Serum copper and zinc levels in breast cancer: A meta-analysis

BackgroundMore and more studies have investigated the relationship between serum copper (Cu) and/or zinc (Zn) levels and breast cancer (BC). However, the results are inconsistent. It is unclear whether the serum Cu to Zn ratio (Cu/Zn) is associated with BC risk. Therefore, we evaluated serum Cu and Zn concentrations, and Cu/Zn in BC through meta-analysis.Materials and methodsStudies reporting serum Cu and/or Zn concentrations in BC patients and controls from 1991 to 2020 were identified from PubMed, CNKI, and Wanfang databases online. Based on a random effects model, summary standard mean differences (SMDs) and the corresponding 95 % confidence intervals (95 % CIs) were applied to compare the serum levels of Cu, Zn and Cu/Zn between BC patients and controls.ResultsThirty-six eligible studies involving 5747 female subjects were included. The present study illustrated that the BC patients had significantly higher serum Cu levels than healthy controls (HC) (SMD (95 % CI): 1.99(1.48, 2.49)) and patients with benign breast diseases (BD) (SMD (95 % CI): 0.99(0.38, 1.61)). However, Zn concentrations were statistically decreased in BC patients than HC (SMD (95 % CI): -1.20(-1.74, -0.66)) and BD (SMD (95 % CI): -1.13 (-1.73, -0.54)). Cu/Zn concentrations were remarkably increased in BC patients than HC (SMD (95 % CI): 2.75(1.79, 3.60)) and BD (SMD (95 % CI): 2.98(1.91, 4.05)) in some studies.ConclusionThe results show that elevated serum levels of Cu and Cu/Zn, as well as decreased Zn might be associated with increased risk of breast cancer. These three parameters have the potential to distinguish breast cancer from benign breast diseases.     

Low Serum Levels of Zinc,Copper, and Iron as Risk Factors for Osteoporosis: a Meta-analysis

Zinc (Zn), copper (Cu), and iron (Fe) are essential trace elements for the growth, development, and maintenance of healthy bones. However, there are conflicting reports as to the relationship between serum level of Zn, Cu, or Fe and osteoporosis (OP). The purpose of the present study is to clarify the relationship between serum Zn, Cu, or Fe and OP using a meta-analysis approach. We searched all articles indexed in PubMed published up to May 2014 concerning the association between serum level of Zn, Cu, or Fe and OP. Eight eligible articles involving 2,188 subjects were identified. Overall, pooled analysis indicated that patients with OP had a lower serum level of Zn, Cu, or Fe than the healthy controls (Zn standardized mean difference (SMD)?=??1.396, 95 % confidence interval (CI)?=?[?2.129, ?0.663]; Cu SMD?=??0.386, 95 % CI?=?[?0.538, ?0.234]; Fe SMD?=??0.22, 95 % CI?=?[?0.30, ?0.13]). Further subgroup analysis found that geographical location and gender had an influence on the serum level of Zn in OP and healthy controls, but not on the serum level of Cu or Fe. No evidence of publication bias was observed. In conclusion, this meta-analysis suggests that low serum levels of Zn, Cu, and Fe seem to be important risk factors for OP and well-designed studies with adequate control for confounding factors are required in future investigations.     

Association Between Tumor Necrosis Factor-α and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes: a Meta-Analysis

