Association Between miR-146a rs2910164 Polymorphism and Breast Cancer Susceptibility: An Updated Meta-Analysis of 9545 Cases and 10030 Controls.

BACKGROUND: Several studies have reported a possible association of miR-146a rs2910164 polymorphism with Breast Cancer (BC) development. However, the correlation between this polymorphism and susceptibility to BC is under debate. The current meta-analysis was designed and performed to more conclusively evaluate the miR-146a rs2910164 polymorphism and its potential link to BC. METHODS: Our team has selected eligible studies (published up to October 2, 2020) from several electronic databases, including Web of Science, PubMed, Scopus and Google Scholar. A total number of 9,545 BC cases and 10,030 controls extracted from 26 eligible articles were included in this study. We utilized pooled Odds Ratios (ORs) as well as 95% confidence intervals (95% CIs) under five genetic models for quantitative estimation of any possible association between miR-146a rs2910164 polymorphism and BC. RESULTS: Based on this meta-analysis, our findings suggest that there is no significant association between miR-146a rs2910164 polymorphism and BC risk. However, stratified analysis revealed that the rs2910164 polymorphism significantly increased the risk of BC in hospital-based studies using the homozygous genetic model (OR=1.37, 95%CI=1.01-1.86, p=0.043, CC vs. GG). Neither Asian nor Caucasian populations showed any significant association between rs2910164 polymorphism and BC susceptibility. CONCLUSION: In summary, our findings suggest that BC development is not associated with miR-146a rs2910164 polymorphism. However, larger ingenious future investigations might be needed for a more precise estimation of any association between miR-146a rs2910164 polymorphism and BC.

Methylation of TGM-3 Promoter and Its Association with Oral Squamous Cell Carcinoma (OSCC).

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) is among the ten most common cancers worldwide. Hypermethylation of CpG sites in the promoter region and subsequent down-regulation of a tumor suppressor gene, TGM-3 has been proposed to be linked to different types of human cancers including OSCC. In this study, methylation status of CpG sites in the promoter region of TGM-3 has been evaluated in a cohort of patients with OSCC compared to normal controls. METHODS: Forty fresh tissue samples were obtained from newly diagnosed OSCC patients and normal individuals referred to dentistry clinic for tooth extraction. DNA was extracted, bisulfite conversion was performed and it was subjected to PCR using bisulfite-sequencing PCR (BSP) primers. Prepared samples were sequenced on a DNA analyzer with both forward and reverse primers of the region of interest. The peak height values of cytosine and thymine were calculated and methylation levels for each CpG site within the DNA sequence was quantified. RESULTS: Quantitative DNA methylation analyses in CpG islands revealed that it was significantly higher in OSCC patients compared to controls. DNA methylation at CpG1/CpG3/CpG5 (p=0.004-0.01) and CpG1/CpG3 (p=0.001-0.019) sites was associated with tumor stage and grade, respectively. Male OSCC patients had higher methylation rate at CpG3 (p=0.032), while smoker patients showed higher methylation rate at CpG6 (p=0.045). CONCLUSION: These results manifested the contribution of DNA methylation of TGM-3 in OSCC and its potential association with clinico-pathologic parameters in OSCC.

An updated meta-analysis of the association between fibroblast growth factor receptor 4 polymorphisms and susceptibility to cancer.

