Association of IL-6 -174G>C and -572G>C Polymorphisms with Susceptibility to Cervical Cancer and Ovarian Cancer.

BACKGROUND: During the past decades, the expansion of molecular development has had a key role in understanding the basis of gynecological cancer. Interleukin-6 (IL-6) is known to be involved in the pathogenesis of different cancers. Here, we evaluated the association of IL-6 -174G>C and -572 G>C polymorphisms with susceptibility to cervical and ovarian cancers in an Iranian population. METHODS: A total of 131 cases with ovarian cancer, 124 cases with cervical cancer and 140 healthy subjects were enrolled to the study. DNA was extracted from peripheral blood cells of subjects to genotype the IL-6 -174G>C and -572 G>C polymorphisms by amplification refractory mutation system (RFLP) polymerase chain reaction (PCR). RESULTS: There was a significant association of IL-6 -174G>C CC genotype (OR= 3.231, 95% CI: 1.130-9.239, p=0.029) and C allele (OR = 1.915; 95%CI: 1.266-2.896, p=0.002) with an increased risk of ovarian cancer. Moreover, the IL-6 -174G>C CC genotype (OR= 3.162, 95% CI: 1.094-9.141, p=0.034) and C allele (OR = 1.724; 95%CI: 1.129-2.633, p=0.012) was associated with increased risk of cervical cancer. CONCLUSIONS: This study showed that the IL-6 -174G>C polymorphism was associated with ovarian cancer and cervical cancer risk. However, IL-6 -572 G>C polymorphism was not associated.

A meta-analysis for association of TNF-α -308G>A polymorphism with susceptibility to Ankylosing Spondylitis.

OBJECTIVE: We performed a meta-analysis of all eligible studies on the association of TNF-α -308G>A polymorphism with risk of Ankylosing spondylitis (AS). METHODS: A comprehensive literature research was performed in online databases. RESULTS: A total of 28 studies with 4489 cases and 5919 controls were included. Pooled ORs showed a significant association between TNF-α -308G>A polymorphism and risk of AS. Moreover, stratified analysis by ethnicity showed a significant association between TNF-α -308G>A polymorphism and AS risk in Asians, Caucasians and Mixed populations, but not in Chinese population. CONCLUSION: This meta-analysis suggested that the TNF-α -308G>A polymorphism was associated with AS risk.

Association of IL-10 -1082A>G, -819C>T, and -592C>A polymorphisms with susceptibility to chronic and aggressive periodontitis: a systematic review and meta-analysis.

OBJECTIVES: Several epidemiological studies have evaluated association of interleukin 10 (IL-10) polymorphisms with risk of periodontitis. However, the results remain conflicting and inconclusive. Here, we carried out a comprehensive systematic review and meta-analysis to evaluate the association of IL-10 -1082A>G, -819C>T, and -592C>A polymorphisms with risk of chronic (CP) and aggressive (CP) periodontitis. METHODS: Electronic databases including PubMed, Science Direct, SciELO, and CNKI were systematically searched to identify all relevant studies published up to 01 June 2020. RESULTS: A total of 60 case-control studies with 5313 cases and 6528 controls met our inclusion criteria. Overall, the pooled data showed that the IL-10 -592C>A polymorphism was statistically associated with increased risk of periodontitis in the overall population, while no significant association was identified for IL-10 -1082A>G and IL-10 -819C>T polymorphisms. The subgroup analysis by ethnicity revealed that the IL-10 -1082A>G polymorphism was significantly associated with periodontitis risk in Caucasians, IL-10 -819C>T polymorphism in mixed population, and IL-10 -592C>A polymorphism in both Asians and mixed populations. When further analyzed by periodontitis type, only the IL-10 -592C>A polymorphism was associated with CP risk, but not AgP; and the IL-10 -1082A>G and -819C>T polymorphisms have not positive association neither in the CP and AgP. CONCLUSIONS: The current meta-analysis showed that the IL-10 -592C>A polymorphism was statistically associated with periodontitis risk in the overall population. Moreover, the IL-10 -1082A>G, IL-10 -819C>T, and IL-10 -592C>A polymorphisms were associated with periodontitis risk by ethnicity. Therefore, the IL-10 polymorphisms are of high clinical relevance by ethnicity and would be a useful marker to identify patients who are at higher risk for periodontitis.

An Updated and Comprehensive Meta-Analysis of Association between VEGA -634G > C, -460T > C, +405G > C and +936C > T Polymorphisms and Retinopathy of Prematurity Risk.

BACKGROUND: Previous studies have suggested an association between VEGF-A polymorphisms and retinopathy of prematurity (ROP) risk. But the conclusions are still controversial. The aim of this meta-analysis was to evaluate the association between the VEGF-A polymorphisms and susceptibility of ROP. Methods: We searched PubMed, Scopus, WanFang and CNKI databases for all eligible case-control studies published before September 30, 2019. Results: A total of 27 case-control studies with 5,748 ROP cases and 6,146 controls were selected. The results suggested that there was an association between VEGF-A -460T > C polymorphism and increased risk of ROP under the allele model (C vs. T: OR= 0.879, 95% CI 0.776-0.994, p = 0.040). However, VEGF-A -634G > C, +405G > C and +936C > T polymorphisms were not significantly associated with risk of ROP. The subgroup analysis demonstrated that VEGF-A +405G > C polymorphism was associated with ROP risk in Caucasians. Conclusions: This meta-analysis indicates that VEGF-A -460T > C polymorphism may contribute to the susceptibility for ROP.

