Circular RNA hsa_circ_0098181 inhibits metastasis in hepatocellular carcinoma by activating the Hippo signaling pathway via interaction with eEF2.

INTRODUCTION AND OBJECTIVES: The development of hepatocellular carcinoma (HCC) is a multi-step process that accumulates genetic and epigenetic alterations, including changes in circular RNA (circRNA). This study aimed to understand the alterations in circRNA expression in HCC development and metastasis and to explore the biological functions of circRNA. MATERIALS AND METHODS: Ten pairs of adjacent chronic hepatitis tissues and HCC tissues from patients without venous metastases, and ten HCC tissues from patients with venous metastases were analyzed using human circRNA microarrays. Differentially expressed circRNAs were then validated by quantitative real-time PCR. In vitro and in vivo assays were performed to assess the roles of the circRNA in HCC progression. RNA pull-down assay, mass spectrometry analysis, and RNA-binding protein immunoprecipitation were conducted to explore the protein partners of the circRNA. RESULTS: CircRNA microarrays revealed that the expression patterns of circRNAs across the three groups were significantly different. Among these, hsa_circ_0098181 was validated to be lowly expressed and associated with poor prognosis in HCC patients. Ectopic expression of hsa_circ_0098181 delayed HCC metastasis in vitro and in vivo. Mechanistically, hsa_circ_0098181 sequestered eukaryotic translation elongation factor 2 (eEF2) and dissociated eEF2 from filamentous actin (F-actin) to prevent F-actin formation, which blocked activation of the Hippo signaling pathway. In addition, the RNA binding protein Quaking-5 bound directly to hsa_circ_0098181 and induced its biogenesis. CONCLUSIONS: Our study reveals changes in circRNA expression from chronic hepatitis, primary HCC, to metastatic HCC. Further, the QKI5-hsa_circ_0098181-eEF2-Hippo signaling pathway exerts a regulatory role in HCC.

Burden and trend of ischemic heart disease and colorectal cancer attributable to a diet low in fiber in China, 1990-2017: findings from the Global Burden of Disease Study 2017.

PURPOSE: The burden of non-communicable diseases (NCDs) has increased in China. However, the contribution of dietary risks to the NCD burden has not been evaluated. This study aimed to estimate the burden of ischemic heart disease (IHD) and colorectal cancer (CRC) attributable to a diet low in fiber in China from 1990 to 2017. METHODS: China data from the Global Burden of Disease Study (GBD) 2017 were used to assess the age-, sex-, and province-specific mortality and disability-adjusted life-years (DALYs) of IHD and CRC related to a diet low in fiber. RESULTS: In 2017, a diet low in fiber contributed 170,143 [95% uncertainty interval (UI): 99,623-256,806] IHD deaths and 25,561 (95% UI: 13,726-39,215) CRC deaths, with the population attributable fractions (PAFs) were 9.7 and 13.7%, respectively. Males had higher risk-attributable mortality and DALY rates for IHD and CRC than females. An upward trend with age in rates of mortality and DALY was observed. All-age risk-attributable mortality and DALY rates increased significantly by 111.4 and 53.2% for IHD, and 94.4 and 59.6% for CRC from 1990 to 2017, respectively; however, the corresponding age-standardized rates for IHD and CRC showed relatively stable trends. Heilongjiang, Xinjiang, and Inner Mongolia were ranked as the top three provinces in terms of total risk-attributable NCD burden in 2017. CONCLUSIONS: China has a large and growing NCD burden attributable to a diet low in fiber. Greater priority in disease prevention and control should be given to male and older adults throughout China, particularly in some western provinces.

Burden of viral hepatitis caused by specific aetiologies in China, 1990-2016: findings from the GBD 2016.

BACKGROUND: The aim of this study is to quantify the burden caused by viral hepatitis in China from 1990 to 2016. METHODS: Data from the GBD 2016 study were extracted to calculate incidence, prevalence and disability-adjusted life years (DALYs). Trends in DALYs were assessed in 33 provinces/regions. RESULTS: From 1990 to 2016, the total incidence of hepatitis decreased by 88.5%. However, the prevalence of hepatitis (counts in thousands), increased by 37.6% from 153,856 (95% UI: 136,047-172,319) in 1990 to 211,721 (95% UI: 179,776-240,981) in 2016, with age-standardized prevalence rates changing slightly. The number and age-standardized rates of prevalence increased by 35.9 and 1.6% for hepatitis B, respectively, and by 81.8 and 30.4% for hepatitis C. Guangxi, Guangdong and Hainan had the highest age-standardized prevalence rates (≥16,500 per 100,000). Tibet, Qinghai and Gansu had the highest age-standardized DALYs rates (≥40 per 100,000). The largest absolute number of DALYs was observed in the 15-49 year age group in 2016. The highest rate of DALYs occurred in males aged 50-69 years and in females aged ≧70 years. CONCLUSION: The incidence and DALYs of viral hepatitis decreased dramatically from 1990 to 2016. However, the prevalence still remains at a high level, which may result in heavy burdens in the future.