Fibroblast growth factor receptor 4 (FGFR4) is a cell surface receptor tyrosine kinases (RTKs) for FGFs. Several studies have focused on the association between FGFR4 polymorphisms and cancer development. This meta-analysis aimed to estimate the association between FGFR4 rs351855 (Gly388Arg), rs1966265 (Val10Ile), rs7708357, rs2011077, and rs376618 polymorphisms and cancer risk. Eligible studies were identified from electronic databases. All statistical analyses were achieved with the STATA 14.0 software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantitatively estimate the association. Overall, no significant association was found among rs351855, rs2011077, and rs376618 polymorphisms with the risk of overall cancer. The rs1966265 polymorphism significantly decreased the risk of cancer in recessive (OR = 0.87, 95% CI = 0.78-0.97, P=0.009, TT vs CT+CC) genetic model. Whereas the rs7708357 polymorphism was positively associated with cancer risk in dominant (OR = 1.17, 95% CI = 1.02-1.36, P=0.028) genetic model. Stratified analysis revealed that rs351855 variant significantly increased the risk of prostate cancer in heterozygous (OR = 1.16, 95% CI = 1.02-1.32, P=0.025 AG vs GG), dominant (OR = 1.20, 95% CI = 1.06-1.35, P=0.004, AG+AA vs GG), and allele (OR = 1.22, 95% CI = 1.06-1.41, P=0.005, A vs G) genetic models. In summary, the findings of this meta-analysis indicate that rs1966265, rs7708357, and rs351855 polymorphisms are correlated to cancer development. Further well-designed studies are necessary to draw more precise conclusions.

Association between IL-27 Gene Polymorphisms and Cancer Susceptibility in Asian Population: A Meta-Analysis.

BACKGROUND: Interleukin 27 (IL-27) has potent antitumor activity. Several epidemiological studies have designated that genetic variants of the IL-27 gene may contribute to various cancer susceptibility, but the data were inconclusive.  Objective: The current meta-analysis aimed to address the association between IL-27 rs153109, rs17855750, and rs181206 polymorphisms and the risk of cancer. DATA SOURCES: Our team has selected eligible studies up to May 1, 2020, from several electronic databases, including Web of Science, PubMed, Scopus, and Google Scholar databases. RESULTS: Our meta-analysis revealed that the carriers rs153109 A>G polymorphism in the IL-27 gene have higher risks of diseases in the heterozygous (OR=1.26, 95%CI=1.06-1.49, P=0.007, AG vs AA), homozygous (OR=1.18, 95%CI=1.01-1.37, p=0.33, GG vs AA), dominant (OR=1.25, 95%CI=1.07-1.47, P=0.006, AG+GG vs AA), and allele (OR=1.15, 95%CI=1.04-1.27, P=0.008, G vs A) genetic models. Stratified analysis by cancer type indicated that this variant was significantly associated with gastrointestinal cancer, colorectal cancer and breast cancer. The findings did not support an association between rs17855750 T>G, rs181206 T>C polymorphisms of IL-27 and cancer risk. CONCLUSION: the current study findings suggest that IL-27 rs153109 polymorphism significantly increased the risk of cancer susceptibility. Well-designed replication in a larger independent genetic association study with larger sample sizes in diverse ethnicities is required to verify the findings. 

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Genetic association between HOTAIR gene and the risk of cancer: an updated meta-analysis.

Several recent investigations show that HOX transcript antisense intergenic RNA (HOTAIR) play an important role in the pathogenesis of different cancers. HOTAIR polymorphisms has been widely studied in the context of association between with the risk of cancer pathogenesis. However, there is no certain conclusion about the role of HOTAIR polymorphisms in different cancer initiation and progression. Our team has selected eligible studies up to 1 May 2019, from several electronic databases, including Web of Science, PubMed, Scopus, and Google Scholar databases. We have included total number of 102 case-control investigations extracted from 41 eligible articles for the current meta-analysis. We calculated pooled odds ratio (ORs) with their corresponding 95% confidence intervals (CIs) using either fixed-effect or random-effect models for quantitative evaluation of the strength for the association between HOTAIR gene polymorphisms and the risk of cancer. Our current meta-analysis investigation showed that HOTAIR rs4759314 polymorphism particularly increased the overall risk of cancer in different models including homozygous, recessive and allele genetic. HOTAIR rs920778 significantly raised the cancer risk only in recessive genetic model. HOTAIR rs12826786 polymorphism was associated with cancer development in heterozygous, homozygous, dominant, recessive and allele genetic models. Also, an increase in cancer risk was observed with rs874945 polymorphism of HOTAIR gene in heterozygous, dominant and allele genetic models. The rs12427129 polymorphism showed correlation with cancer susceptibility only in recessive model. Subgroup analysis based on cancer type suggested that rs4759314 polymorphism significantly increased the risk of gastric and cervical cancers, and the rs920778 polymorphism increased the risk of gastrointestinal, cervical and gastric cancers. In summary, this study found that HOTAIR polymorphisms are significantly associated with cancer development.

