Distribution of hepatitis C virus in eastern China from 2011 to 2020: a Bayesian spatiotemporal analysis.

Objective: This study aimed to evaluate the spatiotemporal distribution of patients with hepatitis C virus (HCV) and the factors influencing this distribution in Jiangsu Province, China, from 2011 to 2020. Methods: The incidence of reported HCV in Jiangsu Province from 2011 to 2020 was obtained from the Chinese Information System for Disease Control and Prevention (CISDCP). R and GeoDa software were used to visualize the spatiotemporal distribution and the spatial autocorrelation of HCV. A Bayesian spatiotemporal model was constructed to explore the spatiotemporal distribution of HCV in Jiangsu Province and to further analyze the factors related to HCV. Results: A total of 31,778 HCV patients were registered in Jiangsu Province. The registered incidence rate of HCV increased from 2.60/100,000 people in 2011 to 4.96/100,000 people in 2020, an increase of 190.77%. Moran's I ranged from 0.099 to 0.354 (P < 0.05) from 2011 to 2019, indicating a positive spatial correlation overall. The relative risk (RR) of the urbanization rate, the most important factor affecting the spread of HCV in Jiangsu Province, was 1.254 (95% confidence interval: 1.141-1.376), while other factors had no significance. Conclusion: The reported HCV incidence rate integrally increased in the whole Jiangsu Province, whereas the spatial aggregation of HCV incidence was gradually weakening. Our study highlighted the importance of health education for the floating population and reasonable allocation of medical resources in the future health work.

Histogram Analysis of Quantitative Susceptibility Mapping for the Diagnosis of Parkinson's Disease.

RATIONALE AND OBJECTIVES: To investigate the diagnostic performance of histogram analysis combined with quantitative susceptibility mapping (QSM) for differentiating Parkinson's disease (PD) patients from healthy controls. METHODS: We included 35 patients with PD diagnosed by two neurologists from August 2019 to January 2020 in our hospital in this prospective study. The clinical diagnosis was based on the Movement Disorder Society Clinical Diagnostic Criteria for PD. At the same time, 23 healthy volunteers matched for age and sex were recruited as controls. The Mini Mental State Examination, the third part of the Parkinson's Disease Rating Scale, the Hoehn & Yahr stages, and disease duration (year) were used to assess the PD patients. QSM was performed using a 3T MR scanner. The regions of interest were depicted according to the head of the caudate nucleus(CN), globus pallidus(GP), putamina (PUT), thalmus(TH), substantia nigra (SN), red nucleus(RN), and dentate nucleus. Then the corresponding histogram features were extracted. The Mann-Whitney U test was used to identify significant histogram features for differentiating PD patients from healthy controls. Area under the receiver operating characteristics curve (AUC) analysis was conducted to evaluate the diagnostic performance of all significant histogram features. Multivariate logistic regression analysis was performed to identify the best combined model for all seven nuclei. Differences among the AUCs were compared pairwise. RESULTS: Histogram features in all nuclei except TH showed significant differences between the groups. Among the single features, the 10th percentile of SN (SNP10) yielded the highest AUC of 0.894, with the highest specificity of 86.86% for differentiating PD patients from healthy controls. The 75th percentile of PUT (PUTP75) yielded the highest sensitivity of 97.14%. In the multivariate logistic regression analysis, SNP10 combined with PUTP75 yielded the highest diagnostic performance with the highest AUC of 0.911, the highest specificity of 91.30% and an excellent sensitivity of 92.40%. CONCLUSION: QSM combined with histogram analysis successfully distinguished PD patients from healthy controls, and the result was notably superior to the mean value.

