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XPD Lys751Gln and Asp312Asn Polymorphisms and Susceptibility to Skin Cancer: A Meta-Analysis of 17 Case-control Studies

  • Zhu, Hai-Li;Bao, Ji-Ming;Lin, Pei-Xin;Li, Wen-Xia;Zou, Zhen-Ning;Huang, Ye-En;Chen, Qing;Shen, Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6619-6625
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    • 2014
  • Background: Numerous studies have explored the influence of XPD Lys751Gln and/or Asp312Asn polymorphisms on skin cancer susceptibility. However, the results remain inconclusive. To derive a more precise estimation, we conducted a comprehensive search to identify all available published studies and performed a meta-analysis. Materials and Methods: Electronic literature searches of the PubMed, CBM and CNKI databases were performed up to March 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of associations. Results: Seventeen case-control studies were included with a total sample size of 6, 113 cases and 11, 074 controls for the XPD Lys751Gln polymorphism, and 10 studies (3, 840cases and 7, 637 controls) for the XPD Asp312Asn polymorphism were pooled for analysis. Overall, no significant associations were found between the XPD Lys751Gln polymorphism and skin cancer risk in any genetic model. On stratified analysis by tumor type, XPD Lys751Gln polymorphism was not associated with increased risk of non-melanoma skin cancer, but was significantly related with increased risk of cutaneous melanoma (Gln/Gln vs Lys/Lys: OR=1.15, 95%CI=1.02-1.29, p=0.023; dominant model: OR=1.09, 95%CI=1.01-1.18, p=0.036). For the XPD Asp312Asn polymorphism, no significant association with skin cancer risk was observed in overall or subgroup analyses. Conclusions: The present meta-analysis suggests that the XPD Lys751Gln polymorphism may contribute to the risk of cutaneous melanoma from currently available evidence. Further investigations are needed to obtain more insight into possible roles of these two polymorphisms in skin carcinogenesis.

Role of P14 and MGMT Gene Methylation in Hepatocellular Carcinomas: a Meta-analysis

  • Li, Cheng-Cheng;Yu, Zhuang;Cui, Lian-Hua;Piao, Jin-Mei;Liu, Meng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6591-6596
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    • 2014
  • Background: This meta-analysis was performed to investigate the relationship between methylation of the P14 and O6-methylguanine-DNA methyltransferase (MGMT) genes and the risk of hepatocellular carcinoma (HCC). Materials and Methods: We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) databases to identify relevant studies that analysed HCC tissues for P14 and MGMT gene methylation status; we then performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to evaluate the association between gene methylation and the risk of HCC. Results: Ten studies that assessed P14 gene methylation in 630 HCC tumour tissues and nine studies analysing MGMT methylation in 497 HCC tumour tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P14 methylation was significantly higher in HCCs than in adjacent tissues (OR 3.69, 95%CI 1.63-8.35, p=0.002), but there was no significant difference in MGMT methylation between HCC and adjacent tissues (OR 1.76, 95%CI 0.55-5.64, p=0.34). A subgroup analysis according to ethnicity revealed that P14 methylation was closely related to the risk of HCC in Chinese and Western individuals (Chinese, OR 7.74, 95%CI 1.36-44.04, p=0.021; Western, OR 3.60, 95%CI 1.49-8.69, p=0.004). Furthermore, MGMT methylation was not correlated with the risk of HCC in Chinese individuals (OR 2.42, 95%CI 0.76-7.73, p=0.134). The combined rate of P14 methylation was 35% (95%CI 24-48%) in HCC tumour tissues and 11% (95%CI 4-27%) in adjacent tissues, whereas the combined rate of MGMT methylation was 15% (95%CI 6-32%) in HCC and 10% (95%CI 4-22%) in adjacent tissues. Conclusions: These results suggest that the risk of HCC is related to P14 methylation, but not MGMT methylation. Therefore, P14 gene methylation may be a potential biomarker for the diagnosis of HCC.