Comprehensive investigating of cytokine and receptor related genes variants in patients with chronic hepatitis B virus infection.

BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is a global health problem and the outcome are associated with both viral factors and host genetic factors. High Throughput Sequencing (HTS) technology were used to identify variants associated with liver disease. METHODS: Fifty-five Chronic hepatitis B (CHB) patients, fifty-three self-healing HBV (SH) patients and 53 healthy controls (HC) were recruited, 404 cytokine and cytokine receptor related genes were captured and sequenced at high depth (>900X), both variant (Fischer's exact test, P value < 0.05) and gene (SKAT-O gene level test, adjust P value < 0.05) level association were used to identify variants and genes associated with CHB. RESULTS: Total 5083 variants have been detected, fifty-four variants were found associated with CHB, most (29/32) variants were located in HLA region, including HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DQB2, HLA-DRB1 and HLA-DRB5. Several missense variants were found associated with CHB, including p.E226K in PVR (poliovirus receptor), p.E400A and p.C431R in IL4R (interleukin 4 receptor). Four variants located in 3'UTR (untranslated region) have also been found associated with CHB. CONCLUSION: Our study revealed that high through target region sequencing, combined with association analysis at variant and gene level, would be a good way to found variants and genes associated with CHB even at small sample size. Our data implied that chronic hepatitis B patients who carry these variants need intensive monitoring.

Decreased frequency of circulating Th9 cells in patients with chronic hepatitis B infection.

BACKGROUND: Chronic hepatitis B (CHB) is one of the major infectious diseases in which CD4+ T helper (Th) cells play a crucial role. Th9 cells are a distinct subset of CD4+ Th cells with important physiological functions. OBJECTIVE: The study aimed to assess the potential involvement of Th9 cells in the inadequate immune response leading to chronic HBV infection. PATIENTS AND METHODS: Peripheral blood samples were collected from 22 CHB patients and 16 healthy controls (HC). The frequencies of circulating Th9, Tc9, Th1, and Tc1 cells were determined by flow cytometry. Serum levels of IL-9 and IL-10 were analyzed by ELISA. Serum biochemical indices of liver function were measured using an automated analyzers. Serum HBV DNA loads were analyzed by real-time PCR. The potential association of the frequency of Th9, Tc9, Th1 or Tc1 cells with clinical parameters was assessed. RESULTS: The frequency of circulating Th9 cells was significantly lower in CHB patients than those in HC. However, no significant differences in the frequency of Tc9, Th1 or Tc1 cells were observed between the two groups. The percentages of Th9 cells, but not Tc9 cells, were negatively correlated with HBV DNA loads, whereas the percentages of Tc1 cells were positively correlated with viral loads in CHB patients. Moreover, there was a positive correlation between serum levels of IL-9 and IL-10 and HBV DNA loads in patients with chronic HBV infection. CONCLUSION: The depletion of Th9 cells is associated with the development of chronic HBV infection.

Association between PNPLA3 gene polymorphisms and risk of hepatitis B virus-related hepatocellular carcinoma in Han population in China:a case-control study.

BACKGROUND AND AIM: Several recent studies showed that the genetic polymorphisms in the PNPLA3 region (rs738408, rs738409, rs2294918, rs2294919 and rs2281135) were with related to various kinds of liver diseases. We analyzed the five single-nucleotide polymorphisms (SNPs) for major HBV outcomes in Han Chinese. METHODS: A total of 2410 samples were involved and peripheral blood samples were collected in this study. The SNPs in the PNPLA3 region were genotyped by using Matrix-assisted laser desorption/ionization time of flight mass spectrometry. RESULTS: Our study indicated the clear relationship between the PNPLA3 rs2294918, rs2294919 and HBV-related HCC after control for the effects of sex, drinking and smoking. Health subjects with the PNPLA3 rs2294919 TC genotype would have a 0.605 (95% CI: 0.413, 0.886; p = .010) times lower odds of having HCC, and those with the rs2294918 AG genotype would have a 1.872 (95% CI: 1.256, 2.792; p = .002) times higher odds of having HCC, whereas the values of sex, age, drinking and smoking were fixed. In addition, CA haplotype of the haplotype block of rs738409 and rs2281135 was also associated with HBV-related HCC. CONCLUSIONS: Our study suggested that PNPLA3 loci (rs2294918, rs2294919) were associated with HBV-related HCC in Han Chinese.