Association Between Small Vessel Disease Markers, Medial Temporal Lobe Atrophy and Cognitive Impairment After Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVES: Two-thirds of stroke survivors suffer from cognitive impairment, and up to one-third of them progress to dementia. However, the underlying pathogenesis is complex and controversial. Recent evidence has found that cerebral small vessel disease (SVD) markers and the Alzheimer's disease (AD) neuroimaging marker medial temporal lobe atrophy (MTLA), alone or in combination, contribute to the pathogenesis of poststroke cognitive impairment (PSCI). In the present systematic review and meta-analysis, we synthesized proof for these neuroimaging risk factors among stroke patients. MATERIALS AND METHODS: PUBMED, MEDLINE, EMBASE and the Cochrane Library were searched for studies investigating imaging predictors of cognitive impairment or dementia following stroke. Meta-analysis was conducted to compute the odds ratios (ORs). RESULTS: Thirteen studies were enrolled in the present study, and only ten of them, comprising 2713 stroke patients, were eligible for inclusion in the meta-analysis. MTLA was significantly correlated with PSCI (OR = 1.97, 95% CI: 1.48-2.62, I2 = 0.0%). In addition, white matter hyperintensities (WMH), as a neuroimaging marker of SVD, were associated with PSCI (OR = 1.17, 95% CI: 1.12-1.22, I2 = 0.0%). However, the presence of lacunar infarcts and enlarged perivascular spaces (EPVS) were not associated with the risk of PSCI. CONCLUSIONS: The findings of the present study suggest that MTLA and WMH were associated with an increased risk of PSCI.

Iron deposition in Parkinson's disease by quantitative susceptibility mapping.

BACKGROUND: Patients with Parkinson's disease (PD) have elevated levels of brain iron, especially in the nigrostriatal dopaminergic system. The purpose of this study was to evaluate the iron deposition in the substantia nigra (SN) and other deep gray matter nuclei of PD patients using quantitative susceptibility mapping (QSM) and its clinical relationship, and to explore whether there is a gradient of iron deposition pattern in globus pallidus (GP)-fascicula nigrale (FN)-SN pathway. METHODS: Thirty-three PD patients and 26 age- and sex-matched healthy volunteers (HVs) were included in this study. Subjects underwent brain MRI and constructed QSM data. The differences in iron accumulation in the deep gray matter nuclei of the subjects were compared, including the PD group and the control group, the early-stage PD (EPD) group and the late-stage PD (LPD) group. The iron deposition pattern of the GP-FN-SN pathway was analyzed. RESULTS: The PD group showed increased susceptibility values in the FN, substantia nigra pars compacta (SNc), internal globus pallidus (GPi), red nucleus (RN), putamen and caudate nucleus compared with the HV group (P < 0.05). In both PD and HV group, iron deposition along the GP-FN-SN pathway did not show an increasing gradient pattern. The SNc, substantia nigra pars reticulata (SNr) and RN showed significantly increased susceptibility values in the LPD patients compared with the EPD patients. CONCLUSION: PD is closely related to iron deposition in the SNc. The condition of PD patients is related to the SNc and the SNr. There is not an increasing iron deposition gradient along the GP-FN-SN pathway. The source and mechanism of iron deposition in the SN need to be further explored, as does the relationship between the iron deposition in the RN and PD.

Association between the Angiotensin-Converting Enzyme (ACE) Genetic Polymorphism and Diabetic Retinopathy-A Meta-Analysis Comprising 10,168 Subjects.

Aims-to address the inconclusive findings of the association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on risk of diabetic retinopathy (DR), a meta-analysis was conducted. Methods-we conducted a meta-analysis on 4252 DR cases and 5916 controls from 40 published studies by searching electronic databases and reference lists of relevant articles. A random-effects or fixed-effects model was used to estimate the overall and stratification effect sizes on ACE I/D polymorphism on the risk of DR. Results-we found a significant association between the ACE I/D polymorphism and the risk of DR for all genetic model (ID vs. II: OR = 1.14, 95% CI: 1.00-1.30; DD vs. II: OR = 1.38, 95% CI: 1.11-1.71; Allele contrast: OR = 1.17, 95% CI: 1.05-1.30; recessive model: OR = 1.24, 95% CI: 1.02-1.51 and dominant model: OR = 1.21, 95% CI: 1.06-1.38, respectively). In stratified analysis by ethnicity and DM type, we further found that the Asian group with T2DM showed a significant association for all genetic models (ID vs. II: OR = 1.14, 95% CI: 1.01-1.30; DD vs. II: OR = 1.54, 95% CI: 1.14-2.08; Allele contrast: OR = 1.26, 95% CI: 1.09-1.47; recessive model: OR = 1.42, 95% CI: 1.07-1.88 and dominant model: OR = 1.26, 95% CI: 1.07-1.49, respectively). Conclusion-our study suggested that the ACE I/D polymorphism may contribute to DR development, especially in the Asian group with type 2 diabetes mellitus (T2DM). Prospective and more genome-wide association studies (GWAS) are needed to clarify the real role of the ACE gene in determining susceptibility to DR.