Tumor necrosis factor-α (TNF-α) is a cell signaling protein involved in systemic inflammation, and is also an important cytokine in the acute phase reaction. Several studies suggested a possible association between TNF-α and diabetic peripheral neuropathy (DPN) in type 2 diabetic patients, but no accurate conclusion was available. A systematic review and meta-analysis of observational studies was performed to comprehensively assess the association between serum TNF-α levels and DPN in type 2 diabetic patients. We searched Pubmed, Web of Science, Embase, and China Biology Medicine (CMB) databases for eligible studies. Study-specific data were combined using meta-analysis. Fourteen studies were finally included into the meta-analysis, which involved a total of 2650 participants. Meta-analysis showed that there were obviously increased serum TNF-α levels in DPN patients compared with type 2 diabetic patients without DPN (standard mean difference [SMD]?=?1.203, 95 % CI 0.795–1.611, P?<?0.001). There were also obviously increased levels of serum TNF-α in diabetic patients with DPN when compared with healthy controls (SMD?=?2.364, 95 % CI 1.333–3.394, P?<?0.001). In addition, there were increased serum TNF-α levels in painful DPN patients compared with painless DPN patients (SMD?=?0.964, 95 % CI 0.237–1.690, P?=?0.009). High level of serum TNF-α was significantly associated with increased risk of DPN in patients with type 2 diabetes (odds ratio [OR]?=?2.594, 95 % CI 1.182–5.500, P?=?0.017). Increased serum levels of TNF-α was not associated with increased risk of painful DPN in patients with type 2 diabetes (OR?=?2.486, 95 % CI 0.672–9.193, P?=?0.172). Sensitivity analysis showed that there was no obvious change in the pooled estimates when omitting single study by turns. Type 2 diabetic patients with peripheral neuropathy have obviously increased serum TNF-α levels than type 2 diabetic patients without peripheral neuropathy and healthy controls, and high level of serum TNF-α may be associated with increased risk of peripheral neuropathy independently. Further prospective cohort studies are needed to assess the association between TNF-α and DPN.     

Association Between Serum Level of Magnesium and Postmenopausal Osteoporosis: A Meta-analysis

There are conflicting reports as to the association between serum level of magnesium (Mg) and postmenopausal osteoporosis (OP). The purpose of the present study is to clarify the association between serum level of Mg and postmenopausal OP using a meta-analysis approach. We searched articles indexed in Pubmed and the Chinese Journal Full-text Database (CJFD) published as of October 2013 that met our predefined criteria. Seven eligible studies involving 1,349 postmenopausal women from 12 case-control study arms were identified. Overall, pooled analysis indicated that postmenopausal osteoporotic women had a lower serum level of Mg than the healthy controls (standardized mean difference [SMD]?=??0.55, 95 % confidence interval [CI]?=??0.83 to ?0.26). Further subgroup analysis found a similar pattern in Turkey (SMD?=??0.66, 95 % CI?=??0.99 to ?0.32) and Belgium (SMD?=??0.98, 95 % CI?=??1.91 to ?0.05), but not in China (SMD?=?0.02, 95 % CI?=??0.21 to 0.26). And the difference of serum level of Mg between postmenopausal osteoporotic women and healthy controls below the age of 60 years (SMD?=??0.61, 95 % CI?=??1.09 to ?0.13) was similar to that among the population over 60 years (SMD?=??0.49, 95 % CI?=??0.80 to ?0.18).In conclusion, this meta-analysis suggests that the low serum level of Mg seems to be a risk factor for OP among the postmenopausal women. However, the subgroup analysis found that there was contradiction regarding races and geography, like China and Turkey. Thus, this finding needs further confirmation by trans-regional multicenter study to obtain better understanding of causal relationships between serum Mg and postmenopausal OP.     

Serum and Hair Zinc Levels in Patients with Endemic Osteochondropathy in China: A Meta-analysis

A large number of studies have shown growing interest in the zinc (Zn) levels of serum and hair samples collected from patients with Kashin-Beck disease (KBD), an endemic chronic osteochondral disease. However, inconsistent conclusions regarding the serum and hair Zn levels have been made. The aim of this study is to assess and to explore the change in serum and hair Zn levels among KBD patients. Multiple databases, including PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and Technology of Chongqing (VIP), were carefully searched for available studies up to January 13, 2017 in this integrated analysis. Standard mean difference (SMD) with a 95% confidence interval (95% CI) was calculated using STATA 11.0. A total of 18 studies, involving 978 KBD cases and 1116 healthy controls, were collected in this analysis. Pooled analysis found the KBD patients had a higher hair Zn level and a lower serum Zn level than the healthy controls (hair Zn (μg/g), SMD = 0.030, 95% CI = ?0.315, 0.376; serum Zn (mg/L), SMD = ?0.069, 95%CI = ?0.924, 0.785). Meta-regression method and sensitivity analysis were utilized to analyze the heterogeneity of data. Positive correlations were separately identified between hair Zn level in KBD patients (r = 0.4639, P = 0.032) and controls (r = 0.4743, P = 0.012) and the survey year. No evidence of publication bias was observed. The available results suggest that increased hair Zn level and decreased serum Zn level are commonly found in KBD patients; however, the role of Zn in the etiology and pathogenesis of KBD could not yet be confirmed.     