Association of CASP8 polymorphisms and cancer susceptibility: A meta-analysis.

Caspase-8 plays is an essential enzyme in apoptosis pathway. Several investigation have been done to identify the relation between CASP8 polymorphisms and different human cancers, but, the findings are still debated. The aim of the current investigation is to assess if CASP8 rs3834129 (-652 6N insertion/deletion), rs1045485 G > C, rs3769818 G > A, rs6723097 A > C, rs3769821 T > C, rs13113 T > A, rs3769825 G > A, rs2293554 A > C, and rs10931936 C > T polymorphisms are linked to susceptibility of cancer. Our team has extracted the eligible studies up to July 4, 2019, from different sources. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were estimated to quantitatively evaluate the association between CASP8 polymorphisms and cancer susceptibility. Our results showed that the rs3834129 and rs1045485 polymorphisms meaningfully reduced the risk of cancer, while the rs3769818, rs3769821 and rs3769825 polymorphisms considerably increased cancer susceptibility. No association of rs6723097, rs13113, rs2293554 and rs10931936 polymorphisms was observed with cancer susceptibility. The CASP8 rs3834129 polymorphism reduced the risk of gastrointestinal, digestive tract, colorectal, breast and lung cancers. Furthermore, the cancer risk was decreased in Asian and Caucasian populations as well as population- and hospital-based studies due to this polymorphism. There was not any relation between this gene polymorphism and the risk of prostate and cervical cancer development. Regarding the CASP8 rs1045485 polymorphism, the reduced breast cancer risk along with the risk of cancer in Caucasians, population- and hospital-based studies were observed.

LMO1 polymorphisms and the risk of neuroblastoma: Assessment of meta-analysis of case-control studies.

Neuroblastoma (NB), a neuroendocrine tumour, is one of the most prevalent cancers in children. The link between LMO1 polymorphisms and NB has been investigated by several groups, rendering inconclusive results. Here, with this comprehensive systematic review and up-to-date meta-analysis, we aim to distinctively elucidate the possible correlation between LMO1 polymorphisms and NB susceptibility. Eligible studies were systematically researched and identified using PubMed, Web of Science and Scopus databases up to 10 February 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the associations. Our findings revealed that rs110419 and rs2168101 polymorphisms were significantly associated with a decreased risk of NB in all genetic models. In addition, the rs4758051 variant appeared protective against NB in homozygous, dominant and allele genetic models, whereas the rs10840002 variant markedly decreased the risk of NB in the allele model. In contrast, the rs204938 polymorphism showed a positive association with NB susceptibility in allele genetic models. In summary, our meta-analysis is the first to provide clear evidence of an association between specific polymorphisms of LMO1 and susceptibility to NB. Of note, additional larger well-designed studies would be helpful to further evaluate and confirm this association.

The 40bp indel polymorphism of MDM2 increase the risk of cancer: An updated meta-analysis.

This meta-analysis aimed to provide an up-to-date comprehensive evaluation on the association between the MDM2 40bp indel polymorphism and cancer susceptibility. Eligible studies were retrieved by searching Web of Science, PubMed, Scopus, and Google scholar databases up to August 27, 2018. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of association between the polymorphism and cancer risk. The findings of this meta-analysis revealed that the 40bp indel polymorphism significantly increased the risk of overall cancer risk in heterozygous (OR=1.06, 95%CI=1.01-1.11, P=0.016) and ID+DD (OR=1.07, 95%CI=1.01-1.14, P=0.027) genotypes. Stratified analysis by cancer type proposed that the study indel variant significantly associated with the risk of gastrointestinal cancer in heterozygous (OR=1.18, 95%CI=1.06-1.32, P=0.003) and ID+DD (OR=1.18, 95%CI=1.06-1.30, P=0.002) genotypes. The present findings showed a significant association between the MDM2 40bp indel polymorphism and overall cancer risk as well as gastrointestinal cancer susceptibility. Larger and well-designed researches are required to validate the findings association in detail.