A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy.

AIMS: To shed light on the conflicting findings of the association between the methylenetetrahydrofolate reductase gene (MTHFR) 677C/T polymorphism and the risk of diabetic retinopathy (DR), a meta-analysis was conducted. METHODS: A predefined search was performed on 1747 DR cases and 3146 controls from 18 published studies by searching electronic databases and reference lists of relevant articles. A random-effects or fixed-effects model was used to estimate the sizes of overall and stratification effects of the MTHFR 677C/T polymorphism on the risk of DR, as appropriate. RESULTS: Risks were evaluated by odds ratios (OR) with 95% confidence intervals (95% CI). We found a significant association between the MTHFR 677C/T polymorphism and the risk of DR for each genetic model (recessive model: OR = 1.67; 95% CI: 1.19-2.40 and dominant model: OR = 1.71; 95% CI: 1.28-2.28; respectively). In stratified analysis; we further found that the Asian group with both types of diabetes mellitus (DM) showed a significant association with genetic models (recessive model: OR = 2.16; 95% CI: 1.75-2.60 and dominant model: OR = 1.98; 95% CI: 1.42-2.76; respectively). CONCLUSIONS: Our study suggested that the MTHFR 677C/T polymorphism may contribute to DR development, especially in Asian populations. Prospective and additional genome-wide association studies (GWAS) are needed to clarify the real role of the MTHFR gene in determining susceptibility to DR.

Nested Case-control Study of Occupational Radiation Exposure and Breast and Esophagus Cancer Risk among Medical Diagnostic X Ray Workers in Jiangsu of China.

Medical diagnostic X-ray workers are one occupational group that expose to the long-term low-dose external radiation over their working lifetime, and they may under risk of different cancers. This study aims to determine the relationship between the occupational X-ray radiation exposure and cancer risk among these workers in Jiangsu, China. We conducted Nested case-control study to investigate the occupational X-ray radiation exposure and cancer risk. Data were collected through self-administered questionnaire, which includes but not limits to demographic data, personal behaviors and family history of cancer. Retrospective dose reconstruction was conducted to estimate the cumulative doses of the x-ray workers. Inferential statistics, t-test and 2 tests were used to compare the differences between each group. We used the logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of cancer by adjusting the age, gender. All 34 breast cancer cases and 45 esophageal cancer cases that detected in a cohort conducted among health workers between 1950~2011 were included in this presented study, and 158 cancer-free controls were selected by frequency-matched (1:2). Our study found that the occupational radiation exposure was associated with a significantly increased cancer risk compared with the control, especially in breast cancer and esophageal cancer (adjusted OR=2.90, 95% CI: 1.19-7.04 for breast cancer; OR=4.19, 95% CI: 1.87-9.38 for esophageal cancer, and OR=3.43, 95% CI: 1.92-6.12 for total cancer, respectively). The occupational X-ray radiation exposure was associated with increasing cancer risk, which indicates that proper intervention and prevention strategies may be needed in order to bring down the occupational cancer risk.

Knowledge of and attitude to nuclear power among residents around Tianwan Nuclear Power Plant in Jiangsu of China.

AIMS: The aims of this paper were to determine the level of knowledge of and attitude to nuclear power among residents around Tianwan Nuclear power plant in Jiangsu of China. DESIGN: A descriptive, cross-sectional design was adopted. PARTICIPANTS: 1,616 eligible participants who lived around the Tianwan nuclear power plant within a radius of 30km and at least 18 years old were recruited into our study and accepted epidemiological survey. METHODS: Data were collected through self-administered questionnaires consisting of a socio-demographic sheet. Inferential statistics, t-test, ANOVA test and multivariate regression analysis were used to compare the differences between each subgroup and correlation analysis was conducted to understand the relationship between different factors and dependent variables. RESULTS: Our investigation found that the level of awareness and acceptance of nuclear power was generally not high. Respondents' gender, age, marital status, residence, educational level, family income and the distance away from the nuclear power plant are important effect factors to the knowledge of and attitude to nuclear power. CONCLUSIONS: The public concerns about nuclear energy's impact are widespread. The level of awareness and acceptance of nuclear power needs to be improved urgently.

