Homozygote Comparison Research Articles

Current Evidence on Associations Between the MMP-7 (-181A>G) Polymorphism and Digestive System Cancer Risk

Matrix metalloproteinases (MMPs) degrade various components of the extracellular matrix and functional polymorphisms in encoding genes may contribute to genetic susceptibility to many cancers. Up to now, associations between MMP-7 (-181A>G) and digestive system cancer risk have remained inconclusive. To better understand the role of the MMP-7 (-181A>G) genotype in digestive cancer development, we conducted this comprehensive meta-analysis encompassing 3,518 cases and 4,596 controls. Overall, the MMP-7 (-181A>G) polymorphism was associated with higher digestive system cancer risk on homozygote comparison (GG vs. AA, OR=1.21, 95% CI = 1.12-1.60) and in a dominant model (GG/GA vs. AA, OR=1.16, 95% CI =1.03-1.46). On subgroup analysis, this polymorphism was significantly linked to higher risks for gastric cancer (GG vs. AA, OR=1.22, 95% CI = 1.02- 1.46; GA vs. AA, OR=1.82, 95% CI =1.16-2.87; GG/GA vs. AA, OR=1.13, 95% CI =1.01-1.27; GG vs. GA/AA, OR= 1.25, 95% CI = 1.06-2.39. We also observed increased susceptibility to colorectal cancer and esophageal SCC in both homozygote (OR = 1.13, 95% CI = 1.06-1.26) and heterozygote comparisons (OR = 1.45, 95% CI = 1.11-1.91). In the stratified analysis by controls, significant effects were only observed in population-based studies (GA vs. AA, OR=1.16, 95% CI=1.08-1.50; GA/AA vs. GG, OR=1.10, 95% CI=1.01-1.72). According to the source of ethnicity, a significantly increased risk was found among Asian populations in the homozygote model (GG vs. AA, OR=1.40, 95% CI=1.12-1.69), heterozygote model (GA vs. AA, OR=1.26, 95% CI=1.02-1.51), and dominant model (GG/GA vs. AA, OR=1.18, 95% CI=1.08-1.55). Our findings suggest that the MMP-7 (-181A>G) polymorphism may be a risk factor for digestive system cancer, especially among Asian populations.

Polymorphisms of microRNA Sequences or Binding Sites and Lung Cancer: A Meta-Analysis and Systematic Review

ObjectiveFunctional single nucleotide polymorphisms (SNPs) of microRNA (miRNA) sequences or binding sites (miRNA-SNPs) are associated with lung cancer risk and survival. The objective of this study was to systematically review genetic association studies about miRNA-SNPs in lung cancer.MethodsEligible genetic association studies were retrieved from databases of PubMed, EMBASE, China National Knowledge Infrastructure and SinoMed. Two investigators selected related studies and assessed methodological quality independently. Quantitative data synthesis was conducted for common SNPs of miRNA (miRNA-196a2 rs11614913, miRNA146a rs2910164, miRNA149 rs2292832, miRNA-605 rs2043556 and miRNA499 rs3746444). GRADE profiler was used to grade the quality of evidence for each miRNA-SNP.Results15 eligible studies and 27 miRNA-SNPs were retrieved and 10 miRNA-SNPs were reported with a significant association with susceptibility to or survival of lung cancer. Methodological quality of eligible studies was adequate with an average score of 8.5. miRNA-196a2 rs11614913 polymorphism was associated with increased lung cancer risk (homozygote comparison, OR = 1.299, 95% CI: 1.096–1.540; dominant model, OR = 1.217, 95% CI: 1.041–1.421) and decreased survival. And according to GRADE profiler, quality of evidence was moderate for MYCL1 rs3134615, while quality of the other significant associations was low.ConclusionsBased on this first systematic review about miRNA-SNPs in lung cancer, quality of evidence was low for most genetic association studies. Polymorphisms of miRNA-196a2 rs11614913 and MYCL1 rs3134615 could be potential biomarkers of lung cancer.

