Shaofa Nie

Genetic variations in the TGFβ signaling pathway, smoking, and risk of colorectal cancer in a Chinese population

Recent genome-wide association studies (GWAS) have reported multiple risk loci associated with risk of colorectal cancer (CRC), some of which are involved in the transforming growth factor beta (TGFβ) signaling pathway. We systematically examined associations of common genetic variations in the TGFβ signaling pathway and environmental factors with CRC risk using a two-staged case-control study in a Chinese population. A set of 77 single-nucleotide polymorphisms (SNPs) in 10 candidate genes involved in the TGFβ signaling pathway and several environmental factors including sex, age, smoking and drinking were examined by random forest (RF) to capture the potential gene-gene and gene-environment interactions in stage 1 of the study with 443 CRC patients and 480 controls. Three promising SNPs (SMAD7 rs11874392, TGFBR1 rs10988706 and rs6478972) selected by the RF method were genotyped in stage 2 comprising 351 cases and 360 controls for validation. SMAD7 rs11874392 presented consistently significant associations with a risk of CRC at both stages, with odds ratio = 1.41 (95% confidence interval = 1.21-1.63) using additive modes in combined analyses. Moreover, the potential interactions between SMAD7 rs11874392, TGFBR1 rs10988706 and rs6478972 were indicated consistently in both stages of the study by using pair-wise interaction and multilocus genotype pattern analysis. Additionally, gene-smoking interactions for rs11874392, rs10988706 and rs6478972 were also found to enhance the risk of CRC at both stages, with P for multiplicative interaction equal to 1.162×10(-6), 8.574×10(-8) and 9.410×10(-8) in combined analyses, respectively. This study emphasized the substantial role of the TGFβ signaling pathway in CRC, especially in interaction with smoking.

The dose–response effect of physical activity on cancer mortality: findings from 71 prospective cohort studies

Background The WHO recommends moderate physical activity to combat the increasing risk of death from chronic diseases. We conducted a meta-analysis to assess the association between physical activity and cancer mortality and the WHO recommendations to reduce the latter. Methods MEDLINE and EMBASE were searched up until May 2014 for cohort studies examining physical activity and cancer mortality in the general population and cancer survivors. Combined HRs were estimated using fixed-effect or random-effect meta-analysis of binary analysis. Associated HRs with defined increments and recommended levels of recreational physical activity were estimated by two-stage random-effects dose–response meta-analysis. Results A total of 71 cohort studies met the inclusion criteria and were analysed. Binary analyses determined that individuals who participated in the most physical activity had an HR of 0.83 (95% CI 0.79 to 0.87) and 0.78 (95% CI 0.74 to 0.84) for cancer mortality in the general population and among cancer survivors, respectively. There was an inverse non-linear dose–response between the effects of physical activity and cancer mortality. In the general population, a minimum of 2.5 h/week of moderate-intensity activity led to a significant 13% reduction in cancer mortality. Cancer survivors who completed 15 metabolic equivalents of task (MET)-h/week of physical activity had a 27% lower risk of cancer mortality. A greater protective effect occurred in cancer survivors undertaking physical activity postdiagnosis versus prediagnosis, where 15 MET-h/week decreased the risk by 35% and 21%, respectively. Conclusions Our meta-analysis supports that current physical activity recommendations from WHO reduce cancer mortality in both the general population and cancer survivors. We infer that physical activity after a cancer diagnosis may result in significant protection among cancer survivors.

Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey

BackgroundChina is at greatest risk of the Pandemic (H1N1) 2009 due to its huge population and high residential density. The unclear comprehension and negative attitudes towards the emerging infectious disease among general population may lead to unnecessary worry and even panic. The objective of this study was to investigate the Chinese public response to H1N1 pandemic and provide baseline data to develop public education campaigns in response to future outbreaks.MethodsA close-ended questionnaire developed by the Chinese Center for Disease Control and Prevention was applied to assess the knowledge, attitudes and practices (KAP) of pandemic (H1N1) 2009 among 10,669 responders recruited from seven urban and two rural areas of China sampled by using the probability proportional to size (PPS) method.Results30.0% respondents were not clear whether food spread H1N1 virusand. 65.7% reported that the pandemic had no impact on their life. The immunization rates of the seasonal flu and H1N1vaccine were 7.5% and 10.8%, respectively. Farmers and those with lower education level were less likely to know the main transmission route (cough or talk face to face). Female and those with college and above education had higher perception of risk and more compliance with preventive behaviors. Relationships between knowledge and risk perception (OR = 1.69; 95%CI 1.54-1.86), and knowledge and practices (OR = 1.57; 95%CI 1.42-1.73) were found among the study subjects. With regard to the behavior of taking up A/H1N1 vaccination, there are several related factors found in the current study population, including the perception of life disturbed (OR = 1.29; 95%CI 1.11-1.50), the safety of A/H1N1 vaccine (OR = 0.07; 95%CI 0.04-0.11), the knowledge of free vaccination policy (OR = 7.20; 95%CI 5.91-8.78), the states priority vaccination strategy(OR = 1.33; 95%CI 1.08-1.64), and taking up seasonal influenza vaccine behavior (OR = 4.69; 95%CI 3.53-6.23).ConclusionsThis A/H1N1 epidemic has not caused public panic yet, but the knowledge of A/H1N1 in residents is not optimistic. Public education campaign may take the side effects of vaccine and the knowledge about the states vaccination strategy into account.

Association of candidate genetic variations with gastric cardia adenocarcinoma in Chinese population: a multiple interaction analysis

Single genetic variation may only have a modest effect on risk of gastric cardia adenocarcinoma (GCA) because this malignancy is believed to result from complex interactions among multiple genetic and environmental factors. However, it has been a challenge to characterize multiple interactions using parametric analytic approaches. This study utilized a multi-analytic strategy combining logistic regression (LR), multifactor dimensionality reduction (MDR) and classification and regression tree (CART) approaches to explore high-order interactions among smoking and 12 polymorphisms involved in different processes of carcinogenesis in 344 GCA patients and 324 controls. LR, MDR and CART analyses consistently suggested MMP-2 C-1306T polymorphism as the strongest individual factor for GCA risk. Intriguingly, a high-order interaction was consistently identified by MDR, LR and CART analyses. In MDR analysis, the three-factor model including MMP-2 C-1306T, FASL T-844C and FAS G-1377A yielded the highest testing accuracy of 0.632. When analysing combined effect of these three polymorphisms by LR, a significant gene dose effect was observed with the odds ratios (ORs) being increased with increasing numbers of risk genotypes (P(trend) = 4.736 × 10⁻¹²). In CART analysis, individuals carrying the combined genotypes of MMP-2 -1306CC, FASL-844TT or TC and FAS -1377AA had the highest risk for GCA (OR = 4.58; 95% confidence interval, 2.07-10.14) compared with the lowest risk carriers of the MMP-2 -1306CT or TT genotype. These results suggest that MMP-2 C-1306T polymorphism is an important risk factor for GCA and the multifactor interactions among polymorphisms in MMP-2, FASL and FAS play more important role in the development of GCA.

Interactions between Genetic Variants in the Adiponectin, Adiponectin Receptor 1 and Environmental Factors on the Risk of Colorectal Cancer