Prevalence of abdominal obesity among Chinese adults in 2011.

BACKGROUND: The prevalence of abdominal obesity is increasing dramatically worldwide. This study aimed to estimate the current prevalence of abdominal obesity from the 2011 China Health and Nutrition Survey (CHNS) and compare the data with other countries. METHODS: Waist circumference (WC) of 12,326 Chinese adults (aged 20 years or older) from the 2011 CHNS were analyzed by age group and region. Abdominal obesity was defined as a WC ≥90 cm for men and WC ≥80 cm for women based on World Health Organization (WHO) recommendations for Asians. RESULTS: In 2011, the age-adjusted mean WC was 85.9 cm (95% confidence interval [CI], 85.6-86.2 cm) for men and 80.7 cm (95% CI, 80.4-80.9 cm) for women. Based on the WHO recommendations, the age-adjusted prevalence of abdominal obesity was 44.0% (95% CI, 43.1%-44.8%) overall, 35.3% (95% CI, 34.1%-36.6%) in men, and 51.7% (95% CI, 50.5%-52.9%) in women. Moreover, the age-adjusted prevalence was 44.0% (95% CI, 42.7%-45.2%) in rural populations, 42.5% (95% CI, 40.7%-44.2%) in urban populations, and 45.2% (95% CI, 43.5%-46.9%) in megacity populations. The prevalence in China (35.3% for men and 51.7% for women) was lower than in Japan (50.8% for men) and the United States (43.5% for men and 64.7% for women). Similar results were observed when applying the criteria suggested by the Working Group on Obesity in China. CONCLUSIONS: In 2011, the age-adjusted prevalence of abdominal obesity in China was 35.3% in men and 51.7% in women.

Genetic polymorphism of HLA-DQ confers susceptibility to hepatitis B virus-related hepatocellular carcinoma: a case-control study in Han population in China.

Several recent genome-wide studies showed that the genetic polymorphisms in the HLA-DQ region (rs9275572 and rs2856718) were related to chronic hepatitis B virus (HBV) infection and chronic hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). We analyzed the two single-nucleotide polymorphisms for major HBV outcomes in Han Chinese. A total of 1291 samples were involved and peripheral blood samples were collected in this study. Matrix-assisted laser desorption/ionization time of flight mass spectrometry were used to genotype the single-nucleotide polymorphisms in the HLA-DQ region. Our study indicated the clear relationship between the HLA-DQ rs9275572 and HBV-related HCC after control for the effects of sex, drinking, and smoking. Health subjects with the HLA-DQ rs9275572 GA genotype would have a 0.641 (95 % CI 0.416, 0.985; P = 0.043) times lower odds of having HCC, and those with the AA genotype would have a 0.256 (95 % CI 0.106, 0.618; P = 0.002) times lower odds of having HCC, whereas the values of the other covariates were fixed. Whereas there was no significant difference found for the HLA-DQ rs2856718 AG and GG genotype. Our study suggested that HLA-DQ loci (rs9275572) were associated with HBV-related HCC as a protective factor in Han Chinese.

Excess Body Weight during Childhood and Adolescence Is Associated with the Risk of Multiple Sclerosis: A Meta-Analysis.

BACKGROUND AND AIM: Several epidemiological studies have reported the association between obesity and multiple sclerosis (MS). METHODS: A literature search of the observational studies, published as original articles in English before December 2015, was performed using electronic databases. RESULTS: Five observational studies were included, of which 3 were case-control studies and 2 were cohort studies. The pooled relative risk (RR) for overweight and obesity during childhood and adolescence compared with normal weight (body mass index = 18.5-24.9 kg/m2) was 1.44 (95% CI 1.22-1.70) and 2.01 (95% CI 1.63-2.48), respectively. In subgroup analyses, we found that excess body weight during childhood and adolescence increased the risk of MS in the female group (overweight: pooled RR = 1.62, 95% CI 1.35-1.94; obesity: pooled RR = 2.25, 95% CI 1.77-2.85), but not in the male group (overweight: pooled RR = 1.19, 95% CI 0.91-1.55; obesity: pooled RR = 1.22, 95% CI 0.79-1.90). CONCLUSIONS: Excess body weight during childhood and adolescence was associated with an increased risk of MS; severe obesity demonstrated a stronger risk. A statistically significant association was found in the female group, but not in the male group.