Serum Selenium Levels and Cervical Cancer: Systematic Review and Meta-Analysis

Several studies have investigated the relationship between serum Se concentration and cervical cancer, but the results were inconsistent. Thus, we conducted a systematic review and meta-analysis to evaluate the association between serum selenium levels and cervical cancer. Twelve studies investigating the association by univariate analysis and five studies by multivariate analysis were identified after a systematic search of PubMed, Wanfang, CNKI, and SinoMed databases. Standard mean differences (SMD) or odds ratios (OR) with the corresponding 95% confidence intervals (CI) were pooled to compare the selenium levels between different groups. In univariate analysis, serum selenium levels in cervical cancer cases were significantly lower than in controls (SMD = ?4.86, 95% CI ?6.03–3.69). Subgroup analysis showed consistent results. In multivariate analysis, serum selenium levels in cervical cancer cases were also significantly lower than in controls (OR = 0.55, 95% CI 0.42–0.73). After treatment, the serum selenium levels increased significantly (SMD = 2.59, 95% CI 0.50–4.69). In conclusion, high serum selenium levels were associated with cervical cancer, and selenium exposure might be a protective factor for cervical cancer.     

Association Between Serum Zinc Levels and the Risk of Parkinson’s Disease: a Meta-Analysis

Recent studies have found that the serum zinc levels were associated with the risk of Parkinson’s disease (PD), but the results were inconsistent. Thus, we conducted a meta-analysis to summarize the evidence from observational studies between them. Pertinent studies were identified by a search in PubMed, Embase, and Web of science up to July, 10, 2016. Standardized mean difference (SMD) and 95% confidence intervals (CI) with random-effect model was used to combine the results. Subgroup analysis and meta-regression were also conducted. Publication bias was estimated using Begg’s regression asymmetry test. A total of 11 articles involving 822 PD patients and 777 healthy controls were included in the meta-analysis. Our meta-analysis results revealed that the serum zinc levels in PD patients were significantly lower than those in health controls (SMD = ?0.779, 95%CI = [?1.323, ?0.234], P < 0.001). The association was also significant oriental studies (SMD = ?1.601, 95%CI = [?2.398, ?0.805], P < 0.001). No publication bias was found. The current study indicated that serum zinc levels in PD patients were significantly lower than those in healthy controls.     

Fine mapping the KLK3 locus on chromosome 19q13.33 associated with prostate cancer susceptibility and PSA levels

Measurements of serum prostate-specific antigen (PSA) protein levels form the basis for a widely used test to screen men for prostate cancer. Germline variants in the gene that encodes the PSA protein (KLK3) have been shown to be associated with both serum PSA levels and prostate cancer. Based on a resequencing analysis of a 56?kb region on chromosome 19q13.33, centered on the KLK3 gene, we fine mapped this locus by genotyping tag SNPs in 3,522 prostate cancer cases and 3,338 controls from five case?Ccontrol studies. We did not observe a strong association with the KLK3 variant, reported in previous studies to confer risk for prostate cancer (rs2735839; P?=?0.20) but did observe three highly correlated SNPs (rs17632542, rs62113212 and rs62113214) associated with prostate cancer [P?=?3.41?×?10^?4, per-allele trend odds ratio (OR)?=?0.77, 95% CI?=?0.67?C0.89]. The signal was apparent only for nonaggressive prostate cancer cases with Gleason score <7 and disease stage <III (P?=?4.72?×?10^?5, per-allele trend OR?=?0.68, 95% CI?=?0.57?C0.82) and not for advanced cases with Gleason score >8 or stage ??III (P?=?0.31, per-allele trend OR?=?1.12, 95% CI?=?0.90?C1.40). One of the three highly correlated SNPs, rs17632542, introduces a non-synonymous amino acid change in the KLK3 protein with a predicted benign or neutral functional impact. Baseline PSA levels were 43.7% higher in control subjects with no minor alleles (1.61?ng/ml, 95% CI?=?1.49?C1.72) than in those with one or more minor alleles at any one of the three SNPs (1.12?ng/ml, 95% CI?=?0.96?C1.28) (P?=?9.70?×?10^?5). Together our results suggest that germline KLK3 variants could influence the diagnosis of nonaggressive prostate cancer by influencing the likelihood of biopsy.     