Association between genetic polymorphisms of long noncoding RNA H19 and cancer risk: a meta-analysis.

Long noncoding RNA (lncRNA) H19, a well-known oncogenic lncRNA, is overexpressed in various cancers. Several studies have investigated the association between polymorphisms in lncRNA H19 and the risk of various cancer types; however, the findings were inconsistent. In this study, we performed a meta-analysis to identify the precise association between H19 polymorphisms and cancer risk. Appropriate studies were retrieved from searching Web of Science, PubMed, Scopus, and Google scholar databases, updated 25 November 2018. The pooled odds ratios (ORs with 95% confidence intervals (CIs) were calculated to estimate the strength of the association between H19 polymorphisms and cancer risk. Our findings revealed that the H19-rs217727 C>T polymorphism is significantly associated with an increased risk of overall cancer in homozygous codominant (OR=1.28, 95% CI=1.04-1.57, P =0.020, TT vs CC), dominant (OR=1.20, 95% CI=1.04-1.37, P =0.010, CT+TT vs CC), recessive (OR=1.21, 95% CI=1.00-1.46, P =0.048, TT vs CT+CC), and allele (OR=1.16, 95% CI=1.05-1.28, P =0.003, T vs C) genetic models. No significant correlations were observed between H19: rs2839698 G>A, rs2107425 C>T, rs2735971 C>T, rs3024270 G>C, rs3741219 T>C, rs2839701 C>G, rs2735469 C>T, rs17658052 G>A, and rs3741216 T>A polymorphisms and overall cancer risk. Stratified analysis by cancer type proposed that the rs217727 variant is associated with increased risk of oral squamous cell carcinoma (OSCC) and lung cancer, whereas the rs2839698 variant is associated with increased risk of gastrointestinal cancer. Taken together, these findings support an association between H19 rs217727, and rs2839698 polymorphisms and cancer susceptibility. Larger and well-designed studies are necessary to further confirm these findings in detail.

Association between PD-1 and PD-L1 Polymorphisms and the Risk of Cancer: A Meta-Analysis of Case-Control Studies.

A number of case-control studies regarding the association of the polymorphisms in the programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) genes with the risk of cancer have yielded inconsistent findings. Therefore, we have conducted a comprehensive, updated meta-analysis study to identify the impact of PD-1 and PD-L1 polymorphisms on overall cancer susceptibility. The findings revealed that PD-1 rs2227981 and rs11568821 polymorphisms significantly decreased the overall cancer risk (Odds Ratio (OR) = 0.82, 95% CI = 0.68-0.99, p = 0.04, TT vs. CT+CC; OR = 0.79, 95% CI = 0.67-0.94, p = 0.006, AG vs. GG, and OR = 0.82, 95% CI = 0.70-0.96, p = 0.020, AG+AA vs. GG, respectively), while PD-1 rs7421861 polymorphism significantly increased the risk of developing cancer (OR = 1.16, 95% CI = 1.02-1.33, p = 0.03, CT vs. TT). The PD-L1 rs4143815 variant significantly decreased the risk of cancer in homozygous (OR = 0.62, 95% CI = 0.41-0.94, p = 0.02), dominant (OR = 0.70, 95% CI = 0.50-0.97, p = 0.03), recessive (OR = 0.76, 95% CI = 0.60-0.96, p = 0.02), and allele (OR = 0.78, 95% CI = 0.63-0.96, p = 0.02) genetic models. No significant association between rs2227982, rs36084323, rs10204525, and rs2890658 polymorphisms and overall cancer risk has been found. In conclusions, the results of this meta-analysis have revealed an association between PD-1 rs2227981, rs11568821, rs7421861, as well as PD-L1 rs4143815 polymorphisms and overall cancer susceptibility.

Investigation of ATG16L1 rs2241880 Polymorphism with Cancer Risk: A Meta-Analysis.