Joint effects of age and body mass index on the incidence of hypertension subtypes in the China Health and Nutrition Survey: A cohort study over 22years.

OBJECTIVES: We seek to investigate the joint effects of age and body mass index (BMI) on the incident hypertension subtypes among Chinese adults during 1989-2011. METHODS: We investigated the Incidence rates (IRs, per 100person-years) of hypertension subtypes, adjusted relative risks (RRs) and population attributable risk percent (PAR%) of BMI for hypertension, and clarified the age-specific effect of BMI on incident hypertension utilizing a dynamic cohort study from the China Health and Nutrition Survey (CHNS) 1989-2011. RESULTS: Normotensive participants (n=53,028) at baseline were included, with mean age was 41.7 (95% CI, 41.6-41.7)years old. During a total of 118,694person years (average was 6.38years) of follow-up, a total of 5208 incident cases of hypertension were documented. The IRs of hypertension were 4.4 (95% CI, 4.3-4.5), which increased gradually by age and BMI (Ptrend<0.001). Compared with those with BMI<22kg/m(2), the RR of hypertension was 3.13 (95% CI, 2.84-3.45) in the group with BMI≥28kg/m(2). The PAR% (BMI>22 vs. BMI<22) for hypertension in Chinese population was 32% (95% CI, 29-34%). Similar trends were observed in all age and BMI groups for both isolated systolic hypertension and systolic-diastolic hypertension, which were mainly affected by age. In contrast, the peak IR of isolated diastolic hypertension was observed in participants aged 30-49years with higher BMIs. CONCLUSIONS: The PAR% (IR of BP≥140/90 or treatment for BMI>22 vs. IR for BMI<22) of elevated body weight for hypertension was 32% in Chinese population.

A functional polymorphism in microRNA-196a2 is associated with increased susceptibility to non-Hodgkin lymphoma.

Aberrant expression and structural alterations of microRNAs (miRNAs) play important roles in tumorigenesis. The miRNA-196a2 polymorphism is associated with tumorigenesis, but its association with non-Hodgkin lymphoma (NHL) remains unexplored. We evaluated the association between the miRNA-196a2 T>C polymorphism (rs11614913) and NHL risk in a case-control study of 318 NHL cases and 320 healthy controls. We also examined miRNA-196a expression in tissue samples from NHL patients (n = 59). The TC and CC genotypes were associated with cancer risk in NHL [odds ratio (OR) = 1.384, confidence interval (CI) = 1.010-1.898 for TC vs. TT, and OR = 1.822, 95 % CI = 1.163-2.853 for CC vs. TT]. Analysis of the association between this polymorphism and the clinicopathology of NHL showed that the combined TC/CC genotypes were associated with Ann Arbor stage (OR = 1.852, 95 % CI = 1.139-3.010), bone marrow invasion (OR = 1.850, 95 % CI = 1.062-3.223), and B symptoms (OR = 1.852, 95 % CI = .154-2.972), but not with immunohistological subtype, lymph node size, age, or gender. In addition, the CC or CC/TC genotypes were associated with significantly higher levels of mature miR-196a (p = 0.002 or 0.008) in a genotype-phenotype correlation analysis. Our findings suggest that the miR-196a2 polymorphism may increase the risk of NHL by altering the expression of mature miR-196a.

Correlation between polymorphisms in DNA mismatch repair genes and the risk of primary hepatocellular carcinoma for the Han population in northern China.