MTHFR polymorphisms and ovarian cancer risk: a meta-analysis

The C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been reported to alter the risk of ovarian cancer. However, the results are still inconclusive. For better understanding of the effect of these two polymorphisms on ovarian cancer risk, a meta-analysis was performed. An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and ovarian cancer risk was assessed by odds ratio (OR) with the corresponding 95?% confidence interval (95?% CI). 3,496 cases and 3,631 controls for C677T polymorphism and 3,280 cases and 3,346 controls for A1298C polymorphism were included in this meta-analysis. The results suggested that there were no significant associations between C677T and A1298C polymorphisms and ovarian cancer risk in overall comparisons in all genetic models (For C677T: TT vs. CC: OR?=?0.94, 95?% CI?=?0.71–1.24, P?=?0.65; CT vs. CC: OR?=?1.03, 95?% CI?=?0.93–1.14, P?=?0.57; TT/CT vs. CC: OR?=?1.01, 95?% CI?=?0.88–1.16, P?=?0.87; TT vs. CC/CT: OR?=?0.93, 95?% CI?=?0.72–1.20, P?=?0.58. For A1298C: CC vs. AA: OR?=?1.05, 95?% CI?=?0.88–1.25, P?=?0.65; CA vs. AA: OR?=?0.98, 95?% CI?=?0.88–1.08, P?=?0.66; CC/CA vs. AA: OR?=?0.99, 95?% CI?=?0.90–1.09, P?=?0.85; CC vs. AA/CA: OR?=?1.06, 95?% CI?=?0.90–1.26, P?=?0.46). Subgroup analysis based on ethnicities and influence analysis did not perturb the results. In conclusion, the results of this meta-analysis indicate that the MTHFR C677T and A1298C polymorphisms are not associated with ovarian cancer risk, especially in Caucasians.     

Quantitative assessment of the association between TP53 Arg72Pro polymorphism and bladder cancer risk

Previous studies investigating the association between TP53 Arg72Pro polymorphism and bladder cancer risk reported controversial results. To quantify the strength of association between TP53 Arg72Pro polymorphism and bladder cancer risk, we performed this meta-analysis. We searched PubMed, Embase and Wangfang databases for studies relating the association between TP53 Arg72Pro polymorphism and bladder cancer risk. We used the pooled odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) to assess the association. Finally, data were available from a total of 16 case–control studies including a total of 5, 545 subjects (2,345 cases and 3,200 controls). Meta-analysis of all 16 studies showed TP53 Arg72Pro polymorphism was not associated with bladder cancer risk (All P values were more than 0.10). Subgroup analyses by ethnicity showed that TP53 Arg72Pro polymorphism contributed to bladder cancer risk in East Asians in three genetic models (For Pro vs. Arg, Fixed-effects OR 1.18, 95 % CI 1.05–1.32; For ProPro vs. ArgArg, Fixed-effects OR 1.40, 95 % CI 1.11–1.77; For ProPro vs. ArgPro/ArgArg, Fixed-effects OR 1.32, 95 % CI 1.07–1.62). However, there was no significant association in Caucasians and the others (All P values were more than 0.05). Heterogeneity analyses suggested ethnicity was the major sources of heterogeneity. Thus, meta-analyses of available data suggest the Pro variant of TP53 Arg72Pro contributes to bladder cancer risk in East Asians. Besides, TP53 Arg72Pro polymorphism may have race-specific effects on bladder cancer risk and further studies are needed to elucidate this possible effect.     