Association between two genetic polymorphisms of the renin-angiotensin-aldosterone system and diabetic nephropathy: a meta-analysis.

The widely studied candidate genes of the renin-angiotensin-aldosterone system, angiotensinogen (AGT), and angiotensin II receptor type 1 (AGTR1), are implicated in the development of diabetic nephropathy (DN). A number of studies have evaluated the association between the functional polymorphisms, AGT M235T and AGTR1 A1166C, and DN risk with conflicting results. The present meta-analysis was performed to estimate the overall risk of these polymorphisms associated with DN on 4,377 DN cases and 4,905 controls from 34 published case-control studies by searching electronic databases and reference lists of relevant articles. We examined the association between each polymorphism and the risk of DN by odds ratio (OR) with 95% confidence intervals (95% CI) and calculated the ORs for different genetic model. In addition, stratification analysis by ethnicity and diabetes mellitus (DM) type was conducted. In this meta-analysis, we failed to find any significant main effects in both overall analysis and stratified analysis for the AGT M235T. However, the overall analysis detected a significant association between the AGTR1 A1166C and the risk of DN for the CC compared with the AA and dominant genetic model (CC vs. AA: OR = 2.10, 95% CI: 1.00-4.44; dominant model: OR = 2.11, 95% CI: 1.06-4.23). In subgroup analysis, only patients with T2DM showed significant association for CC vs. AA model and dominant model (CC vs. AA: OR = 3.31, 95% CI: 1.21-9.08; dominant model: OR = 3.50, 95% CI: 1.41-8.69). This study suggests that the AGTR1 A1166C polymorphism may contribute to DN development, particularly in T2DM patients.

Common BRCA1 and BRCA2 mutations in breast cancer families: a meta-analysis from systematic review.

A number of molecular epidemiological studies have been conducted the screening for BRCA1 and BRCA2 mutations in breast cancer patients with a positive family history of breast and/or ovarian cancer and reported many common mutations in BRCA1 and BRCA2 associated in breast cancer in different population and different ethnicity. However, it's still lack of a systematic analysis on these mutations. To comprehensively evaluate the frequency and distribution of common BRCA1 and BRCA2 mutations which associated with breast cancer risk, we address this issue through system review and meta-analysis on 29 relevant published studies by conducting a literature search on PubMed and CNKI. 20 common founder germline mutations were identified from all 29 studies and 4 of BRCA1 (5382insC, 185delAG, 3819del5 and 4153delA) and 2 of BRCA2 (4075delGT, 5802del4) mutations were repeatedly reported twice or more in different articles, respectively. For the BRCA1, after conducting meta-analysis, we found that the overall frequency of 5382insC was 0.09 (95% CI 0.06-0.12), the frequency of 185delAG was 0.07 (95% CI 0.01-0.13), the frequency of 3819del5 was 0.02 (95% CI 0.01-0.04) and the frequency of 4153delA was 0.06 (95% CI 0.03-0.09). For the BRCA2, the overall frequency of 4075delGT was 0.02 (95% CI 0.00-0.03) and the frequency of 5802del4 was 0.07 (95% CI 0.04-0.11). This article provides a set of common mutations for BRCA1 and BRCA2 mutation carriers and the results may help to explore frequencies of BRCA1 and BRCA2 mutations in a given population and will be of significance both for diagnostic testing and for epidemiological studies.

Association between genetic polymorphism of the angiotensin-converting enzyme and diabetic nephropathy: a meta-analysis comprising 26,580 subjects.