The 765G>C Polymorphism in the Cyclooxygenase-2 Gene and Gastric Cancer Risk: an Update by Meta-analysis

  • Zhao, Fen;Zhu, Hong;Huang, Min;Yi, Cheng;Huang, Ying
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2863-2868
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    • 2014
  • Background: The 765G>C polymorphism in cyclooxygenase-2 (COX-2) gene has been extensively investigated for association with gastric cancer (GC). However, the results of different studies have been inconsistent. The aim of this study is to comprehensively evaluate the genetic risk of -765G>C polymorphism in the COX-2 gene for GC. Materials and Methods: We searched Pubmed, Embase, Medline, CNKI database, Wanfang database, Weipu database, and Chinese Biomedical database, covering all publications (last search been performed on Jan 10, 2014). Statistical analyses were performed using Revman 5.2 and STATA 10.0 software. Results: A total of 1,874 cases and 3,005 controls in 10 case-control studies were included in this meta-analysis. The results indicated that the variant C allele carriers (GC+CC) had a 69% increased risk of GC when compared with the homozygote GG (odds ratio (OR)=1.69, 95% confidence interval (CI), 1.10-2.61 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers in Asians (OR=1.75, 95%CI=1.40-2.18, and p<0.00001) and in Indians (OR=8.38, 95%CI=4.34-16.16, and p<0.00001) but not in Caucasians (OR=1.07, 95%CI=0.81-1.42, and p=0.62) or in Dutch (OR=0.53, 95%CI= 0.33-0.87, and p= 0.01).In the subgroup analysis by Helicobacter pylori (H. pylori) status, a significantly increased risk was identified among H. pylori (+) (OR=3.58, 95%CI=2.33-3.50, and p<0.00001) and H. pylori (-) (OR=2.32, 95%CI=1.46-3.69, and p=0.0004). Conclusions: This meta-analysis suggested that the -765G>C polymorphism in the COX-2 gene could be a risk factor for GC in Asians and Indians.

Tumor Necrosis Factor-α Gene Polymorphisms and Risk of Oral Cancer: Evidence from a Meta-analysis

  • Chen, Fang-Chun;Zhang, Fan;Zhang, Zhi-Jiao;Meng, Si-Ying;Wang, Yang;Xiang, Xue-Rong;Wang, Chun;Tang, Yu-Ying
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7243-7249
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    • 2013
  • Numerous studies have been conducted regarding association between TNF-${\alpha}$ and oral cancer risk, but the results remain controversial. The present meta-analysis is performed to acquire a more precise estimation of relationships. Databases of Pubmed, the Cochrane library and the China National Knowledge Internet (CNKI) were retrieved until August 10, 2013. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated with fixed- or random-effect models. The heterogeneity assumption was assessed by I-squared test. Among the eight included case-control studies, all were focused on TNF-${\alpha}$-308G>A and four also concerned the TNF-${\alpha}$-238G>A polymorphism. It was found that oral cancer risk were significant decreased with the TNF-${\alpha}$-308G>A polymorphism in the additive genetic model (GG vs. AA, OR=0.19, 95% CI: [0.04, 1.00], P=0.05, I2=68.9%) and the dominant genetic model (GG+GA vs. AA, OR=0.22, 95% CI: [0.06, 0.82], P=0.03, I2=52.4%); however, no significant association was observed in allele contrast (G vs. A, OR=0.70, 95% CI: [0.23, 2.16], P=0.54, I2=95.9%) and recessive genetic models (GG vs. GA+AA, OR=0.72, 95% CI: [0.33, 1.57], P=0.41, I2=93.1%). For the TNF-${\alpha}$-238G>A polymorphism, significant associations with oral cancer risk were found in the allele contrast (G vs. A, OR=2.75, 95% CI: [1.25, 6.04], P=0.01, I2=0.0%) and recessive genetic models (GG vs. GA+AA, OR=2.23, 95%CI: [1.18, 4.23], P=0.01, I2=0.0%). Conclusively, this meta-analysis indicates that TNF-${\alpha}$ polymorphisms may contribute to the risk of oral cancer. Allele G and the GG+GA genotype of TNF-${\alpha}$-308G>A may decrease the risk of oral cancer, while allele G and the GG genotype of TNF-${\alpha}$-238G>A may cause an increase.