Serum and Hair Nickel Levels and Breast Cancer: Systematic Review and Meta-Analysis

Several studies have investigated the relationship between serum and hair nickel (Ni) concentration and breast cancer, but the results were inconsistent. Thus, we conducted a systematic review and meta-analysis to evaluate the association between serum and hair nickel levels and breast cancer. Nine studies determining the serum nickel levels and six studies evaluating the hair nickel levels were identified in a systematic search of PubMed, China Knowledge Resource Integrated Database, Wanfang, and China Biomedical Literature Service System databases. Based on a random-effects model, standard mean differences (SMD) and the corresponding 95% confidence intervals (CI) were pooled to compare the nickel levels between different groups. Compared with healthy controls, the serum nickel levels in breast cancer were significantly higher (SMD (95% CI) 1.76 (0.82, 2.70)), as well as in those post-treated cases (SMD (95% CI) 2.56 (1.18, 3.94)). For breast cancer cases, the treatment made no significant decrease in serum nickel levels (SMD (95% CI) ?0.29 (?1.17, 0.59)). In hair, the nickel levels in breast cancer were slightly higher than in controls, but not significant (SMD (95% CI) 0.16 (?1.08, 1.40)). In conclusion, high serum nickel levels were associated with breast cancer, and nickel exposure might be a risk factor for breast cancer.     

Genetic polymorphisms in the CYP1A1 and CYP1B1 genes and susceptibility to bladder cancer: a meta-analysis

The current meta-analysis of case–control studies was conducted to evaluated the relationships of genetic polymorphisms in the CYP1A1 and CYP1B1 genes with the susceptibility to bladder cancer, aiming at determine whether these polymorphisms may contribute to the pathogenesis of bladder cancer. Related articles were determined via searching the following electronic databases without any language restrictions: PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases for relevant articles published before November 1st, 2013. STATA 12.0 software was also selected to deal with statistical data. The relationships were evaluated using the pooled odds ratios (ORs) and their 95 % confidence intervals (CI). Eleven case–control studies with a total of 2,609 bladder cancer patients and 2,634 healthy subjects met the inclusion criteria. The results of our meta-analysis demonstrated that CYP1A1 genetic polymorphisms were associated with increased risks of bladder cancer (allele model: RR = 1.18, 95 % CI 1.07–1.30, P = 0.001; dominant model: RR = 1.15, 95 % CI 1.05–1.27, P = 0.003; respectively), especially among 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms. A subgroup analysis by ethnicity was conducted to investigate its effect on susceptibility to bladder cancer. The subgroup analysis results revealed positive significant correlations between CYP1A1 genetic polymorphisms and bladder cancer risk among Asians (allele model: RR = 1.26, 95 % CI 1.10–1.44, P = 0.001; dominant model: RR = 1.22, 95 % CI 1.08–1.38, P = 0.001), but not among Caucasians (all P < 0.05). Nevertheless, we observed no significant correlations between CYP1B1 genetic polymorphisms and bladder cancer risk (all P > 0.05). Our meta-analysis indicates that CYP1A1 genetic polymorphisms may be involved in the pathogenesis of bladder cancer, especially among 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms. However, CYP1B1 genetic polymorphisms may not be important determinants of bladder cancer susceptibility.     

Effects of Pharmacological Concentrations of Dietary Zinc Oxide on Growth of Post-weaning Pigs: A Meta-analysis

Pharmacological dietary zinc (Zn) concentrations of 1,000 to 3,000 mg/kg diet from Zn oxide have been found to increase growth in post-weaning pigs. However, results were inconsistent among studies. A frequentist meta-analysis, in which effects were numerically described with standardized effect sizes (Hedges's g), was conducted in order to identify and quantify the responses in average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G/F) in post-weaning pigs upon dietary Zn supplementation from Zn oxide. The inability of independent continuous variables to explain significant heterogeneity obtained with fixed effect models necessitated the use of random effects models to calculate summary statistics. Dietary Zn supplementation increased (P?<?0.05) ADG (mean effect size?=?1.086, 95 % confidence intervals?=?0.905–1.266, 26 studies, 72 comparisons), ADFI (mean effect size?=?0.794, 95 % confidence intervals?=?0.616–0.971, 25 studies, 71 comparisons), and G/F (mean effect size?=?0.566, 95 % confidence intervals?=?0.422–0.710, 24 studies, 70 comparisons). Zinc oxide provided a feasible alternative to in-feed antibiotics to improve growth in post-weaning pigs, and its reduction in diets due to potential environmental pollution will have to be negated by alternative feed additives and management strategies in order to prevent economic losses.     