Background and Objectives: Previous studies have investigated the impact of the ATG16L1 rs2241880 (Thr300Ala) polymorphism on individual susceptibility to cancer, but the conclusions are still controversial. To get a more precise evaluation of the correlation between ATG16L1 rs2241880 polymorphism and cancer susceptibility, we performed a meta-analysis of the association of all eligible studies. Materials and Methods: Searches were performed in the Web of Science, PubMed, Scopus and Google Scholar databases up to November 2018. A total of 12 case-control studies from 9 articles comprising 2254 cases and 4974 controls were included. Statistical analysis was achieved by STATA 14.1 and Review Manager 5.3 software. The odds ratios (ORs) with 95% confidence intervals (95% CIs) under five genetic models were used to determine the strength of association among rs2241880 polymorphism and cancer susceptibility. Results: The findings did not support an association between the rs2241880 variant in either the overall study population or the subgroups, based on cancer types and ethnicity in any of the genetic models. As far as we know, our study is the first meta-analysis of the association between rs2241880 polymorphism and cancer risk. Conclusions: In conclusion, the findings of this meta-analysis proposes that the ATG16L1 rs2241880 polymorphism may not play a role in cancer development. Further well-designed studies are necessary to clarify the precise role of the ATG16L1 rs2241880 polymorphism on cancer risk.

Association between P2X7 Polymorphisms and Susceptibility to Tuberculosis: An Updated Meta-Analysis of Case-Control Studies.

Background and Objectives: Several studies inspected the impact of P2X7 polymorphisms on individual susceptibility to tuberculosis (TB), but the findings are still controversial and inconclusive. To achieve a more precise estimation, we conducted a meta-analysis of all eligible studies on the association between P2X7 polymorphisms and TB risk. Materials and Methods: Relevant studies were identified by searching the PubMed, Web of Science, Scopus and Google scholar databases up to November 2018. Twenty-four full-text articles were included in our meta-analysis. The strength of association between P2X7 polymorphisms and TB risk was evaluated by odds ratios (ORs) and 95% confidence intervals (95% CIs) under five genetic models. Results: The findings of this meta-analysis revealed that the rs3751143 variant significantly increased the risk of TB in heterozygous codominant (OR = 1.44, 95%CI = 1.17-1.78, p = 0.0006, AC vs. AA), homozygous codominant (OR = 1.87, 95% CI = 1.40-2.49, p = 0.0004, CC vs. AA), dominant (OR = 1.50, 95% CI = 1.22-1.85, p = 0.0002, AC + CC vs. AA), recessive (OR = 1.61, 95% CI = 1.25-2.07, p = 0.001, CC vs. AC + AA), and allele (OR = 1.41, 95% CI = 1.19-1.67, p < 0.0001, C vs. A) genetic models. Stratified analysis showed that rs3751143 increased the risk of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in all genetic models. Furthermore, the rs3751143 increased risk of TB in the Asian population. The findings did not support an association between the rs2393799, rs1718119, rs208294, rs7958311, and rs2230911 polymorphisms of P2X7 and TB risk. Conclusions: The findings of this meta-analysis suggest that P2X7 rs3751143 polymorphism may play a role in susceptibility to TB in the Asian population. More well-designed studies are required to elucidate the exact role of P2X7 polymorphisms on TB development.

Association Between miR-423 rs6505162 Polymorphism and Susceptibility to Cancer.