Lack of association between XRCC3 rs861539 (C > T) polymorphism and lung cancer risks: an update meta-analysis

X-ray repair cross-complementing protein 3 (XRCC3) belongs to DNA double-strand break repair pathway and XRCC3 rs861539 (C > T) polymorphism has been suspected with lung cancer risk. However, results from previous studies are inconclusive and affected by bias. Electronic databases of PubMed, EMBASE, China National Knowledge Infrastructure, and SinoMed were searched. References of relative reviews were also screened. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to estimate the association strength. A number of 18 eligible studies with 6 studies of Asians, 11 of Caucasians, and 1 of African were extracted and analyzed, including 4,896 lung cancer cases and 6,360 controls. No significant correlation between XRCC3 polymorphism and lung cancer risk was observed in homozygote comparison (CC vs. TT; OR=0.877; 95 % CI, 0.659, 1.168), heterozygote comparison (CT vs. TT; OR=0.857; 95 % CI, 0.675, 1.089), dominant model (CC/CT vs. TT; OR=0.862; 95 % CI, 0.663, 1.123), or recessive model (CC vs. CT/TT; OR=1.047; 95 % CI, 0.956, 1.145). Subgroup analyses of ethnicity and controls did not reveal any significant association with lung cancer risk. No publication bias was detected. In this update meta-analysis of 18 studies and 11,256 participants, we find that XRCC3 rs861539 polymorphism does not contribute to lung cancer risk and there is no difference between Asians and Caucasians.

An updated meta-analysis of the Fc receptor-like 3 –169T/C polymorphism and rheumatoid arthritis risk

Objectives: Published studies have shown conflicting results concerning the association between the –169T/C promoter polymorphism in the Fc receptor-like 3 (FCRL3) gene and rheumatoid arthritis (RA). In this study we conducted an up-to-date meta-analysis to examine the relationship.Method: We searched the PubMed database for all papers published up to 20 April 2012. Overall, 18 case–control studies with 12 620 cases and 12 613 controls were retrieved based on the search criteria for RA susceptibility related to the FCRL3 –169T/C polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed using the Egger test.Results: We found that the FCRL3 –169T/C polymorphism increased the risk for RA overall in genetic models (allelic contrast: OR 1.09, 95% CI 1.03–1.14, p = 0.001; homozygote comparison: OR 1.20, 95% CI 1.08–1.34, p = 0.001; dominant genetic model: OR 1.03, 95% CI 1.01–1.05, p = 0.001). Stratified analysis by race also showed a significant positive association with Asians and Caucasians. Subgroup analysis of rheumatoid factor (RF) revealed a slightly positive relationship between the FCRL3 –169T/C polymorphism and RF-positive RA risk. No obvious evidence of publication bias was detected in the overall analysis.Conclusion: Our study indicates that the FCRL3 –169T/C polymorphism is significantly associated with increased RA risk.

Association of SMAD7 rs12953717 polymorphism with cancer: a meta-analysis.

BackgroundAccumulating evidence has suggested that Mothers against decapentaplegic homolog 7 (SMAD7) rs12953717 polymorphism might be related to cancer risk. However, epidemiologic findings have been inconsistent. We therefore performed a meta-analysis to clarify the association between the SMAD7 rs12953717 polymorphism and cancer risk.MethodsA comprehensive search was conducted to identify all eligible studies of SMAD7 rs12953717 polymorphism and cancer risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) to give a sense of the precision of the estimate. Heterogeneity, publication bias, and sensitivity analysis were also explored.ResultsA total of 14 case-control studies, including 16928 cases and 14781 controls, were included in the present meta-analysis. The overall results showed that the variant genotypes were associated with a significantly increased risk of all cancer types (homozygote comparison, OR = 1.23, 95%CI = 1.10–1.38, P<0.01; heterozygote comparison, OR = 1.12, 95%CI = 1.02–1.22, P = 0.02; recessive model, OR = 1.17, 95%CI = 1.07–1.29, P<0.01; dominant model, OR = 1.15, 95%CI = 1.06–1.25, P<0.01; allelic model, OR = 1.12, 95%CI = 1.06–1.18, P<0.01). Further sensitivity analysis confirmed the significant association. In the subgroup analysis by ethnicity, SMAD7 rs12953717 polymorphism was significantly associated with cancer risk in both Caucasians and Asians. In the subgroup analysis by cancer types, SMAD7 rs12953717 polymorphism was significantly associated with colorectal cancer.ConclusionsOur investigations demonstrate that rs12953717 polymorphism is associated with the susceptibility of cancer. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.