Cytochrome P450 1A1 (CYP1A1) gene polymorphisms and ovarian cancer risk: a meta-analysis

This meta-analysis aims to examine whether the genotype status of MspI, Ile462Val, and Thr461Asn polymorphisms in Cytochrome P450 1A1 (CYP1A1) is associated with ovarian cancer risk. Eligible case-control studies were identified through search in MEDLINE (end of search: October 2010). Pooled odds ratios (ORs) were appropriately derived from fixed effects or random effects models. Concerning MspI polymorphism, seven studies were eligible (1,051 cases and 1,613 controls); 11 studies were eligible (1,680 cases and 3,345 controls) for Ile462Val and three studies were eligible (349 cases and 785 controls) for Thr461Asn. Ile462Val polymorphism seemed to confer elevated ovarian cancer risk concerning homozygous carriers (pooled OR?=?2.65, 95?% CI: 1.40-5.03, p?=?0.003, fixed effects), as well as at the recessive model (pooled OR?=?2.10, 95?% CI: 1.13-3.92, p?=?0.020, fixed effects); these findings were replicated upon Caucasian subjects. MspI polymorphism was not associated with ovarian cancer risk (for heterozygous TC vs TT carriers pooled OR?=?1.10, 95?% CI: 0.91-1.34, p?=?0.329, fixed effects; for homozygous CC vs. TT carriers pooled OR?=?1.11, 95?% CI: 0.65-1.90, p?=?0.693, fixed effects). With respect to Thr461Asn polymorphism a finding of borderline statistical significance emerged, pointing to marginally elevated ovarian cancer risk in heterozygous Thr/Asn carriers (pooled OR?=?1.62, 95?% CI: 0.97-2.70, p?=?0.066, fixed effects), but not in homozygous Asn/Asn carriers (pooled OR?=?1.40, 95?% CI: 0.18-10.89, p?=?0.749, fixed effects). Ile462Val status seems to represent a meaningful risk factor for ovarian cancer in Caucasians. Additional case-control studies of high methodological quality are needed in order to further substantiate and enrich the present findings. Special attention should be paid upon the design of future studies; Asian and African populations should represent points of focus.     

Fluoride Alters Serum Elemental (Calcium,Magnesium, Copper,and Zinc) Homeostasis Along with Erythrocyte Carbonic Anhydrase Activity in Fluorosis Endemic Villages and Restores on Supply of Safe Drinking Water in School-Going Children of Nalgonda District,India

The present study aimed to determine the serum trace elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg)) along with erythrocyte carbonic anhydrase (CA) activity and effect of intervention with safe drinking water for 5 years in the school children of fluorosis endemic area. For this purpose, three categories of villages were selected based on drinking water fluoride (F): Category I (control, F?=?1.68 mg/L), category II (affected F?=?3.77 mg/L), and category III (intervention village) where initial drinking water F was 4.51 mg/L, and since the last 5 years, they were drinking water containing <?1.0 mg/L F. The results revealed that urinary F was significantly (P?<?0.05) higher in category II compared to categories I and III. A significant (P?<?0.05) increase in serum Cu and Mg was observed in category II compared to category I. Serum Zn and Ca was significantly (P?<?0.05) decreased in categories II and III compared to category I. The erythrocyte CA activity was decreased in the category II compared to category I. However, in the category III, erythrocyte CA activity was comparable to the control group. In conclusion, F exposure altered elemental homeostasis which has restored to some extent on intervention by safe drinking water for 5 years in school-going children.     

miR-499 rs3746444 polymorphism is associated with cancer development among Asians and related to breast cancer susceptibility