Association of XPG rs17655G>C and XPF rs1799801T>C Polymorphisms with Susceptibility to Cutaneous Malignant Melanoma: Evidence from a Case-Control Study, Systematic Review and Meta-Analysis

BACKGROUND: Previous studies have evaluated associations of XPG rs17655G>C and XPF rs1799801T>C polymorphisms with a risk of cutaneous malignant melanoma (CMM). However, their results thus remained inconsistent or even contradictory. Thus, the aim of this meta-analysis was to evaluate association of XPG rs17655G>C and XPF rs1799801T>C polymorphism with a risk of CMM. METHODS: A comprehensive literature search was performed on PubMed, Web of Science, Scopus, SciELO and CNKI databases up to October 15, 2019 to identify relevant studies. Moreover, a case-control study was conducted to evaluate association of XPF rs1799801T>C with CMM risk in the Iranian population. The odds ratio (OR) and 95% confidence interval (CI) values were used to estimate the strength of the associations. RESULTS: Total of 12 studies including 9 studies with 5,362 cases and 7,195 controls on XPG rs17655G>C and 3 studies with 803 CMM cases and 737 controls on XPF rs1799801T>C were selected. Pooled data revealed that XPF rs1799801T>C polymorphism was significantly associated with an increased risk of CMM under the heterozygote model (CT vs. TT: OR = 1.313; 95% CI 1.062-1.624; P = 0.012). However, XPG rs17655G>C polymorphism was not significantly associated with the risk of CMM in the overall population and by ethnicity. The subgroup analysis showed a significant association between XPG rs17655G>C polymorphism and CMM in polymerase chain reaction-based restriction fragments length polymorphism (PCR-RFLP) group of studies. CONCLUSION: This meta-analysis result revealed that XPF rs1799801T>C polymorphism may be a risk factor for developing of CMM. However, our pooled data inconsistence with the previous meta-analyses revealed that XPG rs17655G>C polymorphism was not associated with the risk of CMM.

Association of MTHFR 677C > T and 1298A > C polymorphisms with susceptibility to attention deficit and hyperactivity disorder.

Background: The associations of MTHFR polymorphisms with risk of attention deficit and hyperactivity disorder (ADHD) are poorly elucidated. This study was performed to evaluate the association of MTHFR polymorphisms with ADHD risk in Iranian children.Methods: This case-control study included 214 children with ADHD and 220 healthy subjects. The MTHFR 677C > T and 1298A > C polymorphisms were genotyped by an ABI PRISMs 7500 real-time PCR System. The odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association.Results: The MTHFR 1298A > C polymorphism CC genotype (OR= 1.526, 95% CI 1.004-2.320, p = 0.048) and C allele (OR= 1.336, 95% CI 0.1023-1.745, p = 0.034) were associated with an increased risk of ADHD. There was no significant association between MTHFR 677C > T polymorphism and increased risk of ADHD.Conclusions: Our results revealed that the MTHFR 1298A > C polymorphism but not the MTHFR 677 C > T is associated with increased risk of ADHD in Iranian children.

ASSOCIATION OF RS2435357 AND RS1800858 POLYMORPHISMS IN RET PROTO-ONCOGENE WITH HIRSCHSPRUNG DISEASE: SYSTEMATIC REVIEW AND META-ANALYSIS.

INTRODUCTION: Many published studies have estimated the association of rs2435357 and rs1800858 polymorphisms in the proto-oncogene rearranged during transfection (RET) gene with Hirschsprung disease (HSCR) risk. However, the results remain inconsistent and controversial. AIM: To perform a meta-analysis get a more accurate estimation of the association of rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene with HSCR risk. METHODS: The eligible literatures were searched by PubMed, Google Scholar, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) up to June 30, 2018. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to HSCR. RESULTS: A total of 20 studies, including ten (1,136 cases 2,420 controls) for rs2435357 and ten (917 cases 1,159 controls) for rs1800858 were included. The overall results indicated that the rs2435357 (allele model: OR=0.230, 95% CI 0.178-0.298, p=0.001; homozygote model: OR=0.079, 95% CI 0.048-0.130, p=0.001; heterozygote model: OR=0.149, 95% CI 0.048-0.130, p=0.001; dominant model: OR=0.132, 95% CI 0.098-0.179, p=0.001; and recessive model: OR=0.239, 95% CI 0.161-0.353, p=0.001) and rs1800858 (allele model: OR=5.594, 95% CI 3.653-8.877, p=0.001; homozygote model: OR=8.453, 95% CI 3.783-18.890, p=0.001; dominant model: OR=3.469, 95% CI 1.881-6.396, p=0.001; and recessive model: OR=6.120, 95% CI 3.608-10.381, p=0.001) polymorphisms were associated with the increased risk of HSCR in overall. CONCLUSIONS: The results suggest that the rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene might be associated with HSCR risk.