The Interleukin-10 Promoter Polymorphism rs1800872 (-592C&gt;A), Contributes to Cancer Susceptibility: Meta-Analysis of 16 785 Cases and 19 713 Controls

Interleukin-10 (IL-10) is a multifunctional cytokine which participates in the development and progression of various malignant tumors. To date, a number of case–control studies were conducted to detect the association between IL-10-592C>A polymorphism and cancer risk in humans. However, the results of these studies on the association remain conflicting. In an effort to solve this controversy, we performed a meta-analysis based on 70 case–control studies from 65 articles, including 16 785 cancer cases and 19 713 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The overall results suggested that the variant homozygote genotype AA of the IL-10-592C>A polymorphism was associated with a moderately decreased risk of all cancer types (OR = 0.90, 95% CI = 0.83–0.98 for homozygote comparison, OR = 0.92, 95% CI = 0.86–0.98 for recessive model). In the stratified analyses, the risk remained for studies of smoking-related cancer, Asian populations and hospital-based studies. These results suggested that the IL-10-592C>A polymorphism might contribute to the cancer susceptibility, especially in smoking-related cancer, Asians and hospital-based studies. Further studies are needed to confirm the relationship.

Meta-Analysis of Microsomal Epoxide Hydrolase Gene Polymorphism and Risk of Hepatocellular Carcinoma

BackgroundHepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in microsomal epoxide hydrolase (mEH). Previous work suggests an association between the Tyr113His and His139Arg mEH polymorphisms and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent.MethodsPubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His and His139Arg mEH polymorphism and susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsEleven studies were included in the meta-analysis, involving 1,696 HCC cases and 3,600 controls. The 113His- mEH allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.35, 95% CI = 1.04–1.75, p = 0.02), homozygote comparison (OR = 1.65, 95% CI = 1.07–2.54, p = 0.02) and a recessive genetic model (OR = 1.54, 95% CI = 1.21–1.96, p<0.001), while individuals carrying the Arg139Arg mEH genotype had no association with increased or decreased risk of HCC.ConclusionThe 113His- allele polymorphism in mEH may be a risk factor for hepatocarcinogenesis, while the mEH 139Arg- allele may not be a risk or protective factor. There is substantial evidence that mEH polymorphisms interact synergistically with other genes and the environment to modulate risk of HCC. Further large and well-designed studies are needed to confirm these conclusions.

The TERT MNS16A polymorphism contributes to cancer susceptibility: Meta-analysis of the current studies

The MNS16A polymorphism in the telomerase reverse transcriptase (TERT) gene has been implicated in cancer risk in multiple populations and various types of cancers; however, the results of previous studies exploring this association were inconclusive. To more precisely evaluate the relationship between the TERT MNS16A polymorphism and cancer risk, we performed a meta-analysis based on 8 studies described in 7 articles comprising 7864 controls and 4355 cases. The summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to assess the strength of the association in a fixed-effects model or a random-effects model where appropriate. Heterogeneity among articles and their publication bias were also tested. Overall, the pooled results indicated that the MNS16A polymorphism was significantly associated with increased cancer risk in the homozygote comparison model (SS vs. LL: OR=1.280, 95% CI 1.060–1.547) and the recessive model (SS vs. LL+SL: OR=1.201, 95% CI 1.004–1.436). In the stratified analyses, a statistically significant association was observed among Caucasians and in population-based studies. We also performed the analyses by cancer type, and a significantly increased risk of glioma was found in four genetic models. Our results suggest that the TERT MNS16A polymorphism most likely contributes to an increased risk of cancer. Moreover, the same relationship was found when the studies were stratified by cancer type, ethnicity and source of controls.