To derive a more precise estimation of the relationship between miR-499 rs3746444 polymorphism (A>G) and cancer risk, a meta-analysis was performed. A total of 9 studies including 6,077 cases and 7,199 controls were involved in this meta-analysis. Overall, no significantly elevated cancer risk was associated with miR-499 G allele when all studies were pooled into the meta-analysis (AG vs. AA: OR?=?1.14, 95?% CI?=?0.98–1.32; GG vs. AA: OR?=?1.12, 95?% CI?=?0.95–1.33; dominant model: OR?=?1.13, 95?% CI?=?0.99–1.29; recessive model: OR?=?1.05, 95?% CI?=?0.83–1.33). In the subgroup analysis by ethnicity, significantly increased risk was only found for Asians (dominant model: OR?=?1.22, 95?% CI?=?1.02–1.46). When stratified by study design, no statistically significantly elevated risks were found in hospital-based studies or population-based studies. In the subgroup analysis by cancer type, significant cancer risk change was only found for breast cancer when miR-499 G allele was included (dominant model: OR?=?1.13, 95?% CI?=?1.01–1.26). In conclusion, this meta-analysis suggests that the miR-499 rs3746444 polymorphism (A>G) is a low-penetrant risk factor for cancer development among Asians and may contribute to breast cancer susceptibility.     

Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis

The previous published data on the association between the 8-oxo-guanine glycosylase-1 (OGG1) and apurinic/apyrimidinic-endonuclease-1 (APEX1/APE1) polymorphisms and lung cancer risk remained controversial. Several polymorphisms in the OGG1 and APEX1 gene have been described, including the commonly occurring Ser326Cys in OGG1 and Asp148Glu in APEX1. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 37 studies were identified to the meta-analysis, including 9,203 cases and 10,994 controls for OGG1 Ser326Cys (from 25 studies) and 3,491 cases and 4,708 controls for APEX1 Asp148Glu (from 12 studies). When all the eligible studies were pooled into the meta-analysis of OGG1 Ser326Cys polymorphism, significantly increased lung cancer risk was observed in recessive model (OR?=?1.17, 95?% CI?=?1.03–1.33) and in additive model (OR?=?1.21, 95?% CI?=?1.03–1.42). In the stratified analysis, significantly increased risk of lung cancer was also observed on the population-based studies (recessive model: OR?=?1.26, 95?% CI?=?1.08–1.46, additive model: OR?=?1.42, 95?% CI?=?1.06–1.73) and non-smokers (dominant model: OR?=?1.20, 95?% CI?=?1.02–1.42, recessive model: OR?=?1.20, 95?% CI?=?1.02–1.40, additive model: OR?=?1.35, 95?% CI?=?1.08–1.68). Additionally, when one study was deleted in the sensitive analysis, the results of OGG1 Ser326Cys were changed in Asians (recessive model: OR?=?1.16, 95?% CI?=?1.06–1.27, additive model: OR?=?1.23, 95?% CI?=?1.09–1.38). When all the eligible studies were pooled into the meta-analysis of APEX1 Asp148Glu polymorphism, there was no evidence of significant association between lung cancer risk and APEX1 Asp148Glu polymorphism in any genetic model. In the stratified analysis, significantly decreased lung adenocarcinoma risk was observed in recessive model (OR?=?0.68, 95?% CI?=?0.48–0.97, P _h?=?0.475, I²?=?0.0?%). Additionally, when one study was deleted in the sensitive analysis, the results of APEX1 Asp148Glu were changed in Asians (recessive model: OR?=?1.21, 95?% CI?=?1.03–1.43) and smokers (dominant model: OR?=?1.62, 95?% CI?=?1.08–2.44, additive model: OR?=?1.37, 95?% CI?=?1.02–1.84). In summary, this meta-analysis indicates that OGG1 Ser326Cys show an increased lung cancer risk in Asians and non-smokers, APEX1 Asp148Glu polymorphism may be associated with decreased lung adenocarcinoma risk, and APEX1 Asp148Glu polymorphism show an increased lung cancer risk in Asians and smokers. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk.     