ASSOCIATION OF MMP-7 -181A>G POLYMORPHISM WITH COLORECTAL CANCER AND GASTRIC CANCER SUSCEPTIBILITY: A SYSTEMATIC REVIEW AND META-ANALYSIS.

INTRODUCTION: The matrix metalloproteinase-7 (MMP-7) gene -181A>G polymorphism has been reported to be associated with colorectal cancer (CRC) and gastric cancer (GC) susceptibility, yet the results of these previous results have been inconsistent or controversial. AIM: To elaborate a meta-analysis to assess the association of -181A>G polymorphism of MMP-7 with CRC and GC risk. METHODS: Published literature evaluating the association from PubMed, Web of Science, Google Scholar and other databases were retrieved up to April 25, 2018. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model. RESULTS: A total of 19 case-control studies, which included eleven studies on CRC (2,169 CRC cases and 2,346 controls) and eight studies on GC (1,545 GC cases and 2,366 controls) were identified. There was a significant association between MMP-7 -181A>G polymorphism and GC risk under the homozygote model (GG vs. AA: OR=1.672, 95% CI 1.161-2.409, p=0.006) and the recessive model (GG vs. GA+AA: OR=1.672, 95% CI 1.319-2.554, p=0.001), but not with CRC. By subgroup analysis based on ethnicity, an increased risk of CRC and GC was found only among Asians. CONCLUSIONS: This meta-analysis suggests that MMP-7 -181A>G polymorphisms is associated with GC risk, but not with CRC. However, our results clearly showed that the MMP-7 -181A>G polymorphism significantly increased the risk of CRC only in Asians.

Association of MTHFR 677C>T Polymorphism with Susceptibility to Ovarian and Cervical Cancers: A Systematic Review and Meta-Analysis.

Background: Previous studies have evaluated the impact of MTHFR 677C>T polymorphism on susceptibility to ovarian and cervical cancers in women, but the conclusions are still controversial. To get a more precise evaluation of the association between MTHFR 677C>T polymorphism and risk of ovarian and cervical cancers, we performed a meta-analysis of the association of all eligible studies. Methods: A comprehensive search performed in PubMed, Google Scholar, CNKI, and Web of Science databases to identify the relevant studies up to October 15, 2018. The strength of the association was estimated by odds ratios (OR) with 95% confidence interval (CI). Results: A total of 27 case-control studies including eleven studies with 4990 cases 7730 controls on ovarian cancer and 16 studies with 4990 cases and 7730 controls on cervical cancer were selected. Pooled data revealed that the MTHFR 677C>T polymorphism not significantly associated with an increased risk of ovarian and cervical cancers under all five genetic models. However, stratified analysis by ethnicity showed that the MTHFR 677C>T polymorphism was significantly associated with risk of ovarian cancer in Asians. No publication bias was found in the current meta-analysis. Conclusions: The results of this meta-analysis proposes that the MTHFR 677C>T polymorphism may not play a role in development of ovarian and cervical cancers in overall population. Further well-designed studies are necessary to clarify the precise role of the MTHFR 677C>T polymorphism on ovarian and cervical cancers risk.

Association of MTHFR C677T and A1298C Polymorphisms with Glaucoma Risk: a Systematic Review Meta-Analysis based 42 Case-Control Studies.

Aim: Several epidemiological studies have been performed to explore the association of MTHFR polymorphisms with glaucoma risk. However, the results were inconsistent or even inconclusive. Hence, we performed a meta-analysis to evaluate the association of MTHFR C677T and A1298C polymorphisms with glaucoma risk. Methods: A comprehensive literature search on PubMed, Google Scholar, EMBASE, and CNKI databases was performed to find all eligible studies up to January 30, 2019. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of such association. Results: A total of 42 case-control studies including 33 studies for MTHFR C677T and nine studies for A1298C polymorphism were selected. Pooled results showed that there was no significant association between the MTHFR C677T polymorphism and glaucoma risk. Similarly, no associations were found in subgroup analysis based on ethnicity and glaucoma type. However, there was a significant association between the A1298C polymorphism and the increased risk of glaucoma under heterozygote model (OR=0.765, 95% CI=0.626-0.935, P=0.009). Moreover, the significant association between MTHFR A1298C polymorphism and glaucoma were found by ethnicity and primary open angle glaucoma (POAG). Conclusions: The present meta-analysis revealed that MTHFR A1298C polymorphism is significantly associated with the increased risk of glaucoma, but not MTHFR C677T polymorphism.

