations (based on district, county and province). Simple, multiple linear and ridge regression models were used to evaluate the associations between exposure to multiple heavy metals and cancer mortality in the nine villages, after adjustment for age and sex.
The geometric mean blood levels of cadmium and lead were measured at 24.10 μg/L and 38.91 μg/dL for subjects (n = 563) in the HEA and 1.87 μg/L and 4.46 μg/dL for subjects (n = 589) from the LEA, respectively (P < 0.001). The rate of mortality from all cancers in the HEA was substantially elevated in comparison with the corresponding mortality rate in the LEA for men (rate ratio = 2.13; 95% confidence intervals = 1.63 - 2.77) and women (2.83; 1.91 - 4.19); rates were also significantly elevated compared with the rate when compared to the entire Wengyuan County area, or the provincial reference population. In addition, mortality rates were significantly increased for stomach, lung and esophageal cancer in the HEA in comparison with the corresponding rates in the LEA, in Wengyuan County and the provincial reference population for men, women and both combined. Further analysis showed that there were significantly positive correlations between exposure to cadmium and lead and the risk of all-cancers and stomach cancer mortality among women and both sexes, whilst zinc exposure showed no association with the risk of site-specific cancer mortality in the nine villages evaluated.
The findings of this study reveal probable associations between long-term environmental exposure to both cadmium and lead and an increased risk of mortality from all cancer, as well as from stomach, esophageal and lung-cancers.
PMCID: PMC3112132  PMID: 21575207
13.  Behavioural development of school-aged children who live around a multi-metal sulphide mine in Guangdong province, China: a cross-sectional study 
BMC Public Health  2009;9:217.
The deleterious biological effects of low-level, long-term exposure to heavy metals are well known, and children are the most susceptible population. Dabaoshan Mine in the southeast of Guangdong Province is at high risk of discharging multi-metals pollutants into a local river (Hengshihe) and the surrounding area. The present study aimed to estimate relationships between measured multi-metal exposures and the presence of behavioural problems for the school-aged children in the polluted area.
A cross-sectional study was performed. Children aged 7–16 years living in three villages of the Hengshihe area with different degrees of heavy-metal pollution participated in this study. Local environmental samples (water and crops) and children's hair were collected, and concentrations of heavy metals were determined. The Child Behaviour Check-list (CBCL) was used to assess the presence of behaviour problems. General linear regression was used to analyze the contribution of hair metals to each CBCL subscale with adjustment for socio-demographic confounding factors.
Multiple regression analyses revealed significant effects of hair lead, cadmium and zinc levels on CBCL subscales. Log-transformed hair lead, cadmium and zinc levels accounted for an incremental of 8% to 15% variance in anxious/depressed, withdrawn, somatic complaints, social problems, thought problems, attention problems, delinquent behaviour and aggressive behaviour. The concurrent log-transformed hair lead and zinc levels were strongly associated with all subscales while the concurrent log-transformed hair cadmium was only significantly associated with withdrawn, social problems and attention problems.
This study reveals that heavy metal exposure was associated with increased risk of behavioral problems for school-aged children.
PMCID: PMC2717083  PMID: 19573251
14.  Which preventive measures might protect health care workers from SARS? 
BMC Public Health  2009;9:81.
Despite the use of a series of preventive measures, a high incidence of severe acute respiratory syndrome (SARS) was observed among health care workers (HCWs) during the SARS epidemic. This study aimed to determine which preventive measures may have been effective in protecting HCWs from infection, and which were not effective.
A retrospective study was performed among 758 'frontline' health care workers who cared for SARS patients at the Second Affiliated Hospital and the Third Affiliated Hospital of Sun Yat-sen University. The HCWs with IgG against SARS and those without IgG against SARS were respectively defined as the "case group" and the "control group", and logistic regression was conducted to explore the risk factors for SARS infection in HCWs.
After adjusting for age, gender, marital status, educational level, professional title, and the department in which an individual worked, the results of a multivariate logistic regression analysis indicated that incidence of SARS among HCWs was significantly and positively associated with: performing tracheal intubations for SARS patients, methods used for air ventilation in wards, avoiding face-to-face interaction with SARS patients, the number of pairs of gloves worn by HCWs, and caring for serious SARS cases.
Some measures, particularly good air ventilation in SARS wards, may be effective in minimizing or preventing SARS transmission among HCWs in hospitals.
PMCID: PMC2666722  PMID: 19284644

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