The Glutathione S-Transferase P1 341C&gt;T Polymorphism and Cancer Risk: A Meta-Analysis of 28 Case-Control Studies

BackgroundGSTP1, which is one major group of the glutathione S-transferase family, plays an important role in the metabolism of carcinogens and toxins, reducing damage of DNA as a suppressor of carcinogenesis. The 341C>T polymorphism of the GSTP1 has been implicated in cancer risk through cutting down its metabolic detoxification activities. However, results from previous studies remain conflicting rather than conclusive. To clarify the correlation and provide more statistical evidence for detecting the significance of 341C>T, a meta-analysis was conducted.Methodology/Principal FindingsThe relevant studies were identified through searching of PubMed, Embase, ISI Web of Knowledge and China National Knowledge Infrastructure in August 2012, and selected based on the established inclusion criteria for publications, then a meta-analysis was performed to quantitatively summarize the association of GSTP1 341C>T polymorphism with cancer susceptibility. Stratified analyses were employed to identify the source of heterogeneity. Publication bias was evaluated as well as sensitivity analysis. Based on 28 case-control studies with 13249 cases and 16798 controls, the pooled results indicated that the variant genotypes significantly increased the risk of cancer in homozygote comparison (TT versus CC: P = 0.012, OR = 1.40, 95% CI: 1.08–1.81, P het. = 0.575), and recessive model (TT versus CT/CC: P = 0.012, OR = 1.40, 95% CI: 1.08–1.81, P het. = 0.562). This was confirmed when stratified analyses were conducted according to ethnicity, source of control, matched control, quality score and cancer types. Moreover, significantly increased risk of cancer was also found in lung cancer (heterozygote comparison and dominant model). The stability of these observations was confirmed by a sensitivity analysis. Begger's funnel plot and Egger's test did not reveal any publication bias.Conclusions/SignificanceThis meta-analysis suggests that the GSTP1 341C>T polymorphism may contribute to genetic susceptibility to cancer, especially to lung cancer, and in Asian population. Nevertheless, additional well-designed studies focusing on different ethnicity and cancer types are needed to provide a more exact and comprehensive conclusion.

Lack of association between MHTFR Glu429Ala polymorphism and breast cancer susceptibility: a systematic review and meta-analysis of 29 research studies

The association between MHTFR Glu429Val polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 29 studies including 8,649 cases and 18,672 controls were involved in this meta-analysis. Overall, no significant associations were found between MTHFR Glu429Ala polymorphism and breast cancer risk when all studies were pooled into the meta-analysis (Glu/Glu vs Ala/Ala: OR = 0.891, 95 % CI = 0.782-1.015; Glu/Ala vs Ala/Ala: OR = 0.874, 95 % CI = 0.760-1.006; dominant model: OR = 0.885, 95 % CI = 0.775-1.012; and recessive model: OR = 0.989, 95 % CI = 0.931-1.051). In the subgroup analysis by ethnicity, significantly elevated breast cancer risk was associated with Glu/Glu variant genotype in homozygote comparison and recessive genetic model (Glu/Glu vs Ala/Ala: OR = 0.78, 95 % CI = 0.63-0.97; Glu/Glu vs Glu/Ala: OR = 0.92, 95 % CI = 0.85-0.99; recessive model: OR = 0.91, 95 % CI = 0.85-0.97), while no significant associations were found for all comparison models in other ethnicity populations. In conclusion, this meta-analysis suggests that the MTHFR Glu429Ala polymorphism may be not associated with breast cancer development.