PURPOSE: This study investigated correlations between polymorphisms in DNA mismatch repair (MMR) genes and the risk of primary hepatocellular carcinoma (PHC). METHODS: Single nucleotide polymorphisms (SNPs) in the DNA MMR genes MLH3 (rs175080), PMS1 (rs5742933), PMS2 (rs1059060), MSH3 (rs26279), MSH5 (rs1150793, rs2075789) and MSH6 (rs1042821) were detected using the SNaPshot method in 250 PHC cases and in 308 patients without PHC in the Han population in northern China. RESULTS: The AA genotype in MLH3 (rs175080) increased the risk of PHC (odds ratio [OR] = 3.424; 95% confidence interval [CI]: 1.097-10.689). The AG and GG genotypes in MSH3 (rs26279) increased the risk of PHC (OR: 1.644 and 3.300; 95% CI: 1.112-2.428 and 1.765-6.168, respectively). The AA genotype in MSH5 (rs2075789) increased the risk of PHC (OR: 9.229; 95% CI: 1.174-72.535). The CT genotype in MSH6 (rs1042821) reduced the risk of PHC (OR: 0.629; 95% CI: 0.428-0.924). CONCLUSIONS: Our study suggests that polymorphisms in MLH3 (rs175080), MSH3 (rs26279), MSH5 (rs2075789) and MSH6 (rs1042821) may be independent risk factors for PHC.

The association between overweight, obesity and ovarian cancer: a meta-analysis.

OBJECTIVE: Epidemiological studies have reported an inconsistent association between obesity and ovarian cancer. To update the current knowledge of and further qualify the association between overweight, obesity and ovarian cancer risk, we conducted a meta-analysis of published observational studies. METHODS: Using the PubMed, MEDLINE and EMBASE databases, we performed a literature search of all of the case-control and cohort studies published as original articles in English before March 2015. We included 26 observational studies, of which 13 were case-control studies (7782 cases and 21 854 controls) and 13 were cohort studies (5181 cases). Fixed- and random-effects models were used to compute summary estimates and the corresponding 95% confidence intervals. Subgroup analyses were also performed. RESULTS: The pooled relative risk for overweight and obesity compared with normal weight (body mass index = 18.5-24.9 kg/m(2)) was 1.07 (95% confidence interval: 1.02-1.12) and 1.28 (95% confidence interval: 1.16-1.41), respectively. In subgroup analyses, we found that overweight/obesity increased the risk of ovarian cancer in most groups, except for the postmenopausal group (overweight: pooled relative risk = 0.97, 95% confidence interval: 0.76-1.24; obesity: pooled relative risk = 0.93, 95% confidence interval: 0.61-1.42). There was no evidence of publication bias. CONCLUSIONS: Increased body weight was associated with an increased risk of ovarian cancer; in particular, severe obesity demonstrated a stronger risk effect. No statistically significant association was observed in the postmenopausal period, but was in the premenopausal period.

Mortality analysis on wastewater exposure in Shijiazhuang, Hebei, China, from 2007 to 2011.

The study investigated the age-adjusted mortality rate and disease odds among deceased residents living in areas exposed to wastewater and cleanwater from 2007 to 2011, in Shijiazhuang, China. Mortality data for eight villages exposed to wastewater and 16 villages not exposed to wastewater were collected and crosschecked from multiple sources. Overall mean age-adjusted mortality rate for wastewater areas was 798/105 (95% Confidence Interval (CI) = ± 68), insignificantly higher than the mean mortality rate for cleanwater area, 726/105 (95% CI = ± 46), p > 0.05. Malignant neoplasms and respiratory mortality and disease odds were higher in wastewater areas than in cleanwater areas, OR = 1.7 (95% CI = 1.3-2.2, p < 0.01) and OR = 1.9 (95% CI = 1.1-3.4, p < 0.05), respectively. Wastewater area mortality and disease odds for Lung and Stomach cancers after adjustments were OR = 1.6 (95% CI = 1.1-2.4, p < 0.05) and OR = 1.8 (95% CI = 1.2-2.7, p < 0.01), respectively, significantly higher than those of cleanwater areas. There is a possibility that exposure to wastewater might be associated with cancer and respiratory disease mortality. The study recommends that the use of wastewater be limited, discouraged, or discontinued.

Alpha-synuclein (SNCA) polymorphisms and susceptibility to Parkinson's disease: a meta-analysis.