Association of GSTM1, GSTT1, GSTM3, and GSTP1 Genes Polymorphisms with Susceptibility to Osteosarcoma: a Case- Control Study and Meta-Analysis

Background: Some studies have investigated the association of GSTM1, GSTT1, GSTM3, and GSTP1 polymorphisms with susceptibility to osteosarcoma; however, these studies results are inconsistent and inconclusive. In order to drive a more precise estimation, the present case-control study and meta-analysis was performed to investigate association of GSTM1, GSTT1, GSTM3, and GSTP1 polymorphisms with osteosarcoma. Methods: Eligible articles were identified by a search of several electronic databases for the period up to May 5, 2018. Odds ratios were pooled using either fixed-effects or random effects models. Results: Finally, a total of 24 case-control studies with 2,405 osteosarcoma cases and 3,293 controls were included in the present meta-analysis. Overall, significantly increased osteosarcoma risk was found when all studies were pooled into the meta-analysis of GSTT1 (Null vs. Present: OR= 1.247 95% CI 1.020-1.524, P= 0.031) and GSTP1 polymorphism (B vs. A: OR= 8.899 95% CI 2.722-29.094, P≤0.001). In the stratified, significantly increased osteosarcoma risk was observed for GSTT1 polymorphism among Asians (Null vs. Present: OR= 1.300 95% CI 1.034-1.635, P= 0.025), but not among Caucasians. Conclusions: This meta-analysis demonstrated that GSTP1 and GSTT1 null genotype are associated with the risk of osteosarcoma. Future large welldesigned epidemiological studies are warranted to validate our results.

ASSOCIATION OF INTERLEUKIN-10 -592A>C AND -819T>C POLYMORPHISMS WITH GASTRIC CANCER RISK: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 44 CASE-CONTROL STUDIES.

INTRODUCTION: A series of studies have evaluated the association between -592A>C and -819T>C polymorphisms in the promoter regions of Interleukin-10 (IL-10) and gastric cancer (GC) risk. However, the results remain inconclusive. OBJECTIVE: To better understand the association of the polymorphisms with GC risk, we performed a comprehensive meta-analysis. METHOD: An electronic search was performed of several databases to identify relevant studies up to April 2018. RESULTS: A total of 44 case-control studies, including 26 studies on IL-10 -592A>C (5,332 cases and 8,272 controls) and 18 studies on IL-10 -819T>C (3,431 cases and 6,109 controls) were selected. Overall, -592A>C polymorphism was associated with the risk of GC under the heterozygote model (OR=1.153, 95% CI=1.020-1.305, p=0.023), but not -819T>C polymorphism. When stratified by ethnicity, significant association was only observed in the Asians under the allele model (OR=1.153, 95% CI=1.007-1.320, p=0.040) and the heterozygote model (OR=1.218, 95% CI=1.076-1.379, p=0.002) for -592A>C. CONCLUSION: The current meta-analysis results inconsistent with previous meta-analyses; showed that the IL-10 -592A>C polymorphism, but not -819T>C polymorphism, may be contributed to the susceptibility of GC in overall and Asian populations.

Association of mmp-7 -181A>G polymorphism with colorectal cancer and gastric cancer susceptibility: a systematic review and meta-analysis / Associação do polimorfismo mmp-7 -181a>G com câncer colorretal e suscetibilidade ao câncer gástrico: revisão sistemática e metanálise

ABSTRACT Introduction: The matrix metalloproteinase-7 (MMP-7) gene -181A>G polymorphism has been reported to be associated with colorectal cancer (CRC) and gastric cancer (GC) susceptibility, yet the results of these previous results have been inconsistent or controversial. Aim: To elaborate a meta-analysis to assess the association of -181A>G polymorphism of MMP-7 with CRC and GC risk. Methods: Published literature evaluating the association from PubMed, Web of Science, Google Scholar and other databases were retrieved up to April 25, 2018. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model. Results: A total of 19 case-control studies, which included eleven studies on CRC (2,169 CRC cases and 2,346 controls) and eight studies on GC (1,545 GC cases and 2,366 controls) were identified. There was a significant association between MMP-7 -181A>G polymorphism and GC risk under the homozygote model (GG vs. AA: OR=1.672, 95% CI 1.161-2.409, p=0.006) and the recessive model (GG vs. GA+AA: OR=1.672, 95% CI 1.319-2.554, p=0.001), but not with CRC. By subgroup analysis based on ethnicity, an increased risk of CRC and GC was found only among Asians. Conclusions: This meta-analysis suggests that MMP-7 -181A>G polymorphisms is associated with GC risk, but not with CRC. However, our results clearly showed that the MMP-7 -181A>G polymorphism significantly increased the risk of CRC only in Asians.