BACKGROUND AND AIMS: Previous studies investigated the impact of miR-423 rs6505162 C>A polymorphism on individual susceptibility to risk, but the conclusions are still controversial and inconclusive. We performed a meta-analysis to get a more precise and comprehensive assessment of the association between miR-423 rs6505162 variant and cancer risk. METHODS: Relevant studies were identified by searching the PubMed, Web of Science, Scopus and Google scholar databases up to September 03, 2018. Twenty seven case-control studies comprising 10,500 cases and 13,781 controls were included. The strength of correlation between rs6505162 polymorphism and cancer risk was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs) under six genetic models. RESULTS: The findings showed that rs6505162 variant significantly decreased the risk of cancer in heterozygous codominant (OR = 0.88, 95% CI = 0.79-0.97, p = 0.009, AC vs. CC), dominanat (OR = 0.86, 95% CI = 0.77-0.95, p = 0.005, AC + AA vs. CC), and allele (OR = 0.89, 95% CI = 0.82-0.96, p = 0.003, A vs. C) genetic models. Stratified analyses by cancer types revealed that rs6505162 variant significantly decreased the risk of gastrointestinal cancer, colorectal cancer and lung cancer. The variant was not associated with the risk of esophageal cancer, breast cancer and gastric cancer. In addition this variant was associated with protective effect against cancer in Asian population. CONCLUSION: In conclusion, the findings of this meta-analysis suggests that miR-423 rs6505162 polymorphism may play a role in protection against cancer. More well-designed studies are required to elucidate the exact role of miR-432 polymorphism on cancer development.

Association between the flap endonuclease 1 gene polymorphisms and cancer susceptibility: An updated meta-analysis.

Flap endonuclease 1 (FEN1) has emerged as an important enzyme in the maintenance of genomic instability and preventing carcinogenesis. The relationship between FEN1 -69G>A (rs174538)+4150G>T (rs4246215) polymorphisms and cancer susceptibility has been reported; however, results were inconclusive. In the present study, a meta-analysis of data from eligible reports was carried out to summarize the possible relationship between FEN1 polymorphisms and cancer risk. A total of 11 articles, including 20 studies with 7366 cases and 9028 controls and 18 studies with 6649 cases and 8325 controls for FEN1 rs174538 and FEN1 rs4246215 polymorphisms, respectively, were recruited for meta-analysis. Overall, meta-analyses showed that FEN1 rs174538 and rs4246215 polymorphisms are significantly associated with the decreased risk of cancer. The stratified analysis proposed that both variants were associated with protection against gastrointestinal cancer, breast cancer, hepatocellular cancer, esophageal cancer, gastric cancer, colorectal cancer, and lung cancer. In conclusion, this meta-analysis revealed an association between FEN1 polymorphisms and cancer risk. Additional studies in a larger study population that include subjects from a variety of ethnicities are warranted to further verify our findings.

Survivin rs9904341 polymorphism significantly increased the risk of cancer: evidence from an updated meta-analysis of case-control studies.

AIMS: Survivin, a member of inhibitor of apoptosis protein family, is involved in the regulation of cell cycle and apoptosis. Several studies inspected the association between survivin polymorphisms and the risk of various cancers, but the findings remain controversial. We conducted a meta-analysis intending to certify the association between survivin polymorphisms and cancer risk. METHODS: All analyses were achieved using RevMan 5.3 software and STATA 14.1 software. Eligible studies were collected by comprehensive literature searching Web of Science, PubMed, Scopus, and Google scholar databases. Pooled estimates of odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the overall impact of survivin polymorphisms on cancer risk. RESULTS: The overall analysis indicates that survivin rs9904341 polymorphism significantly increased the risk of cancer in homozygous codominant (OR 1.41, 95% CI 1.19-1.68, p = 0.0001, CC vs GG), dominant (OR 1.22, 95% CI 1.07-1.40, p = 0.003, CG+CC vs GG), recessive (OR 1.34, 95% CI 1.18-1.52, p < 0.0001, CC vs CG+GG), and allele (OR 1.20, 95% CI 1.09-1.31, p = 0.0001, C vs G) inheritance models tested. Stratified based on ethnicity revealed that rs9904341 variant significantly increased the risk of cancer in the Asian population. The findings did not support an association between rs1042489, rs2071214, rs8073069, and rs17878467 polymorphisms and risk of cancer. CONCLUSIONS: The current study suggests that the survivin rs9904341 polymorphism may be associated with the risk of cancer either overall or in the Asian population. However, further larger and well-designed studies are warranted to evaluate this association in detail.

Association of APOBEC3 deletion with cancer risk: A meta-analysis of 26 225 cases and 37 201 controls.