Association between the ghrelin Leu72Met polymorphism and type 2 diabetes risk: A meta-analysis

AimsData on the association between the ghrelin Leu72Met polymorphism and type 2 diabetes are conflicting. A meta-analysis was performed on this topic. MethodsWe searched for case–control studies using electronic databases (Medline and PubMed) and reference lists of studies. Odds ratios (OR) and 95% confidence intervals (CI) assuming dominant, recessive and homozygote comparison genetic models were calculated. ResultsSix case–control studies involving a total of 3417 cases and 3081 controls were included in this meta-analysis. No association was found between the ghrelin Leu72Met polymorphism and type 2 diabetes risk in the overall population in dominant, recessive and homozygote comparison models. However, in subgroup analyses stratified by ethnicity, we found that the risk for type 2 diabetes was decreased in subjects with Met72+ genotypes in Caucasians (OR=0.79, 95% CI: 0.64–0.98, Pz=0.030). ConclusionThe ghrelin Leu72Met polymorphism was protective against type 2 diabetes in Caucasians. Future studies performed in larger sample size are needed to allow a more definitive conclusion.

Current Evidence on the Association between Mmp-7 (-181a&gt;G) Polymorphism and Digestive System Cancer Risk

The matrix metalloproteinase (MMPs) can degrade various components of the extracellular matrix and its functional genetic polymorphisms may contribute to genetic susceptibility to many cancers. Up to now, the association between MMP-7 (-181A>G) and digestive system cancer risk remain inconclusive. To better understand the role of MMP-7 (-181A>G) genotype in digestive cancer development, we conducted this comprehensive meta-analysis encompassing 3,518 cases and 4,596 controls. Overall, the MMP-7 (-181A>G) polymorphism was associated with higher digestive system cancer risk in homozygote comparison (GG vs. AA, OR=1.21, 95% CI=1.12-1.60) and dominant model (GG/GA vs. AA, OR=1.16, 95% CI=1.03-1.46). In subgroup analysis, this polymorphism was significantly linked to higher risks for gastric cancer (GG vs. AA, OR=1.22, 95% CI=1.02-1.46; GA vs. AA, OR=1.82, 95% CI=1.16-2.87; GG/GA vs. AA, OR=1.13, 95% CI=1.01-1.27; GG vs. GA/AA, OR=1.25, 95% CI=1.06-2.39. We also observed increased susceptibility of colorectal cancer and ESCC in homozygote comparison (OR=1.13, 95% CI=1.06-1.26) and heterozygote comparison (OR=1.45, 95% CI=1.11-1.91) respectively. In the stratified analysis by controls, significant effects were only observed in population-based studies (GA vs. AA, OR=1.16, 95% CI=1.08- 1.50; GA/AA vs. GG, OR=1.10, 95% CI=1.01-1.72). According to the source of ethnicity, a significantly increased risk was found among Asian populations in homozygote model (GG vs. AA, OR=1.40, 95% CI=1.12-1.69), heterozygote model (GA vs. AA, OR=1.26, 95% CI=1.02-1.51), and dominant model (GG/GA vs. AA, OR=1.18, 95% CI=1.08-1.55). Our findings suggest that the MMP-7 (-181A>G) polymorphism may be a risk factor for digestive system cancer, especially among Asian population.