It has been reported that single nucleotide polymorphisms (SNPs) of Alpha-synuclein (SNCA) are associated with Parkinson's disease (PD). Some researchers have attempted to validate this finding in various ethnic populations. The results of studies concerning SNCA polymorphisms and PD susceptibility remain conflicting. To evaluate the association between these SNPs and PD, the authors conducted a series of meta-analyses using a predefined protocol. Databases including PubMed, MEDLINE and PD gene were searched to identify relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. All analyses were calculated using STATA11.0. A total of 19 studies on the SNPS rs181489, rs356186, rs356219, rs894278, rs2583988, rs2619363, rs2619364, rs2737029, rs10005233 and rs11931074 were included. This meta-analysis showed that eight out of these 10 candidate SNPs may be associated with PD risk. Significant association was found between PD and the following SNPs: rs181489, rs356186, rs356219, rs894278 rs2583988, rs2619364, rs10005233 and rs11931074. Among these SNPs, rs356186 was found to be the only SNP that may play a protective role in Parkinson's disease. These results suggest that the SNCA gene may be associated with PD.

Null genotype of GSTT1 contributes to increased Parkinson's disease risk in Caucasians: evidence from a meta-analysis.

Conflicting results in previous case-control studies on the association between Glutathione S-transferase T1 (GSTT1) gene polymorphism and Parkinson's disease (PD) risk have been reported, so we conducted this meta-analysis. We searched and extracted data from 3 Chinese and 3 English web-based electronic databases to evaluate the associations by odds ratio (OR) and its 95% confidence interval (CI) under the recessive genetic comparison model (null genotype vs. present genotype). We also conducted subgroup analyses by ethnicity and adjusted status of OR, respectively. Meta-analyses and subgroup analyses of larger studies (sample size ≥300) were also reanalyzed. When 18 eligible studies (3,963 PD cases and 5,472 controls) were pooled to analyze the association, we found no statistically significant result (OR 1.24, 95% CI 0.96-1.60). In the subgroup analyses by ethnicity, there was statistically significant association between the null genotype of GSTT1 and PD risk among Caucasians, while the associations were not found among Asians and Latinos. In the subgroup analyses by adjusted status of OR, there were no significant associations both in studies with crude OR and adjusted OR. Meta-analyses and subgroup analyses of larger studies (sample size ≥300) were also confirmed the associations mentioned above. Power analysis indicated only meta-analysis of Caucasians had enough evidence to claim the association. In conclusion, the meta-analysis suggests that the null genotype of GSTT1 contributes to PD risk in Caucasians, and no association in Asians is needed more studies to confirm.

Serum 25-hydroxyvitamin D and breast cancer risk: a meta-analysis of prospective studies.

There were some case-control studies, nested case-control studies, and cohort studies with controversial results on the association between serum 25-hydroxyvitamin D [25(OH)D] and breast cancer risk. Case-control studies are prone to selection bias, which limit the strength and quality of the evidence. To overcome the shortcoming of the case-control studies, the meta-analysis of prospective studies including nested case-control studies and cohort studies was conducted. PubMed, Embase, and Web of Science databases were searched, and the last retrieval date was March 24, 2013. For the highest versus the lowest level of serum 25(OH)D, the relative risks (RRs) and its 95% confidence intervals (CIs) from each study were used to estimate summary RR and its 95% CI. Subgroup analyses by geographic region, menopausal status, and adjusted status of RR were also performed, respectively. A dose-response association between serum 25(OH)D concentration and breast cancer risk was assessed. Fourteen articles with 9,110 breast cancer cases and 16,244 controls were included in the meta-analysis. Overall, serum 25(OH)D levels were inversely significantly associated with breast cancer risk (RR = 0.845, 95% CI = 0.750-0.951). Inversely statistically significant associations were observed in North American studies, postmenopausal women, and studies with adjusted and unadjusted RR, respectively. No statistically significant associations were observed in European studies and premenopausal women, respectively. Dose-response analysis showed that every 10 ng/mL increment in serum 25(OH)D concentration was associated with a significant 3.2% reduction in breast cancer risk. This meta-analysis provides evidence of a significantly inverse association between serum 25(OH)D concentration and breast cancer risk.

Functional variants in NBS1 and cancer risk: evidence from a meta-analysis of 60 publications with 111 individual studies.