RESUMO Introdução: O polimorfismo da matriz metaloproteinase-7 (MMP-7) -181A>G tem sido relatado como associado à suscetibilidade dos cânceres colorretal (CRC) e gástrico (GC), mas os resultados desses estudos anteriores foram inconsistentes ou controversos. Objetivo: Elaborar metanálise para avaliar a associação do polimorfismo -181A> G da MMP-7 com o risco de CRC e GC. Métodos: Revisão da literatura publicada avaliando essa associação no PubMed, Web of Science, Google Acadêmico e outras bases de dados até 25 de abril de 2018. Odds ratio (OR) e o intervalo de confiança de 95% (IC) foram calculados usando dados aleatórios ou modelo de efeitos fixos. Resultados: Um total de 19 estudos caso-controle, que incluíram 11 trabalhos sobre CRC (2.169 casos de CCR e 2.346 controles) e oito sobre GC (1.545 casos de GC e 2.366 controles) foram identificados. Houve associação significativa entre o polimorfismo MMP-7 -181A>G e o risco de GC sob o modelo homozigoto (GG vs. AA: OR=1,672, IC 95% 1,161-2,409, p=0,006) e o modelo recessivo (GG vs. GA + AA: OR=1,672, IC 95% 1,319-2,554, p=0,001), mas não com CRC. Por análise de subgrupos com base na etnia, um risco aumentado de CRC e GC foi encontrado apenas entre os asiáticos. Conclusões: Esta metanálise sugere que os polimorfismos MMP-7 -181A>G estão associados ao risco de GC, mas não ao CRC. No entanto, estes resultados mostraram claramente que o polimorfismo MMP-7 -181A>G aumentou significativamente o risco de CRC apenas em asiáticos.

Association of rs2435357 and rs1800858 polymorphisms in ret proto-oncogene with hirschsprung disease: systematic review and meta-analysis / Associação dos polimorfismos rs2435357 e rs1800858 no proto-oncogene ret com doença de hirschsprung: revisão sistemática e metanálise

ABSTRACT Introduction: Many published studies have estimated the association of rs2435357 and rs1800858 polymorphisms in the proto-oncogene rearranged during transfection (RET) gene with Hirschsprung disease (HSCR) risk. However, the results remain inconsistent and controversial. Aim: To perform a meta-analysis get a more accurate estimation of the association of rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene with HSCR risk. Methods: The eligible literatures were searched by PubMed, Google Scholar, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) up to June 30, 2018. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to HSCR. Results: A total of 20 studies, including ten (1,136 cases 2,420 controls) for rs2435357 and ten (917 cases 1,159 controls) for rs1800858 were included. The overall results indicated that the rs2435357 (allele model: OR=0.230, 95% CI 0.178-0.298, p=0.001; homozygote model: OR=0.079, 95% CI 0.048-0.130, p=0.001; heterozygote model: OR=0.149, 95% CI 0.048-0.130, p=0.001; dominant model: OR=0.132, 95% CI 0.098-0.179, p=0.001; and recessive model: OR=0.239, 95% CI 0.161-0.353, p=0.001) and rs1800858 (allele model: OR=5.594, 95% CI 3.653-8.877, p=0.001; homozygote model: OR=8.453, 95% CI 3.783-18.890, p=0.001; dominant model: OR=3.469, 95% CI 1.881-6.396, p=0.001; and recessive model: OR=6.120, 95% CI 3.608-10.381, p=0.001) polymorphisms were associated with the increased risk of HSCR in overall. Conclusions: The results suggest that the rs2435357 and rs1800858 polymorphisms in the RET proto-oncogene might be associated with HSCR risk.

RESUMO Introdução: Muitos estudos publicados estimaram a associação dos polimorfismos rs2435357 e rs1800858 do proto-oncogene rearranjado durante a transfecção (RET) com o risco de doença por Hirschsprung (HSCR). No entanto, os resultados permanecem inconsistentes e controversos. Objetivo: Realizar metanálise para obter estimativa mais precisa da associação dos polimorfismos rs2435357 e rs1800858 no proto-oncogene RET com risco de HSCR. Método: A literatura elegível foi pesquisada pelo PubMed, Google Scholar, EMBASE e CNKI até 30 de junho de 2018. Resultados: Um total de 20 estudos, incluindo dez (1.136 casos 2.420 controles) para rs2435357 e dez (917 casos 1.159 controles) para rs1800858 foram incluídos. Os resultados globais indicaram que o rs2435357 (modelo alelo: OR=0,230, IC 95% 0,178-0,298, p=0,001; modelo homozigoto: OR=0,079, IC 95% 0,048-0,130, p=0,001; modelo heterozigoto: OR=0,149 , IC 95% 0,048-0,130, p=0,001, modelo dominante: OR=0,132, IC 95% 0,098-0,179, p=0,001 e modelo recessivo: OR=0,239, IC 95% 0,161-0,353, p=0,001) e rs1800858 (modelo alelo: OR=5,594, IC 95% 3,653-8,877, p=0,001; modelo homozigoto: OR=8,453, IC 95% 3,783-18,890, p=0,001; modelo dominante: OR=3,469, IC 95% 1,881- 6,396, p=0,001 e modelo recessivo: OR=6,120, 95% CI 3,608-10,381, p=0,001) polimorfismos foram associados com o aumento do risco de HSCR em geral. Conclusões: Os resultados sugerem que os polimorfismos rs2435357 e rs1800858 no proto-oncogene RET podem estar associados ao HSCR.