Background Metabolic syndrome traits play an important role in the development of colorectal cancer. Adipokines, key metabolic syndrome cellular mediators, when abnormal, may induce carcinogenesis. Methodology/Principal Findings To investigate whether polymorphisms of important adipokines, adiponectin (ADIPOQ) and its receptors, either alone or in combination with environmental factors, are implicated in colorectal cancer, a two-stage case-control study was conducted. In the first stage, we evaluated 24 tag single nucleotide polymorphisms (tag SNPs) across ADIPOQ ligand and two ADIPOQ receptors (ADIPOR1 and ADIPOR2) among 470 cases and 458 controls. One SNP with promising association was then analyzed in stage 2 among 314 cases and 355 controls. In our study, ADIPOQ rs1063538 was consistently associated with increased colorectal cancer risk, with an odds ratio (OR) of 1.94 (95%CI: 1.48–2.54) for CC genotype compared with TT genotype. In two-factor gene-environment interaction analyses, rs1063538 presented significant interactions with smoking status, family history of cancer and alcohol use, with ORs of 4.52 (95%CI: 2.78–7.34), 3.18 (95%CI: 1.73–5.82) and 1.97 (95%CI: 1.27–3.04) for smokers, individuals with family history of cancer or drinkers with CC genotype compared with non-smokers, individuals without family history of cancer or non-drinkers with TT genotype, respectively. Multifactor gene-environment interactions analysis revealed significant interactions between ADIPOQ rs1063538, ADIPOR1 rs1539355, smoking status and BMI. Individuals carrying one, two and at least three risk factors presented 1.18–fold (95%CI:0.89–fold to 1.58–fold), 1.87–fold (95%CI: 1.38–fold to2.54–fold) and 4.39–fold (95%CI: 2.75–fold to 7.01–fold) increased colorectal cancer risk compared with those who without risk factor, respectively (P trend <0.0001). Conclusions/Significance Our results suggest that variants in ADIPOQ may contribute to increased colorectal cancer risk in Chinese and this contribution may be modified by environmental factors, such as smoking status, family history of cancer and BMI.

Combined Effect of Genetic Polymorphisms in P53, P73, and MDM2 on Non-small Cell Lung Cancer Survival

Introduction: Multiple biologically relevant polymorphisms may have more accurate prediction of cancer prognosis compared with single polymorphism because of the modest effect. This study investigated whether the functional polymorphisms in P53 pathway genes, P53 Arg72Pro (rs1042522), P73 G4C14-to-A4T14 (rs2273953 and rs1801173), and MDM2 T309G (rs2279744), alone or in combination, affect survival in advanced non-small cell lung cancer (NSCLC) patients. Methods: A total of 199 stage III–IV NSCLC patients with platinum-based chemotherapy were recruited between 2002 and 2004. Associations between genotypes and survival were assessed using Kaplan-Meier method. Cox proportional hazard models were performed to identify significant variables. Results: During the median 26.5 months of follow-up, the P53 Pro/Pro genotype was strongly associated with shorter overall survival compared with the Arg/Arg genotype (12.0 versus 20.0 months; log-rank p = 0.002; hazard ratio = 1.86; 95% confidence interval [CI], 1.15–3.02). Pairwise combination analysis showed that patients carrying the variant P53 Pro/Pro-P73 GC/GC or P53 Pro/Pro-MDM2 GG genotypes had survival time only half of that for those carrying the wild-type genotypes, with hazard ratio being 2.47 (95% CI, 1.20–5.10) and 2.00 (95% CI, 1.15–3.46), respectively. Furthermore, a combined effect was seen with survival time being gradually shorter with increasing number of unfavorable genotypes in these three genes (ptrend = 0.039), indicating a gene-dose effect in association with survival. Conclusions: These findings suggest that genetic polymorphisms in the P53 pathway may be promising biomarkers for individualized chemotherapy and prognosis of NSCLC patients.

A functional polymorphism (-1607 1G→2G) in the matrix metalloproteinase-1 promoter is associated with development and progression of lung cancer.

Matrix metalloproteinase‐1 (MMP‐1), an interstitial collagenase, plays an important role in the breakdown of extracellular matrix and mediates pathways of apoptosis, angiogenesis, and immunity. It has been demonstrated that the overexpression of this enzyme is associated with tumor initiation, invasion, and metastasis. The −1607 single guanine (1G)‐to‐2G polymorphism (reference single nucleotide polymorphism 1799750) in the MMP‐1 promoter region creates an E26 (Ets) binding site and results in transcriptional up‐regulation. The authors hypothesized that this MMP‐1 polymorphism may affect susceptibility to the development and progression of cancer.