Intraperitoneal Perfusion Therapy of Endostar Combined with Platinum Chemotherapy for Malignant Serous Effusions: A Meta-analysis

  • Liang, Rong;Xie, Hai-Ying;Lin, Yan;Li, Qian;Yuan, Chun-Ling;Liu, Zhi-Hui;Li, Yong-Qiang
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8637-8644
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    • 2016
  • Background: Malignant serous effusions (MSE) are one complication in patients with advanced cancer. Endostar is a new anti-tumor drug targeting vessels which exerts potent inhibition of neovascularization. This study aimed to systematically evaluate the efficacy and safety of intraperitoneal perfusion therapy of Endostar combined with platinum chemotherapy for malignant serous effusions (MSE). Materials and Methods: Randomized controlled trials (RCTs) on intraperitoneal perfusion therapy of Endostar combined with platinum chemotherapy for malignant serous effusions were searched in the electronic data of PubMed, EMBASE, Web of Science, CNKI, VIP, CBM and WanFang. The quality of RCTs was evaluated by two independent researchers and a meta-analysis was performed using RevMan 5.3 software. Results: The total of 25 RCTs included in the meta-analysis covered 1,253 patients, and all literature quality was evaluated as "B" grade. The meta-analysis showed that Endostar combined with platinum had an advantage over platinum alone in terms of response rate of effusions (76% vs 48%, RR=1.63, 95%CI: 1.50-1.78, P<0.00001) and improvement rate in quality of life (69% vs 44%, RR=1.57, 95%CI: 1.42-1.74, P<0.00001). As for safety, there was no significant difference between the two groups in the incidences of nausea and vomiting (35% vs 34%, RR=1.01, 95%CI: 0.87-1.18, P=0.88), leucopenia (38% vs 38%, RR=1, 95%CI: 0.87-1.15, P=0.99), and renal impairment (18% vs 20%, RR=0.86, 95%CI: 0.43-1.74, P=0.68). Conclusions: Endostar combined with platinum by intraperitoneal perfusion is effective for malignant serous effusions, and patient quality of life is significantly improved without the incidence of adverse reactions being obviously increased.

Contribution of Macrophage Migration Inhibitory Factor -173G/C Gene Polymorphism to the Risk of Cancer in Chinese Population

  • Wang, Cheng-Di;Li, Tai-Ming;Ren, Zheng-Ju;Ji, Yu-Lin;Zhi, Liu-Shou
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4597-4601
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    • 2015
  • Background: Macrophage migration inhibitory factor (MIF) -173G/C (rs755622) gene polymorphism has been associated with cancer risk. Previous studies have revealed that MIF -173G/C gene polymorphism may increase cancer in the Chinese population, while results of individual published studies remain inconsistent and inconclusive.We performed this meta-analysis to derive a more precise estimation of the relationship. Materials and Methods: We conducted a search on PubMed, Embase, MEDLINE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang, Weipu on Dec 31, 2014.Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the association. A total of eight studies including 2,186 cases and 2,285 controls were involved in this meta-analysis. Results: The pooled results indicated the significant association between MIF -173G/C polymorphism and the risk of cancer for Chinese population (CC + CG vs GG: OR=1.14, 95%CI=1.02-127, pheterogeneity<0.01; P=0.023; CC vs CG+GG: OR=1.12, 95%CI=1.02-1.23, pheterogeneity<001; P=0.017;CC vs GG: OR=1.18, 95%CI=1.04-1.33, pheterogeneity<001; P=0.008; CG vs GG:OR=1.03, 95%CI=0.91-1.15, pheterogeneity<001; P=0.656; C vs G:OR=1.24, 95%CI=1.14-1.25, pheterogeneity<001; P<001). Subgroup analysis showed that in patients with "solid tumors", heterogeneity was very large (OR=0.94,95%CI=0.83-1.06,pheterogeneity=0.044; p=0.297). Within "non-solid tumors", the association became even stronger (OR=6.62, 95 % CI=4.32-10.14, pheterogeneity<0.001; p<0.001). Conclusions: This study suggested that MIF -173G/C gene polymorphism may increase increase cancer in the Chinese population.Furthermore, more larger sample and representative population-based casees and well-matched controls are needed to validate our results.