Association of interleukin-10 -592a>c and -819t>c polymorphisms with gastric cancer risk: a systematic review and meta-analysis of 44 case-control studies / Associação de polimorfismos da interleucina-10 -592 a>c e -819 t> c com risco de câncer gástrico: revisão sistemática e metanálise de 44 estudos de caso-controle

ABSTRACT Introduction: A series of studies have evaluated the association between -592A>C and -819T>C polymorphisms in the promoter regions of Interleukin-10 (IL-10) and gastric cancer (GC) risk. However, the results remain inconclusive. Objective: To better understand the association of the polymorphisms with GC risk, we performed a comprehensive meta-analysis. Method: An electronic search was performed of several databases to identify relevant studies up to April 2018. Results: A total of 44 case-control studies, including 26 studies on IL-10 -592A>C (5,332 cases and 8,272 controls) and 18 studies on IL-10 -819T>C (3,431 cases and 6,109 controls) were selected. Overall, -592A>C polymorphism was associated with the risk of GC under the heterozygote model (OR=1.153, 95% CI=1.020-1.305, p=0.023), but not -819T>C polymorphism. When stratified by ethnicity, significant association was only observed in the Asians under the allele model (OR=1.153, 95% CI=1.007-1.320, p=0.040) and the heterozygote model (OR=1.218, 95% CI=1.076-1.379, p=0.002) for -592A>C. Conclusion: The current meta-analysis results inconsistent with previous meta-analyses; showed that the IL-10 -592A>C polymorphism, but not -819T>C polymorphism, may be contributed to the susceptibility of GC in overall and Asian populations.

RESUMO Introdução: Uma série de estudos avaliou a associação entre os polimorfismos -592A>C e -819T>C nas regiões promotoras do risco de interleucina-10 (IL-10) e câncer gástrico (GC). No entanto, os resultados permanecem inconclusivos. Objetivo: Para entender melhor a associação dos polimorfismos com o risco de GC, realizamos uma meta-análise abrangente. Método: Foi realizada busca eletrônica de vários bancos de dados para identificar estudos relevantes até abril de 2018. Resultados: Um total de 44 estudos caso-controle, incluindo 26 estudos sobre IL-10 -592A>C (5.332 casos e 8.272 controles) e 18 estudos sobre IL-10 -819T>C (3.431 casos e 6.109 controles) foram selecionados. No geral, o polimorfismo -592A> C foi associado ao risco de GC sob o modelo heterozigoto (OR=1,153, 95% IC=1,020-1,305, p=0,023), mas não polimorfismo -819T>C. Quando estratificada por etnia, associação significativa foi observada apenas nos asiáticos sob o modelo alelo (OR=1,153, IC 95%=1,007-1,320, p=0,040) e o modelo heterozigoto (OR=1,218, IC 95%=1,076-1,379, p=0,002) para -592A>C. Conclusão: Os atuais resultados são inconsistentes com metanálises anteriores; mostrou que o polimorfismo IL-10 -592A> C, mas não o polimorfismo -819T>C, pode ter contribuído para a suscetibilidade de GC em populações globais e asiáticas.

Association of IL-10 rs1800871 and rs1800872 Polymorphisms with Breast Cancer Risk: A Systematic Review and Meta-Analysis

Background: The rs1800871 and rs1800872 polymorphisms of interleukin 10 (IL-10) gene has been indicated to be associated with breast cancer (BC) risk, but study results are still debatable. To derive a more precise evaluation, we performed a comprehensive meta-analysis. Methods: Multiple electronic databases were searched to identify studies assessing the IL-10 rs1800871 and rs1800872 polymorphisms with BC risk. Results: A total of 21 case-control studies with 6054 cases and 6355 controls were included in this met-analysis. There was a significant association between the rs1800871 polymorphism and BC risk (CT vs. TT: OR= 1.17, 95% CI 1.01-1.35, p=0.02; and CC+CT vs. TT: OR= 1.29, 95% CI 1.00-1.66, p=0.04). Moreover, increased BC risks were also associated with the rs1800872 polymorphism (C vs. A: OR= 1.29, 95% CI 1.04-1.60, p=0.01; CC vs. AA: OR= 1.54, 95% CI 1.03-2.30, p=0.03; CC+CA vs. AA: OR= 1.43, 95% CI 1.01-2.01, p=0.03; and CC vs. CA+AA: OR= 1.23, 95% CI 1.01-1.51, p=0.04). A pooling of the studies was also conducted by ethnicity, but failed to show an association of IL-10 rs1800871 and rs1800872 polymorphism with BC risk in Asians and Caucasians. Conclusions: Our results are inconsistent with previous meta-analysis suggests that IL-10 rs1800871 and rs1800872 polymorphisms might contribute to BC susceptibility in overall population, but not by ethnicity.

Relevance of hMLH1 -93G>A, 655A>G and 1151T>A polymorphisms with colorectal cancer susceptibility: a meta-analysis based on 38 case-control studies.

