-
1.
Ovarian cancer risk according to circulating zinc and copper concentrations: A meta-analysis and Mendelian randomization study.
Lin, S, Yang, H
Clinical nutrition (Edinburgh, Scotland). 2021;(4):2464-2468
Abstract
BACKGROUND & AIMS Ovarian cancer is a lethal disease with few modifiable risk factors. Circulating zinc and copper are potential biomarkers for ovarian cancer; however, evidence of their causal effects are scarce. This study aimed to examine the impact of circulating zinc and copper concentrations on ovarian cancer risk, using meta-analysis and Mendelian randomization (MR) approaches. METHODS Twenty case-control studies, including 699 patients with ovarian cancer, 567 patients with benign ovarian lesions, and 1194 healthy controls, were selected for meta-analysis. With a Two-sample MR approach, genetic instruments of 21 single nucleotide polymorphisms (SNPs) associated with circulating zinc and 25 SNPs associated with circulating copper were created. Their genetic associations with ovarian cancer were extracted from a genome-wide association study of 25,509 ovarian cancer cases and 40,941 controls. RESULTS Ovarian cancer patients had significantly lower concentrations of circulating zinc than healthy controls (Standardized mean differences [SMD] = -1.01, 95% CI: -1.38 to -0.64). In contrast, circulating copper concentrations were significantly higher in ovarian cancer patients (SMD = 1.46, 95% CI: 0.82 to 2.09). In MR analysis, we only found increased circulating zinc concentration causally associated with a lower risk of ovarian cancer (odds ratio = 0.968, 95% CI: 0.941 to 0.995, per SD of ranked-inverse normalized concentration), especially in the high-grade serous subtype. CONCLUSIONS Although increased circulating copper and decreased zinc concentrations were found in ovarian cancer patients, a suggestive causal association was only detected with zinc concentration, suggesting further studies on zinc interventions for ovarian cancer might have clinical impact.
-
2.
Association Between the Change of Serum Copper and Ischemic Stroke: a Systematic Review and Meta-Analysis.
Zhang, M, Li, W, Wang, Y, Wang, T, Ma, M, Tian, C
Journal of molecular neuroscience : MN. 2020;(3):475-480
Abstract
Ischemic stroke is the most common stroke subtypes with all strokes. More and more studies found that serum copper was related to the ischemic stroke. However, the correlation between serum copper and ischemic stroke was inconsistent. We performed the meta-analysis to assess the association between the change of serum copper and ischemic stroke. Electronic databases were identified to search for relevant studies about serum copper and ischemic stroke from inception to February 28, 2019. Eight studies with a total of 777 participants were included into this meta-analysis. Because of high heterogeneity (I2 = 71%), we chose a random effect model. Our results showed the serum copper levels were significantly higher in ischemic stroke group compared with controls group (pooled mean difference, 1.25; 95% confidence intervals (CIs), 0.07-2.43; P = 0.04), in particular studies after the year of 2009 (I2 = 0%; pooled mean difference, 2.16; 95% CI, 1.37-2.95; P < 0.00001). Serum copper was associated with ischemic stroke, and it may be one of the risk factors of ischemic stroke.
-
3.
Serum copper and zinc levels in breast cancer: A meta-analysis.
Feng, Y, Zeng, JW, Ma, Q, Zhang, S, Tang, J, Feng, JF
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2020;:126629
Abstract
BACKGROUND More 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 METHODS Studies 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. RESULTS Thirty-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. CONCLUSION The 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.
-
4.
Biomarkers for diagnosis of Wilson's disease.