Previous studies have found inconsistent results regarding gene deletion in APOBEC3 (apolipoprotein B mRNA-editing catalytic polypeptide-like 3) and risk of cancer. We conducted a meta-analysis of all eligible case-control studies to find out the associations between APOBEC3 deletion and cancer risk by pooling the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Overall, the findings from 20 studies (13 articles) involving of a total of 26 225 cases and 37 201 controls revealed that DD genotype was associated significantly with increased cancer risk compared to II genotype (OR = 1.25, 95% CI = 1.01-1.56, P = 0.04). Stratified analysis from 10 studies including 14 757 cases and 17 930 controls revealed that I/D variant significantly increased the risk of breast cancer in heterozygous codominant (OR = 1.15, 95% CI = 1.03-1.28, P = 0.02, ID vs II), dominant (OR = 1.15, 95% CI = 1.01-1.31, P = 0.03, ID + DD vs II), overdominant (OR = 1.11, 95% CI = 1.05-1.25, P < 0.0001, ID vs DD + II) and allele (OR = 1.15, 95% CI = 1.13-1.25, P = 0.03, D vs I) inheritance models. In conclusion, the data propose that APOBEC3 deletion is significantly associated with increased susceptibility to cancer in overall and breast cancer. Our findings require well-designed replication in a larger independent genetic association study with larger sample sizes in diverse ethnicities.

Association between miR-34b/c rs4938723 polymorphism and risk of cancer: An updated meta-analysis of 27 case-control studies.

Several studies investigated the association between miR-34b/c rs4938723 polymorphism and the risk of several human cancers, but the findings remain inconclusive. To evaluate the impact of miR-34b/c rs4938723 on cancer risk, we performed a meta-analysis on all available studies including 12 361 cancer cases and 14 270 controls. Eligible studies were identified by searching PubMed, Web of Science, Scopus, and Google scholar databases. Pooled odds ratios with 95% confidence intervals were calculated in codominant, dominant, recessive, overdominant, and allele models to quantitatively estimate the association. The overall findings showed no significant association between miR-34b/c rs4938723 polymorphism and cancer risk in codominant, dominant, recessive, overdominant, and allele inheritance model. However, in stratified analysis by cancer types, the rs4938723 polymorphism significantly increased the risk of gastrointestinal cancer, hepatocellular carcinoma. In addition, the rs4938723 polymorphism was associated with decreased risk of esophageal squamous cell carcinoma, colorectal cancer, and acute lymphoblastic leukemia. The findings did not support an association between rs4938723 variant and digestive tract as well as gastric cancer. In summary, the findings of this meta-analysis indicated that the miR-34b/c rs4938723 polymorphism might be associated with some cancer development. Larger and well-designed studies are necessary to estimate this association in detail.

Lack of Association between miR-605 rs2043556 Polymorphism and Overall Cancer Risk: A Meta-analysis of Case-control Studies.

Growing evidence propose an association between miRNA polymorphisms and cancer susceptibility. This study aimed to examine the impact of miR-605 rs2043556 polymorphism on cancer risk through a meta-analysis based on 3198 cancer cases and 4943 controls. Eligible studies were retrieved by searching Web of Science, PubMed, Scopus, and Google Scholar databases up to August 27, 2018. The pooled Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were calculated using a random-effect model to estimate the strength of association between rs2043556 variant of miR-605 and cancer risk. Overall, no significant association was found between miR-605 rs2043556 polymorphism and cancer risk in heterozygous codominant (OR=0.93, 95% CI=0.76-1.13, p=0.44, AG vs. AA), homozygous codominant (OR=1.01, 95%CI=0.78-1.30, p=0.94, GG vs. AA), dominant (OR=0.95, 95% CI=0.79-1.13, p=0.55, AG+GG vs. AA), recessive (OR=1.07, 95%CI=0.84-1.38, p=0.57, GG vs. AG+AA), overdominant (OR=0.93, 95% CI=0.76-1.12, p=0.43, AG vs. GG+AA), and allele (OR=0.98, 95% CI=0.87-1.10, p=0.73, G vs. A) genetic models tested. Stratified analysis by cancer type revealed that the rs2043556 variant was not associated with digestive tract cancer, breast cancer, gastric cancer as well as lung cancer. Taken together, the findings of this meta-analysis did not support an association between miR-605 rs2043556 polymorphism and cancer susceptibility.