Point prevalence surveys of healthcare-associated infection in 13 hospitals in Hubei Province, China, 2007-2008

Successive point prevalence surveys were conducted in November 2007 and 2008 to monitor the prevalence of healthcare-associated infection (HCAI) in 13 grade III, 1st class hospitals in Hubei Province of China, using the case definition criteria established by the Ministry of Health in the Peoples Republic of China. In total, of 20 350 patients surveyed, 833 (4.09%) HCAIs were observed in 790 (3.88%) patients. There was no significant difference between the overall prevalence of HCAI in 2007 (4.14%) and 2008 (3.72%). Respiratory tract infection was the most common HCAI (63.15%), followed by surgical site infection (9.60%) and urinary tract infection (8.64%). Only 35.29% (294/833) of HCAI patients had positive microbiology results. Gram-negative bacteria were isolated most frequently and the most frequent organism was Pseudomonas aeruginosa, followed by Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus. Antibiotic use was documented for 10,344 (50.83%) patients, and cephalosporins, penicillins, and quinolones were the most commonly used agents for treatment or prophylaxis.

Assessment of XPD Lys751Gln and XRCC1 T–77C polymorphisms in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy

Polymorphisms in DNA repair genes were thought to represent important determinants of platinum drug efficacy. This study tested whether XPD Lys751Gln and XRCC1 T-77C polymorphisms were associated with survival in platinum-treated patients with advanced non-small-cell lung cancer (NSCLC). In this study, 199 advanced NSCLC patients with platinum-based chemotherapy were recruited. During the median 26.5 months of follow-up, patients with the XPD 751Lys/Lys genotype had a median survival time of 17.0 months (95% CI, 14.5-19.6 months), not much longer than those carried Lys/Gln heterozygote (12.0 months; 95% CI, 3.4-20.6 months; log-rank test, P=0.542). In Cox proportional hazards model, no significant associations were found between XPD Lys751Gln polymorphism and survival. For XRCC1 T-77C polymorphism, the median survival of patients with TC+CC genotype (18 months; 95% CI, 13.5-22.5 months) was similar to those with the TT genotype (16.0 months; 95% CI, 13.3-18.7 months; log-rank test, P=0.399). XRCC1 T-77C polymorphism was not associated with survival in Cox proportional hazards model. Additionally, the analysis for combination of these two polymorphisms also showed no prognostic significance for NSCLC. Our findings indicated that neither XPD Lys751Gln nor XRCC1 T-77C could be genetic determinant for prognosis of advanced NSCLC patients treated with platinum-based chemotherapy.

Evaluating the effectiveness of an emergency preparedness training programme for public health staff in China

Summary Background The severe acute respiratory syndrome (SARS) crisis of 2003 provided a new urgency in China in terms of preparing public health staff to respond effectively to public health emergencies. Although the Chinese Government has already carried out a series of emergency education and training programmes to improve public health staffs capability of emergency preparedness, it remains unclear if these training programmes are effective and feasible. The purpose of this research was to evaluate an emergency preparedness training programme and to develop a participatory training approach for emergency response. Methods Seventy-six public health staff completed the emergency preparedness training programme. The effectiveness of the training was evaluated by questionnaire before training, immediately after training and 12 months after training (follow-up). Additionally, semi-structured interviews were conducted throughout the training period. Results The emergency preparedness training improved the knowledge levels and increased attitudinal and behavioural intention scores for emergency preparedness (P<0.01). The results at follow-up showed that the knowledge levels and attitudinal/behavioural intention scores of participants decreased slightly (P>0.05) compared with levels immediately after training (P<0.01). However, there was a significant increase compared with before training (P<0.01). Moreover, more than 80% of participants reported that the training process and resources were scientific and feasible. Conclusions The emergency preparedness training programme met its aims and objectives satisfactorily, and resulted in positive shifts in knowledge and attitudinal/behavioural intentions for public health staff. This suggests that this emergency training strategy was effective and feasible in improving the capability of emergency preparedness.