Ryan, A, Nevitt, SJ, Tuohy, O, Cook, P
The Cochrane database of systematic reviews. 2019;(11)
-
-
Free full text
-
Abstract
BACKGROUND Wilson's disease, first described by Samuel Wilson in 1912, is an autosomal recessive metabolic disorder resulting from mutations in the ATP7B gene. The disease develops as a consequence of copper accumulating in affected tissues. There is no gold standard for the diagnosis of Wilson's disease, which is often delayed due to the non-specific clinical features and the need for a combination of clinical and laboratory tests for diagnosis. This delay may in turn affect clinical outcome and has implications for other family members in terms of diagnosis. The Leipzig criteria were established to help standardise diagnosis and management. However, it should be emphasised that these criteria date from 2003, and many of these have not been formally evaluated; this review examines the evidence behind biochemical testing for Wilson's disease. OBJECTIVES To determine the diagnostic accuracy of three biochemical tests at specified cut-off levels for Wilson's disease. The index tests covered by this Cochrane Review are caeruloplasmin, 24-hour urinary copper and hepatic copper content. These tests were evaluated in those with suspected Wilson's disease and appropriate controls (either healthy or those with chronic liver disease other than Wilson's). In the absence of a gold standard for diagnosing Wilson's disease, we have used the Leipzig criteria as a clinical reference standard. To investigate whether index tests should be performed in all individuals who have been recommended for testing for Wilson's disease, or whether these tests should be limited to subgroups of individuals. SEARCH METHODS We identified studies by extensive searching of, e.g. the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, the Web of Science and clinical trial registries (29 May 2019). Date of the most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Inborn Errors of Metabolism Register: 29 May 2019. SELECTION CRITERIA We included prospective and retrospective cohort studies that assessed the diagnostic accuracy of an index test using the Leipzig criteria as a clinical reference standard for the diagnosis of Wilson's disease. DATA COLLECTION AND ANALYSIS Two review authors independently reviewed and extracted data and assessed the methodological quality of each included study using the QUADAS-2 tool. We had planned to undertake meta-analyses of the sensitivity, specificity at relevant cut-offs for each of the biochemical tests for Wilson's, however, due to differences in the methods used for each biochemical index test, it was not possible to combine the results in meta-analyses and hence these are described narratively. MAIN RESULTS Eight studies, involving 5699 participants (which included 1009 diagnosed with Wilson's disease) were eligible for inclusion in the review. Three studies involved children only, one adults only and the four remaining studies involved both children and adults. Two evaluated participants with hepatic signs and six with a combination of hepatic and neurological signs and symptoms of Wilson's disease, as well as pre-symptomatic individuals. The studies were of variable methodological quality; with high risk if bias for participant selection and the reference standard used being of greatest methodological concern. Key differences between studies include differences in assay methodology, different cut-off values for diagnostic thresholds, different age and ethnicity groups. Concerns around study design imply that diagnostic accuracy figures may not transfer to populations outside of the relevant study. INDEX TEST caeruloplasmin Five studies evaluated various thresholds of caeruloplasmin (4281 participants, of which 541 had WD). For caeruloplasmin a cut-off of 0.2 g/L as in the Leipzig criteria achieved a sensitivity of 77.1% to 99%, with variable specificity of 55.9% to 82.8%. Using the cut-off of 0.1 g/L of the Leipzig criteria seemed to lower the sensitivity overall, 65% to 78.9%, while increasing the specificity to 96.6% to 100%. INDEX TEST hepatic copper Four studies evaluated various thresholds of hepatic copper (1150 participants, of which 367 had WD). The hepatic copper cut-off of 4 μmol/g used in the Leipzig criteria achieved a sensitivity of 65.7% to 94.4%, with a variable specificity of 52.2% to 98.6%. INDEX TEST 24-hour urinary copper Three studies evaluated various thresholds of 24-hour urinary copper (268 participants, of which 101 had WD). For 24-hour urinary copper, a cut-off of 0.64 to 1.6 μmol/24 hours used in the Leipzig criteria achieved a variable sensitivity of 50.0% to 80.0%, with a specificity of 75.6% to 98.3%. AUTHORS' CONCLUSIONS The cut-offs used for caeruloplasmin, 24-hour urinary copper and hepatic copper for diagnosing Wilson's disease are method-dependent and require validation in the population in which such index tests are going to be used. Binary cut-offs and use of single-test strategies to rule Wilson's disease in or out is not supported by the evidence in this review. There is insufficient evidence to inform testing in specific subgroups, defined by age, ethnicity or clinical subgroups.
-
5.
The association of serum zinc and copper with hypertension: A meta-analysis.
Li, Z, Wang, W, Liu, H, Li, S, Zhang, D
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2019;:41-48
Abstract
OBJECTIVE The association of serum zinc (Zn), copper (Cu) with the risk of hypertension (HT) remains controversial. Therefore, we conducted a meta-analysis to explore the relationships. METHODS We searched relevant literatures on PubMed and Web of Science up to September 2018. Pooled standard mean difference (SMD) with corresponding 95% confidence interval (CI) was calculated by random effects model.I2 was used to evaluate heterogeneity among studies. RESULTS 25 articles of serum Zn and 22 articles of serum Cu were included in meta-analysis. HT patients had lower serum Zn [SMD (95%CI): -0.612(-0.951, -0.274), z = 3.54, Pfor z <0.001; I2 = 97.0%, PforI2 <0.001], whereas no significant difference of serum Cu was shown between HT patients and controls [SMD (95%CI): 0.153(-0.101, 0.407)]. Also, male HT patients had lower serum Zn [SMD (95%CI): -1.443(-2.868, -0.017), z = 1.98, Pfor z = 0.047; I2 = 98.8%, PforI2 <0.001]. In subgroup analysis, a lower serum Zn was observed in HT patients in studies conducted in Europe [-1.066(-1.759, -0.374)], in case-control studies [-0.718(-1.294, -0.142)], in matched case-control studies [-0.939(-1.646, -0.233)] and studies involving treated patients [-1.416(-2.195, -0.638)]. Meanwhile, a higher serum Cu was found in HT patients in studies conducted in Africa [1.96(1.402, 2.518)], and in matched case-control studies [0.655(0.204, 1.107)]. CONCLUSION The present meta-analysis indicates that serum Zn level in HT patients was significantly lower than that in controls, while no significantly different serum Cu level was found between HT patients and controls. Future studies are needed to confirm these results in future research.