INTRODUCTION: The effect of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on risk of diabetic nephropathy (DN) is still conflicting. The present meta-analysis was performed to evaluate the overall risk of this polymorphism associated with DN in different groups. MATERIALS AND METHODS: A predefined search was performed on 14,108 DN cases and 12,472 controls from 63 published studies by searching electronic databases and reference lists of relevant articles. RESULTS: In this meta-analysis, we found a significant association between the ACE I/D polymorphism and the risk of DN for all genetic models (ID versus II: odds ratio [OR] = 1.12, 95% confidence interval [CI] 1.02-1.24; DD versus II: OR = 1.27, 95% CI 1.13-1.44; allele contrast: OR = 1.15, 95% CI 1.08-1.23; dominant model: OR = 1.18, 95% CI 1.07-1.31; and recessive model: OR = 1.18, 95% CI 1.08-1.30, respectively). In stratified analysis by ethnicity and DM type, we further found that the Asian group with type 2 diabetes mellitus (T2DM) showed a significant association for all genetic models (ID versus II: OR = 1.25, 95% CI 1.07-1.47; DD versus II: OR = 1.57, 95% CI 1.24-1.98; allele contrast: OR = 1.30, 95% CI 1.15-1.46; dominant model: OR = 1.37, 95% CI 1.10-1.69; and recessive model: OR = 1.34, 95% CI 1.15-1.56, respectively). CONCLUSIONS: Our study suggested that the ACE I/D polymorphism may contribute to DN development, especially in the Asian group with T2DM.

Replication and functional genomic analyses of the breast cancer susceptibility locus at 6q25.1 generalize its importance in women of chinese, Japanese, and European ancestry.

We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.30 (1.22-1.38) and 1.64 (1.50-1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10⁻³°], Japanese women [ORs (95% CI) = 1.31 (1.13-1.52) and 1.37 (1.06-1.76), P for trend = 2.51 × 10⁻4], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99-1.16) and 1.18 (1.04-1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63-1.06) and 0.85 (0.65-1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r(2) = 0.91) and European-ancestry (r² = 0.83) populations, but not in Africans (r² = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region.

A variant affecting miRNAs binding in the circadian gene Neuronal PAS domain protein 2 (NPAS2) is not associated with breast cancer risk.

Disruption of the circadian rhythm has been reported to increase the risk of breast cancer. A single nucleotide polymorphism (SNP) rs2305160 in Neuronal PAS domain protein 2 (NPAS2), the largest circadian gene, was identified as a breast cancer susceptibility locus. In the current study, we found a novel functional SNP (rs3739008) located at 3'UTR of NPAS2 and the C to T changing of the SNP may disrupt the binding of microRNA- (miR-) 17-5p and miR-519e to the 3'UTR of NPAS2. We then typed this SNP in case-control studies of both Chinese and Germany populations to test its putative associations with breast cancer risk. However, we failed to find any significant associations by different genetic models (dominant genetic model, adjusted OR = 1.13, 95% CI = 0.95-1.35 for the Chinese population and adjusted OR = 0.99, 95% CI = 0.85-1.16 for the Germany population). Although we did not find significant associations at population levels from both Chinese and Germany case-control studies, due to the functional relevance of rs3739008 on NASP2 expression, it will be promising to investigate the influence of this variant on clinical characteristics of breast cancer and breast cancer survival.

Genetic polymorphism of p53, but not GSTP1, is association with susceptibility to esophageal cancer risk - a meta-analysis.

A number of studies have evaluated two functional polymorphisms on p53 Arg72Pro and GSTP1 Ile105Val, in relation to esophageal cancer susceptibility. However, the results remain conflicting rather than conclusive. This meta-analysis on 2919 cases and 4074 controls for p53 Arg72Pro and 1885 cases and 2194 controls for GSTP1 Ile105Val from 13 published case-control studies showed that no significant general main effects for GSTP1 Ile105Val on esophageal cancer risk. However, we found that the p53 Arg72Pro was associated with an increased risk of esophageal cancer ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.20, 95%CI=1.06-1.36) without any between-study heterogeneity. In the stratified analysis by ethnicity, we found that the increased esophageal cancer risk associated with p53 Arg72Pro polymorphism was more evident in Asian group ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.35, 95%CI=1.14-1.60, P=0.09 for heterogeneity test), although we still failed to find any significant association between GSTP1 Ile105Val polymorphism and esophageal cancer risk in different ethnicity. These results suggest that p53 Arg72Pro polymorphism, but not GSTP1 Ile105Val, may contribute to esophageal cancer development, especially in Asian. Additional well-designed large studies were required for the validation of this association.

Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium.

Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20-1.31) per allele (P = 3.2 x 10(-25)) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR = 1.19, 95% CI = 1.09-1.31, P = 1.3 x 10(-4), 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures.