OBJECTIVE: There has been increasing interest in the study of the association between human mutL homolog 1 (hMLH1) gene polymorphisms and risk of colorectal cancer (CRC). However, results from previous studies are inconclusive. Thus, a meta-analysis was conducted to derive a more precise estimation of the effects of this gene. METHODS: A comprehensive search was conducted in the PubMed, EMBASE, Chinese Biomedical Literature databases until January 1, 2018. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. RESULTS: Finally, 38 case-control studies in 32 publications were identified met our inclusion criteria. There were 14 studies with 20668 cases and 19533 controls on hMLH1 -93G>A, 11 studies with 5,786 cases and 8,867 controls on 655A>G and 5 studies with 1409 cases and 1637 controls on 1151T>A polymorphism. The combined results showed that 655A>G and 1151T>A polymorphisms were significantly associated with CRC risk, whereas -93G>A polymorphism was not significantly associated with CRC risk. As for ethnicity, -93G>A and 655A>G polymorphisms were associated with increased risk of CRC among Asians, but not among Caucasians. More interestingly, subgroup analysis indicated that 655A>G might raise CRC risk in PCR-RFLP and HB subgroups. CONCLUSION: Inconsistent with previous meta-analyses, this meta-analysis shows that the hMLH1 655A>G and 1151T>A polymorphisms might be risk factors for CRC. Moreover, the -93G>A polymorphism is associated with the susceptibility of CRC in Asian population.

ASSOCIATION OF PROMOTER REGION POLYMORPHISMS OF INTERLEUKIN-10 GENE WITH SUSCEPTIBILITY TO COLORECTAL CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Several epidemiological studies have investigated the association of promoter region polymorphisms of Interleukin-10 (IL-10) gene with colorectal cancer (CRC), while the conclusion is still conflicting and inconclusive. OBJECTIVE: We conducted this meta-analysis to evaluate the association of promoter region polymorphisms of IL-10 with CRC. METHODS: Eligible articles were identified by a search of several bibliographic databases for the period up to March 15, 2018. The strength of the association was measured by odd ratios with 95% confidence intervals. RESULTS: A total of 28 case-control studies with 5,647 CRC cases and 6,908 controls were selected, including 14 studies for IL-10 -1082A>G (rs1800896) polymorphism (2,702 cases and 3,649 controls), eleven studies for -592C>A (rs1800872) polymorphism (3,259 cases and 4,992 controls), and three studies for -819T>C (rs1800871) polymorphism (477 cases and 544 controls). By pooling all eligible studies, we found that the IL-10 -1082A>G and -592C>A polymorphisms were not associated with increased CRC risk in overall population. However, there was significant associations between the IL-10 -819T>C polymorphism and CRC susceptibility under the allele model (A vs G: OR=1.278, 95% CI 1.043-1.566, P=0.018) and the recessive model (AA vs AG+GG: OR=1.709, 95% CI 1.026-2.845, P=0.039). CONCLUSION: In this meta-analysis we found that IL-10 -819T>C polymorphism was associated with significantly increased risk of CRC; while the IL-10 -1082A>G and -592C>A polymorphisms were not associated with CRC risk. The IL-10 -819T>C polymorphism may be important as suspected predictive factor of CRC occurrence.

Relevance of hMLH1 -93G>A, 655A>G and 1151T>A polymorphisms with colorectal cancer susceptibility: a meta-analysis based on 38 case-control studies

SUMMARY OBJECTIVE: There has been increasing interest in the study of the association between human mutL homolog 1 (hMLH1) gene polymorphisms and risk of colorectal cancer (CRC). However, results from previous studies are inconclusive. Thus, a meta-analysis was conducted to derive a more precise estimation of the effects of this gene. METHODS: A comprehensive search was conducted in the PubMed, EMBASE, Chinese Biomedical Literature databases until January 1, 2018. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. RESULTS: Finally, 38 case-control studies in 32 publications were identified met our inclusion criteria. There were 14 studies with 20668 cases and 19533 controls on hMLH1 −93G>A, 11 studies with 5,786 cases and 8,867 controls on 655A>G and 5 studies with 1409 cases and 1637 controls on 1151T>A polymorphism. The combined results showed that 655A>G and 1151T>A polymorphisms were significantly associated with CRC risk, whereas −93G>A polymorphism was not significantly associated with CRC risk. As for ethnicity, −93G>A and 655A>G polymorphisms were associated with increased risk of CRC among Asians, but not among Caucasians. More interestingly, subgroup analysis indicated that 655A>G might raise CRC risk in PCR-RFLP and HB subgroups. CONCLUSION: Inconsistent with previous meta-analyses, this meta-analysis shows that the hMLH1 655A>G and 1151T>A polymorphisms might be risk factors for CRC. Moreover, the −93G>A polymorphism is associated with the susceptibility of CRC in Asian population.