-
6.
Association between serum copper and heart failure: a meta-analysis.
Huang, L, Shen, R, Huang, L, Yu, J, Rong, H
Asia Pacific journal of clinical nutrition. 2019;(4):761-769
Abstract
BACKGROUND AND OBJECTIVES Copper dyshomeostasis can lead to many diseases, including cardiovascular disease. However, there are conflicting reports on the relationship between serum copper and heart failure (HF). To explore the relationship between serum copper levels and HF by performing a meta-analysis. METHODS AND STUDY DESIGN The PubMed and ScienceDirect databases until June 2019 were searched for reports on the association between serum copper levels and HF. RESULTS A total of thirteen studies including 1504 subjects were chosen for the meta-analysis. The pooled analysis indicated that patients with HF had higher serum copper than the control subjects [standardized mean difference (SMD), 0.982; 95% confidence interval (CI), (0.679, 1.285)]. Subgroup analysis stratified by different geographic locations found that HF patients had higher copper than the control subjects in Asia and Europe [Asia: SMD, 0.948 and 95% CI, (0.569, 1.327); Europe: SMD, 1.275 and 95% CI, (0.633, 1.917)], but not in America [America: SMD, 0.637 and 95% CI, (-0.109, 1.383)]. Additionally, subgroup analysis revealed that patients with ischemic cardiomyopathy (ICM) [SMD, 1.171; 95% CI, (0.717, 1.624)], idiopathic dilated cardiomyopathy (IDCM) [SMD, 0.569; 95% CI, (0.097, 1.042)] and other types of HF [SMD, 1.152; 95% CI, (0.594, 1.710)] all had higher copper levels than controls. Further subgroup analysis stratified by Newcastle-Ottawa Scale (NOS) scores also found higher serum copper in patients with HF than controls within each subgroup. CONCLUSIONS Our meta-analysis identified a significant association between high serum copper and HF.
-
7.
Association between serum copper levels and cervical cancer risk: a meta-analysis.
Zhang, M, Shi, M, Zhao, Y
Bioscience reports. 2018;(4)
Abstract
Whether serum copper levels were higher in patients with cervical cancer than that in controls was controversial. Hence, we conducted the present study to explore the relationship between serum copper levels and cervical cancer. We searched PubMed, WanFang, and China National Knowledge Internet (CNKI) for relevant studies before November 30, 2017. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to combine results across studies using the random-effect model. A total of 14 publications involving 747 patients with cervical cancer and 1014 controls were eligible through inclusion criteria. In comparison with controls, serum copper levels were significantly higher in patients with cervical cancer [summary SMD = 1.35; 95%CI: 0.10-2.59], with significant heterogeneity (I2 = 98.8%; P<0.001) was found. Significant association was also found among Asian populations [summary SMD = 1.39; 95%CI: 0.06-2.71]. The association was positive in subgroup analysis of population-based case-control studies (PBCC) [summary SMD = 1.64; 95%CI: 0.02-3.34], but not in hospital-based case-control studies (HBCC). Through a sensitivity analysis, we did not identify any single study to strongly influence the results of our serum copper levels and cervical cancer risk. No publication bias was found in our analysis. In conclusion, our study provided significant evidence of higher serum copper levels in patients with cervical cancer than in controls, suggesting that serum copper exposure was a risk factor on cervical cancer.
-
8.
Association between serum copper levels and lung cancer risk: A meta-analysis.
Zhang, X, Yang, Q
The Journal of international medical research. 2018;(12):4863-4873
Abstract
OBJECTIVE To evaluate the association between serum copper levels and lung cancer risk. METHODS We searched the electronic PubMed, WanFang, CNKI, and SinoMed databases to identify studies including information on serum copper levels and lung cancer. Standard mean differences and corresponding 95% confidence intervals were calculated using Stata 12.0 software. We performed a meta-analysis on the identified studies overall and according to geographic location. We also evaluated heterogeneity among the studies and the occurrence of publication bias. RESULTS Thirty-three articles including 3026 cases and 9439 controls were included in our study. The combined results showed that serum copper levels were higher in patients with lung cancer compared with controls without lung cancer, though the results showed high heterogeneity. In a subgroup analysis according to geographic location, significant associations between copper levels and lung cancer were found for both Asian and European populations. No publication bias was detected in this meta-analysis. CONCLUSIONS High serum copper levels could increase the risk of lung cancer, suggesting that environmental copper exposure may be a risk factor for the development of lung cancer.