[Relationship between polymorphisms of X-ray repair cross-complementing group 1 gene Arg194Trp, Arg399Gln and susceptibility of breast cancer].

OBJECTIVE: To study the relationship between two polymorphisms, Arg194Trp and Arg399Glu, of DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) and the susceptibility of breast cancer in Chinese women. METHODS: A case-control study with 698 histologically-confirmed female breast cancer cases and 813 cancer-free controls frequency-matched by age and residential area was conducted, and the genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. Logistic regression analysis was used to evaluate the odds ratios (ORs) and 95% confidence intervals (CIs) of XRCC1 Arg194Trp and Arg399Glu with susceptibility of breast cancer. A Meta-analysis was used to evaluate the association of Arg399Glu with breast cancer in Chinese women. RESULTS: The genotype frequencies of Arg/Arg, Arg/Trp, Trp/Trp, Arg/Trp + Trp/Trp of XRCC1 gene 194 locus were 48.81% (327/670), 39.85% (267/670), 11.34% (76/670), 51.19% (343/670) in cases and 48.80% (387/793), 41.99% (333/793), 9.21% (73/793), 51.20% (406/793) in controls. Compared to Arg/Arg, the adjusted ORs (95%CIs) were 0.98 (0.75 - 1.28), 1.17 (0.76 - 1.80), 1.09 (0.86 - 1.40). The frequencies of Arg/Arg, Arg/Trp, Trp/Trp, Arg/Gln + Gln/Gln of XRCC1 399 locus were 52.40% (349/666), 38.29% (255/666), 9.31%(62/666), 47.60% (317/666) in cases and 52.22% (412/789), 38.53% (304/789), 9.25% (73/789), 47.78%(377/789) in controls. Compared to Arg/Arg, the adjusted ORs (95%CIs) were 0.93(0.63 - 1.08), 0.96 (0.42 - 1.09), 0.91 (0.62 - 1.05). No significant associations were found between these two polymorphisms and breast cancer risk, also in subgroups stratified by menopause status, history of breast-feed, reproduction and taking oral contraceptives. The overall ORs (95%CIs) of 399 Arg/Trp + Trp/Trp vs Arg/Arg from Meta analysis was 0.97 (0.85 - 1.10). CONCLUSION: The XRCC1 Arg194Trp and Arg399Gln may not play an important role in the susceptibility of breast cancer in Chinese women.

Genetic variants in trinucleotide repeat-containing 9 (TNRC9) are associated with risk of estrogen receptor positive breast cancer in a Chinese population.

Trinucleotide repeat-containing 9 (TNRC9), a high mobility group chromatin-associated protein, has been implicated in breast cancer metastasis to the bone. Recently, several single nucleotide polymorphisms (SNPs) of TNRC9 were identified as novel breast cancer susceptibility loci by whole genome association studies, especially in estrogen receptor (ER) positive tumors. In the present case-control study of 1,049 breast cancer patients and 1,073 cancer-free controls in a Chinese population, we genotyped three polymorphisms (rs3803662C/T, rs12443621A/G, and rs8051542C/T) of the TNRC9 gene using the SNPstream 12-plex platform to test the hypothesis that these SNPs are associated with breast cancer risk in this population. None of the three polymorphisms was significantly associated with breast cancer risk in the whole data set (P = 0.151, 0.644, and 0.737 for rs3803662, rs12443621. and rs8051542, respectively). However, rs12443621 AG/GG genotypes were significantly associated with increased risk of ER positive breast cancer (OR = 1.38, 95% CI = 1.01-1.88), compared with homozygote AA. In addition, a borderline significantly increased risk was also observed for the variant genotypes (CT/TT) of rs8051542 C/T compared with the wild-type genotype (CC) (adjusted OR = 1.26, 95% CI = 0.99-1.60). Interestingly, a significant interaction was detected between rs12443621A/G and ER status on breast cancer risk in a case-only analysis (P for interaction = 0.004). These findings suggest that genetic variants of TNRC9 may contribute to the development of ER positive breast cancer.

Association between regulated upon activation, normal T cells expressed and secreted (RANTES) -28C/G polymorphism and asthma risk--a meta-analysis.