RESUMO OBJETIVO: Tem havido crescente interesse no estudo da associação entre polimorfismos do gene mutL homólogo 1 humano (hMLH1) e risco de câncer colorretal (CRC). No entanto, os resultados de estudos anteriores não são conclusivos. Assim, uma meta-análise foi conduzida para obter uma estimativa mais precisa dos efeitos desse gene. MÉTODOS: Uma pesquisa abrangente foi realizada nas bases de dados PubMed, Embase, Chinese Biomedical Literature até 10 de janeiro de 2018. Odds ratio (OR) com 95% de intervalo de confiança (IC) foi utilizado para avaliar a força da associação. RESULTADOS: Finalmente, foram identificados 38 estudos de casos e controles em 32 publicações, atendendo aos nossos critérios de inclusão. Houve 14 estudos com 20.668 casos e 19.533 controles em hMLH1 −93G>A, 11 estudos com 5.786 casos e 8.867 controles em 655A>G e cinco estudos com 1.409 casos e 1.637 controles em 1151T>Um polimorfismo. Os resultados combinados mostraram que os polimorfismos 655A>G e 1151T>A estavam significativamente associados ao risco de CRC, enquanto que o polimorfismo −93G>A não estava significativamente associado ao risco de CRC. Quanto à etnia, os polimorfismos de −93G>A e 655A>G foram associados ao risco aumentado de CRC entre os asiáticos, mas não entre os caucasianos. Mais interessante, a análise de subgrupos indicou que 655A>G pode aumentar o risco de CRC em subgrupos PCR-RFLP e HB. CONCLUSÃO: Inconsistente com a meta-análise anterior, esta meta-análise mostra que os polimorfismos hMLH1 655A>G e 1151T>A podem ser fatores de risco para CRC. Além disso, o polimorfismo −93G>A está associado à susceptibilidade do CRC na população asiática.

Associação de polimorfismos da região do promotor do gene interleucina-10 com susceptibilidade ao câncer colorretal: uma revisão sistemática e meta-análise / Association of promoter region polymorphisms of interleukin-10 gene with susceptibility to colorectal cancer: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Several epidemiological studies have investigated the association of promoter region polymorphisms of Interleukin-10 (IL-10) gene with colorectal cancer (CRC), while the conclusion is still conflicting and inconclusive. OBJECTIVE: We conducted this meta-analysis to evaluate the association of promoter region polymorphisms of IL-10 with CRC. METHODS: Eligible articles were identified by a search of several bibliographic databases for the period up to March 15, 2018. The strength of the association was measured by odd ratios with 95% confidence intervals. RESULTS: A total of 28 case-control studies with 5,647 CRC cases and 6,908 controls were selected, including 14 studies for IL-10 -1082A>G (rs1800896) polymorphism (2,702 cases and 3,649 controls), eleven studies for -592C>A (rs1800872) polymorphism (3,259 cases and 4,992 controls), and three studies for -819T>C (rs1800871) polymorphism (477 cases and 544 controls). By pooling all eligible studies, we found that the IL-10 -1082A>G and -592C>A polymorphisms were not associated with increased CRC risk in overall population. However, there was significant associations between the IL-10 -819T>C polymorphism and CRC susceptibility under the allele model (A vs G: OR=1.278, 95% CI 1.043-1.566, P=0.018) and the recessive model (AA vs AG+GG: OR=1.709, 95% CI 1.026-2.845, P=0.039). CONCLUSION: In this meta-analysis we found that IL-10 -819T>C polymorphism was associated with significantly increased risk of CRC; while the IL-10 -1082A>G and -592C>A polymorphisms were not associated with CRC risk. The IL-10 -819T>C polymorphism may be important as suspected predictive factor of CRC occurrence.

RESUMO CONTEXTO: Vários estudos epidemiológicos têm investigado a associação de polimorfismo da região promotora do gene interleucina-10 (IL-10) com câncer colorretal (CRC), mas por enquanto a conclusão ainda é conflitante e inconclusiva. OBJETIVO: Foi realizada esta meta-análise para avaliar a associação de polimorfismo da região promotora do Il-10 com o câncer colorretal. MÉTODOS: Os artigos elegíveis foram identificados por uma pesquisa de várias bases de dados bibliográficas para o período até 15 de março de 2018. A força da associação foi medida por odds ratio (OR) com intervalos de 95% de confiança (IC). RESULTADOS: Um total de 28 estudos de casos-controles com 5.647 casos de câncer colorretal e 6.908 controles foram selecionados, incluindo 14 estudos para o polimorfismo de IL-10-1082A>G (rs1800896) (2.702 casos e 3.649 controles), 11 estudos para-592C>A (rs1800872) polimorfismo (3.259 casos e 4.992 controles), e três estudos para-819T>C (rs1800871) polimorfismo (477 casos e 544 controles). Ao reunir todos os estudos elegíveis, verificou-se que o Il-10-1082A>G e-592C>A polimorfismo não foram associados com o aumento do risco de câncer colorretal na população global. No entanto, houve associações significativas entre o polimorfismo IL-10-819T>C e a susceptibilidade de câncer colorretal o modelo alelo (A vs G: OR=1,278; 95% CI 1,043-1,566; P=0,018) e o modelo recessivo (AA vs AG + GG: ou =1,709; 95% CI 1,026-2,845; P=0,039). CONCLUSÃO: Nesta meta-análise revelou-se que o polimorfismo IL-10-819T>C foi associado a um risco significativamente maior de câncer colorretal; enquanto o Il-10-1082A>G e-592C>A polimorfismos não foram associados com o risco de câncer colorretal. O polimorfismo IL-10-819T>C pode ser importante como fator preditivo suspeito da ocorrência de câncer colorretal.