Promoter DNA Methylation and mRNA Expression Level of p16 Gene in Oral Squamous Cell Carcinoma: Correlation with Clinicopathological Characteristics.

The aim of this study was to investigate the relationship between p16 methylation and its expression in oral squamous cell carcinoma (OSCC). Also the contribution of clinicopathological factors, HPV infection and smoking in p16 expression and promoter methylation has been investigated. In this study 67 consecutive OSCC patients and 59 normal individuals were enrolled. All patients were candidates for surgery of oral cavity and fresh tumor biopsies were collected and processed for DNA and RNA extraction. Normal gingival tissues were collected from individuals referred to dentistry clinic and considered as controls. All the cases and controls were checked for HPV infection and then promoter methylation and expression of p16 gene were determined using Methylation-specific PCR (MSP) and real-time PCR (QPCR), respectively. Methylation of p16 in tumors and normal tissues were 59.7 and 38.9%, respectively. Most of hypermethylated samples (>82%) were in high grades. P16 methylation was comparable in HPV+ and HPV- patients or smokers. P16 was overexpressed (~3 fold; p = 0.044) in HPV+ tumors, but it was significantly down-regulated in smoker patients (40% of all tumors). Comparison of P16 expression in OSCC tumors with different degrees of promoter methylation further suggest the relationship of methylation rate and down-regulation of P16 expression. The p16 methylation and expression was differentially affected in patients with HPV infection and the smoker cases. Regardless of the influence of environmental factors, it appears that P16 status is useful for classifying patients with OSCC and for influencing treatment strategies in accordance with this classification. Moreover, targeting the upregulation of p16 could be a promising therapeutic option.

Association between CASP3 polymorphisms and overall cancer risk: A meta-analysis of case-control studies.

Several studies inspected the relationship between caspase-3 (CASP3) polymorphisms and the risk of several human cancers, but the findings remain controversial. We conducted a meta-analysis aiming to inspect the association between CASP3 rs1049216 T>C, rs12108497 C>T, rs4647603 G>A, rs4647602 C>A, rs6948 T>G, rs2705897 A>C, and rs113420705 G>A polymorphisms and cancer risk. Eligible studies were recognized by searching the Web of Science, PubMed, Scopus, and Google Scholar databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to quantitatively evaluate the association between each polymorphism of CASP3 and cancer risk. The rs4647603 variant significantly increased the risk of cancer in an overdominant (OR, 1.44; 95% CI, 1.03-2.01; P = 0.03; AG vs AA+GG) inheritance model. Regarding the rs4647602 variant, the findings revealed that this variant was associated with protection against cancer in homozygous codominant (OR, 0.67; 95% CI, 0.56-0.80; P < 0.00001; AA vs CC), dominant (OR, 0.84; 95% CI, 0.73-0.96; P = 0.009; AC+AA vs CC), recessive (OR, 0.70; 95% CI, 0.61-0.79; P < 0.00001; AA vs AC+CC), and allele (OR, 0.81; 95% CI, 0.75-0.88; P = 0.00001; A vs C) models. The findings suggested that the rs2705897 variant significantly decreased the risk of cancer in heterozygous codominant (OR, 0.80; 95% CI, 0.67-0.94; P = 0.009; AC vs AA), dominant (OR, 0.81; 95% CI, 0.69-0.95; P = 0.009; AC+CC vs AA), overdominant (OR, 0.80; 95% CI, 0.68-0.95; P = 0.01; AC vs CC+AA), and allele (OR, 0.85; 95% CI, 0.74-0.97; P = 0.02; C vs A) models. The results did not support an association between CASP3 rs1049216 and rs6948 polymorphisms and cancer risk. In summary, the findings of this meta-analysis support an association between CASP3 polymorphisms and cancer risk. Larger and well-designed studies are desired to evaluate these associations in detail.