Regulated upon activation, normal T-cell expressed and secreted (RANTES) is one of the most extensively studied C-C chemokines in allergic inflammation. A growing body of evidence suggests that many cell types present in asthmatic airways have the capacity to generate RANTES, which directly supported the potential role of RANTES in asthma. A number of studies have evaluated the functional polymorphism -28C/G in the RANTES promoter region, which had been found to affect the transcription of the RANTES gene, in relation to asthma susceptibility. However, the results remain conflicting rather than conclusive. This meta-analysis on 1894 asthma cases and 1766 controls for -28C/G from 9 published case-control studies showed that the variant allele -28G was associated with significantly increased risk of asthma (GG+CG vs CC: OR=1.24, 95%CI=1.08-1.41) without any between-study heterogeneity.In the stratified analysis by asthma type, age and ethnicity, we found that the increased asthma risk associated with -28G/C polymorphism was more evident in children (OR=1.24, 95%CI=1.06-1.45), Asian group (OR=1.27, 95%CI=1.04-1.56) and African group (OR=1.72, 95%CI=1.07-2.78). These results suggest that RANTES -28G/C polymorphism may contribute to asthma development, especially in children and in Asian population. Additional well-designed large studies were required for the validation of this association.

Association between manganese superoxide dismutase (MnSOD) Val-9Ala polymorphism and cancer risk - A meta-analysis.

A growing body of evidence suggests that reactive oxygen species (ROS) play an important role in human cancers. Manganese superoxide dismutase (MnSOD) is the major antioxidant in the mitochondria, catalysing the dismutation of superoxide radicals to form hydrogen peroxide. Since the identification of a well-characterised functional polymorphism, Val-9Ala of MnSOD, a number of molecular epidemiological studies have evaluated the association between Val-9Ala and cancer risk. However, the results remain conflicting rather than conclusive. This meta-analysis on 15,320 cancer cases and 19,534 controls from 34 published case-control studies shows no significant overall main effect of MnSOD Val-9Ala on cancer risk. However, we found that the MnSOD 9Ala allele was associated with an increased prostate cancer risk (Val/Ala versus Val/Val: odds ratio (OR)=1.1; 95% confidence intervals (CI): 1.0-1.3; Ala/Ala versus Val/Val: OR=1.3; 95% CI: 1.0-1.6; Val/Ala+Ala/Ala versus Val/Val: OR=1.2; 95% CI, 1.0-1.3). In addition, we found that the MnSOD Ala-9Ala genotype contributed to an increased breast cancer risk in premenopausal women who had low consumption of antioxidants (Ala/Ala versus Val/Ala+Val/Val: OR=2.6, 95% CI: 1.0-6.4 with low vitamin C consumption; OR=2.1, 95%CI: 1.3-3.4 with low vitamin E consumption and OR=2.9, 95%CI: 1.5-5.7 with low carotenoid consumption). These results suggest that the MnSOD Val-9Ala polymorphism may contribute to cancer development through a disturbed antioxidant balance.

Common genetic variants on 5p15.33 contribute to risk of lung adenocarcinoma in a Chinese population.

Chromosome 5p15.33, containing TERT and CLPTM1L genes, was recently identified as one of the susceptible regions for lung cancer in Caucasian populations. We hypothesized that single-nucleotide polymorphisms (SNPs) identified in this region in Caucasians are also important in the development of lung cancer in Chinese population. To test this hypothesis, we genotyped two most significant SNPs reported in Caucasians, rs2736100A/C and rs402710C/T at 5p15.33, in a case-control study with 1221 non-small cell lung cancer (NSCLC) cases and 1344 cancer-free controls in a Chinese population. We found that rs2736100C allele in TERT gene was associated with a significantly increased risk of NSCLC with adjusted odds ratios of 1.26 [95% confidence interval (CI) = 1.05-1.51] and 1.31 (95% CI = 1.04-1.66) for one or two copies of the variant C allele, respectively. This significant association was more prominent among female (P for heterogeneity: 0.044), non-smokers (P for heterogeneity: 0.054) and/or the subjects with adenocarcinoma (P for heterogeneity: 0.058). However, no significant association was found between rs402710C/T and NSCLC risk. These results suggest that genetic variants in 5p15.33, especially in TERT gene, may also predispose the susceptibility of lung cancer, especially adenocarcinoma, in Chinese population.