Several potentially functional variants of Nijmegen breakage syndrome 1 (NBS1) have been implicated in cancer risk, but individually studies showed inconclusive results. In this study, a meta-analysis based on 60 publications with a total of 39 731 cancer cases and 64 957 controls was performed. The multivariate method and the model-free method were adopted to determine the best genetic model. It was found that rs2735383 variant genotypes were associated with significantly increased overall risk of cancer under the recessive genetic model [odds ratio (OR) =1.12, 95% confidence interval (CI): 1.02-1.22, P = 0.013]. Similar results were found for rs1063054 under the dominant model effect (OR = 1.12, 95% CI: 1.01-1.23, P = 0.024). The I171V mutation, 657del5 mutation and R215W mutation also contribute to the development of cancer (for I171V, OR = 3.93, 95% CI: 1.68-9.20, P = 0.002; for 657del5, OR = 2.79, 95% CI: 2.17-3.68, P < 0.001; for R215W, OR = 1.77, 95% CI: 1.07-2.91, P = 0.025). From stratification analyses, an effect modification of cancer risks was found in the subgroups of tumour site and ethnicity for rs2735383, whereas the I171V, 657del5 and R215W showed a deleterious effect of cancer susceptibility in the subgroups of tumour site. However, rs1805794, D95N and P266L did not appear to have an effect on cancer risk. These results suggest that rs2735383, rs1063054, I171V, 657del5 and R215W are low-penetrance risk factors for cancer development.

Association between gene polymorphisms of IL-28 and response to lamivudine in Chinese rural patients with chronic hepatitis B.

OBJECTIVE: To assess the association between gene polymorphisms (single nucleotide polymorphisms [SNPs]) of rs8099917 and rs12980602 in the IL-28 gene and the response to lamivudine treatment in naïve of Chinese rural patients. MATERIAL AND METHODS: Three hundred and fifty-four naïve chronic hepatitis B (CHB) patients treated with lamivudine were enrolled in this study. Rs8099917 and rs12980602 SNPs were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Baseline characteristics and genotypes were compared between 181 patients with treatment response and 173 without response. RESULTS: The IL-28 genotypes were independently associated with responses at 1 year post-treatment with lamivudine in CHB patients (OR for rs8099917 GT/GG vs. TT, 4.097 [95% CI, 1.342-12.512; p = 0.015]; OR for rs12980602CT/CC vs. TT, 2.27 [95% CI, 1.202-4.284; p =0.014]). When adjusting for age, gender, smoking, drinking, and levels of hepatitis B virus (HBV) DNA, alanine aminotransferase, and HBV genotype, the rs8099917 genotype GT (OR, 4.025 [95% CI, 1.316-12.354; p = 0.013] and fibrosis stage (OR, 0.716 [95% CI, 0.432-0.986; p = 0.036] appeared to be associated with a higher probability of response to lamivudine treatment. CONCLUSION: The genotype G/T for rs8099917 of IL-28 gene and early fibrosis stage may be predictive of treatment success.

Association of the rs3077 and rs9277535 polymorphisms in HLA-DP with hepatitis B virus infection and spontaneous clearance: a meta-analysis.

PURPOSE: Owing to inconsistent observations in the literature of an association between HLA-DP polymorphisms (rs3077 and rs9277535) and hepatitis B virus (HBV) infection and spontaneous clearance, there is an urgent need for a comprehensive and reliable understanding of this subject. This meta-analysis was performed to quantitatively summarise the evidence for the relevance of these HLA-DP polymorphisms to HBV infection and spontaneous clearance. METHODS: A meta-analysis was conducted with the data from eight relevant papers published from April 2009 to March 2012, following strict selection. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for alleles, co-dominant, dominant and recessive genotype models of the rs3077 and rs9277535 loci. RESULTS: Our analysis indicated a significant association of rs3077 and rs9277535 in HLA-DP with HBV infection, suggesting that these HLA-DP polymorphisms act beneficially against HBV infection (for rs3077, AG vs. GG: OR = 0.522, 95% CI = 0.485-0.561; AA vs. GG: OR = 0.350, 95% CI = 0.311-0.393; for rs9277535, AG vs. GG: OR = 0.542, 95% CI = 0.506-0.579; AA vs. GG: OR = 0.371, 95% CI = 0.336-0.409). Additionally, these HLA-DP polymorphisms served as protective factors in the spontaneous clearance of HBV (for rs3077, AG vs. GG: OR = 0.600, 95% CI = 0.464-0.775; AA vs. GG: OR = 0.420, 95% CI = 0.299-0.590; for rs9277535, AG vs. GG: OR = 0.623, 95% CI = 0.570-0.681 and AA vs. GG: OR = 0.464, 95% CI = 0.386-0.556) with similar results for both dominant and recessive genotype models. CONCLUSIONS: Our results demonstrated that the rs3077 and rs9277535 HLA-DP polymorphisms reduced HBV infection and increased the likelihood of spontaneous viral clearance in some Asian populations.