Association between p53 codon 72 genetic polymorphisms and tobacco use and lung cancer risk in a Chinese population

Genetic polymorphisms of p53 codon 72 are thought to have significant effects on the metabolism of environmental carcinogens and thus on lung cancer risk, but the reported results are not always consistent. The aim of this study is to investigate the relationship between p53 codon 72 genetic polymorphisms and tobacco use and lung cancer risk in a Chinese population. A population-based control study was conducted in 360 lung cancer patients and 360 cancer-free controls. The genotype of the p53 codon 72 was determined by using a polymerase chain reaction?Crestriction fragment length polymorphism assay. Patients with lung cancer had a significantly lower frequency of Pro/Pro genotype [odds ratio (OR)?=?0.58, 95?% confidence interval (CI)?=?0.40, 0.84; P?=?0.004] and Pro allele (OR?=?0.72, 95?% CI?=?0.59, 0.89; P?=?0.002) than controls. Patients with squamous cell carcinoma had also a significantly lower frequency of Pro/Pro genotype (OR?=?0.45, 95?% CI?=?0.25, 0.82; P?=?0.009). In the analysis combining p53 codon 72 polymorphisms and smoking, smokers who had smoked for more than 30 pack-years had a significantly lower frequency of Pro/Pro genotype (OR?=?0.52, 95?% CI?=?0.30, 0.92; P?=?0.03) compared with non-smokers. This study suggests that p53 codon 72 polymorphisms play a role in the development of lung cancer and modifies the risk for smoking-related lung cancer in a Chinese population.     

Association Between Circulating Copeptin Level and Mortality Risk in Patients with Intracerebral Hemorrhage: a Systemic Review and Meta-Analysis

Copeptin has been identified as a biomarker of disease severity and is associated with mortality risk in several common diseases. This study sought to determine the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. PubMed, Web of Science, and Wanfang Medicine Database were searched for studies assessing the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. The pooled hazard ratio (HR) of mortality was calculated and presented with 95 % confidence interval (95 % CI). Data from 1332 intracerebral hemorrhage patients were derived from 9 studies. Meta-analysis showed that intracerebral hemorrhage patients with poor prognosis had much higher copeptin levels than those survivors (standardized mean difference?=?1.68, 95 % CI 1.26–2.11, P?<?0.00001). Meta-analysis of 8 studies with HRs showed that high circulating copeptin level was associated with higher risk of mortality in patients with intracerebral hemorrhage (HR?=?2.42, 95 % CI 1.60–3.65, P?<?0.0001). Meta-analysis of 6 studies with adjusted HRs showed that high circulating copeptin level was independently associated with higher risk of mortality in patients with intracerebral hemorrhage (HR?=?1.67, 95 % CI 1.26–2.22, P?=?0.0003). Our study suggests that there is an obvious association between circulating copeptin level and mortality in patients with intracerebral hemorrhage. High circulating copeptin level is independently associated with higher risk of mortality in patients with intracerebral hemorrhage.     

The Relationship Between Selenium Levels and Breast Cancer: A Systematic Review and Meta-Analysis

Breast cancer is the most common cancer type. In several studies, hints have been provided that there is a correlation between selenium deficiency and the incidence of breast cancer. Findings of these published reports are, however, inconsistent. This study serves as a pioneering study aiming at combining the results of studies using a meta-analytic method. A total of 16 articles published between 1980 and 2012 worldwide were selected through searching PubMed, Scopus, and Google scholar databases, and the information were analyzed using a meta-analytic method [random effects model]. I ² statistics were used to examine heterogeneity. The information was then analyzed by STATA version 12. In this study, due to the non-uniform methods used to measure selenium concentrations, selenium levels were measured in the various subgroups in both case and control groups. There were significant correlations between selenium concentration and breast cancer [P?<?0.05]. Hence, the mean risk differentiating criteria were estimated to be 0.63 [95 % confidence interval [95% CI] 0.93 to 0.32] in serum and toenails. Subgroup analysis showed that the value in toenails was ?0.07 [95% CI ?0.16 to 0.03] and in serum ?1.04 [95% CI 1.71 to ?0.38]. In studies in which selenium concentrations were measured in serum, a significant correlation was observed between selenium concentration and breast cancer. In contrast, in studies in which selenium concentration was measured in toenails, the correlation was not significant. Therefore, the selenium concentration can be used as one predictor for breast cancer.