Updated Assessment of the Association of the XRCC1 Arg399Gln Polymorphism with Lung Cancer Risk in the Chinese Population

  • Yang, Hai-Yan;Yang, Si-Yu;Shao, Fu-Ye;Wang, Hai-Yu;Wang, Ya-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.495-500
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    • 2015
  • Background: Published studies have reported relationships between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and lung cancer risk in Chinese population. However, the epidemiological results remained controversial. The objective of this study was to clarify the association of XRCC1 Arg399Gln polymorphism with lung cancer risk in the Chinese population. Materials and Methods: Systematic searches were performed through the database of Medline/Pubmed, Web of Science, Embase, CNKI and WanFang Medical Online. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated to estimate the strength of the association. Results: Overall, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.36, 95%CI: 1.09-1.71) in the Chinese population on the basis of 19 studies with 5,416 cases and 5,782 controls. We did not observe any association between XRCC1 codon 399 Arg/Gln and Arg/Gln+Gln/Gln polymorphisms and lung cancer risk (OR=1.00, 95%CI: 0.92-1.08 and OR=1.05, 95%CI: 0.97-1.13, respectively). Limiting the analysis to studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.18, 95%CI: 1.01-1.38). When stratified by source of control, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Arg/Gln+Gln/Gln genotype on the basis of hospitalized patient-based controls (OR=1.21, 95%CI: 1.04-1.42) and among subjects carrying XRCC1 codon 399 Gln/Gln genotype on the basis of healthy subject-based controls (OR=1.22, 95%CI: 1.04-1.43). Conclusions: Our findings indicated that certain XRCC1 Arg399Gln variants might affect the susceptibility of lung cancer in Chinese population. Larger sample size studies are required to confirm our findings.

Gene Polymorphism of XRCC1 Arg399Gln and Cervical Carcinoma Susceptibility in Asians: A Meta-analysis Based on 1,759 Cases and 2,497 Controls

  • Liu, Yi-Ting;Shi, Jing-Pu;Fu, Ling-Yu;Zhou, Bo;Wang, Hai-Long;Wu, Xiao-Mei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.189-193
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    • 2013
  • Many epidemiological studies in Asian populations have investigated associations between the Arg399Gln gene polymorphism of X-ray repair cross complementing gene 1 (XRCC1) and risk of cervical carcinoma, but no conclusions have been available because of controversial results. Therefore a meta-analysis was conducted for clarification. Relevant studies were identified by searching the Pubmed, Embase, the Web of Science, Cochrane Collaboration's database, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and China Biological Medicinse (CBM) until September, 2012. A total of eight studies were included in the present meta-analysis, which described 1,759 cervical carcinoma cases and 2,497 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) as effect size were calculated by fixed-effect or random-effect models. The overall results indicated that the XRCC1-399G/A polymorphism was marginally associated with cervical carcinoma in Asians: OR (95%CI): 1.16 (1.07, 1.26) in the G/A vs G/G inheritance model, 1.24 (0.87, 1.76)in A/A vs G/G inheritance model, 1.13 (1.01, 1.27) in the dominant inheritance model and 1.18 (0.94, 1.47) in the recessive inheritance model. Subgroup analyses on sample size showed no significant correlation in the small-sample size group but the large-sample size group was consistent with the outcomes of overall meta-analysis. In the subgroup analysis by regions, we only found significant association under the G/A vs G/G inheritance model in the Chinese population. For the non-Chinese populations, no correlation was detected in any genetic inheritance model. In the Asian populations, XRCC1-399G/A gene polymorphism was implied to be associated with cervical carcinoma.

Prognostic Value of Matrix Metalloproteinase 9 Expression in Breast Cancer Patients: A Meta-analysis

  • Song, Jian;Su, Hong;Zhou, Yang-Yang;Guo, Liang-Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.1615-1621
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    • 2013
  • Background: Matrix metalloproteinase 9 (MMP-9) is related to tumor invasion and metastasis. However, the role of MMP-9 expression in breast cancer survival remains controversial. The purpose of this study was to accomplish a more accurate estimation of the association between MMP-9 expression and survival results in breast cancer patients through meta-analysis. Methods: A meta-analysis of published studies investigating the effects of positive MMP-9 expression on both relapse free survival (RFS) and overall survival (OS) was performed. Relevant literature was confirmed by searching electronic databases including PubMed, Ovid, EMBASE and China National Knowledge Infrastructure (CNKI) before November 1, 2012. Individual hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled HRs with 95% CIs were used to evaluate the strength of the association between positive MMP-9 expression and survival results of breast cancer patients. Funnel plot and Egger's regression tests were used to evaluate publication bias. Heterogeneity and sensitivity analysis was also conducted. All the work was completed using STATA. Results: A total of 2,344 patients from 15 evaluative studies were finally included. Pooled HRs and 95% CIs suggested that MMP-9 overexpression had an unfavorable impact on both OS (HR: 1.70, 95% CI: 1.41-2.04) and RFS (HR: 1.54, 95% CI: 1.17-2.01) in breast cancer patients. There was no significant heterogeneity observed in the studies reported for OS (P=0.360, $I^2$=8.8%), but not RFS (P=0.002, $I^2$=67%). Publication bias was absent among the studies both in OS and RFS cases (t=-0.54, P=0.605 and t=1.71, P=0.131, respectively). Omission of any single study had little effect on the combined risk estimates on sensitivity analysis. Conclusion: The results of this meta-analysis suggest that positive MMP-9 expression confers a higher risk of relapse and a worse survival in patients with breast cancer. Larger prospective studies are now needed to evaluate the clinical utility of MMP-9 expression.

PLCE1 rs2274223 Polymorphism and Susceptibility to Esophageal Cancer: a Meta-analysis

  • Guo, Li-Yan;Yang, Ning;Hu, Die;Zhao, Xia;Feng, Bing;Zhang, Yan;Zhai, Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9107-9112
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    • 2014
  • Purpose: To investigate and study the relationship between the PLCE1 rs2274223 gene polymorphism and susceptibility to esophageal cancer by meta-analysis. Materials and Methods: The literature was searched in Wanfang, CNKI, PubMed, CBM, Web of Science, MEDLINE, EMBASE, Springer, Elsevier and Cochrane databases from the date of January $1^{st}$ 2004 to April $1^{st}$ 2014 to collect case-control studies on the PLCE1 polymorphism and susceptibility to esophageal cancer. For the population genotype distributions of both esophagus cancer and control groups, their odds ratios (ORs) and 95% confidence intervals (CIs) were taken as effect indexes. Disqualified studies were excluded. Odds ratios of PLCE1 rs2274223 genotype distributions in the group of patients with esophageal cancer and the group of healthy control were calculated. The metaanalysis software, RevMan5.0, was applied for heterogeneity test, pooled OR and 95% confidence intervals. Sensitivity analysis and publication bias were also explored. Results: A total of twelve case-control studies were included, covering a total of 9, 912 esophageal cancer cases and 13, 023 controls were included. The pooled odds ratio of PLCE1 rs2274223 genotype GA vs AA was 1.29 (95%CI=1.17~1.43), p<0.01, GG vs AA was 1.65 (95%CI=1.32~2.05), p<0.01, GG/GA vs AA was 1.30 (95%CI=1.16~1.46), p<0.01 and GG vs GA/AA was 1.48 (95%CI=1.22~1.80), p<0.01. The PLCE1 rs2274223 polymorphism was thus associated with risk of esophageal cancer in all genetic models. In the stratified analysis by ethnicity, and source of controls, no significantly increased risk was observed for white persons. There was no obvious publication bias detected. Conclusions: This meta-analysis showed there was a significantly association between PLCE1 rs2274223 polymorphism and esophageal cancer in yellow race populations. Due to some minor limitations, our findings should be confirmed in further studies.