Current Evidence on the Association between Cytotoxic T-Lymphocyte Antigen 4 +49G &gt; A Polymorphism and Digestive System Cancer Risks: a Meta-analysis Involving 11,923 Subjects

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) plays an important role in downregulating T cell activation and proliferation. The CTLA-4 +49G > A polymorphism is one of the most commonly studied polymorphisms in this gene due to its association with many cancer types, but the association between CTLA-4 +49G > A polymorphism and digestive system cancer risks remain inconclusive. An updated meta-analysis based on 17 independent case-control studies consisting of 5,176 cancer patients and 6,747 controls was performed to address this association. Overall, there was no statistically increased risk of digestive system cancers in every genetic comparison.In subgroup analysis, this polymorphism was significantly linked to higherrisks for pancreatic cancer (GG vs. AA, OR=1.976, 95% CI = 1.496-2.611; GA vs. AA, OR=1.433, 95% CI = 1.093-1.879; GG/GA vs. AA, OR=1.668, 95% CI = 1.286-2.164; GG vs. GA/AA, OR = 1.502, 95% CI = 1.098-2.054; G vs. A, OR=1.394, 95%CI = 1.098-1.770). We also observed increased susceptibility of hepatocellular cell carcinoma in homozygote comparison (OR=1.433, 95% CI = 1.100-1.866) and dominant model (OR=1.360, 95% CI = 1.059-1.746). According to the source of controls, significant effects were only observed in hospital-based studies (GA/AA vs. GG, OR=1.257, 95% CI = 1.129-1.399). In the stratified analysis by ethnicity, No significantly increased risks were found in either Asian or Caucasian. Our findings suggest that the CTLA-4 +49G > A polymorphism may be not associated with an elevated digestive system cancer risks.

MEH Tyr113His polymorphism and the risk of ovarian cancer development

BackgroundThe causes of ovarian cancer are complex and may be influenced by many factors, including polymorphism in the microsomal epoxide hydrolase (mEH) gene. Previous work suggests an association between the Tyr113His mEH polymorphism rs1051740 and susceptibility to ovarian cancer, but the results have been inconsistent.MethodsPubMed, EMBASE, Google Scholar, and Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His mEH polymorphism and susceptibility to ovarian cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsFive studies involving 2,566 cases and 2,839 controls were included. Although the polymorphism did not affect ovarian cancer risk in the allelic contrast model (OR = 0.99, 95% CI = 0.83-1.17, P = 0.86), the mutant CC genotype was significantly associated with increased risk in the homozygote comparison (OR = 1.20, 95% CI = 1.01-1.43, P = 0.04) and recessive genetic models (OR = 1.20, 95% CI = 1.01-1.41, P = 0.03). The wild-type TT genotype was not associated with higher or lower ovarian cancer risk in the dominant genetic model (OR = 1.04, 95% CI = 0.83-1.29, P = 0.74). These results were robust to sensitivity analysis.ConclusionsThe CC genotype of Tyr113His mEH may confer increased risk of ovarian cancer. These conclusions should be verified in large and well-designed studies.

The Pro12Ala Polymorphism in the Peroxisome Proliferator-Activated Receptor Gamma-2 Gene (PPARγ2) Is Associated with Increased Risk of Coronary Artery Disease: A Meta-Analysis

BackgroundContradictory results have been reported regarding the association between Pro12Ala polymorphism of PPARγ2 and coronary artery disease (CAD). We sought to estimate the inconsistent results by performing a comprehensive meta-analysis.MethodsStudies in English or Chinese publications were identified by screening MEDLINE, Embase, CNKI, Wanfang and CBM. 22 studies including 8948 cases and 14427 controls were selected. A random-effects model was applied to combine the divergent outcomes of the individual studies, while addressing between-study heterogeneity and publication bias.ResultsThe Pro12Ala polymorphism of control population followed Hardy-Weinberg equilibrium for all studies (P>0.05). Overall, a marginal increased risk of CAD under the recessive genetic model (AlaAla vs ProAla+ProPro: P = 0.04, OR = 1.31, 95%CI 1.01–1.69, Pheterogeneity = 0.67, I2 = 0%) and the homozygote comparison (AlaAla vs ProPro: P = 0.04,OR = 1.30, 95%CI 1.01–1.68, Pheterogeneity = 0.68, I2 = 0%) was observed. In the subgroup analysis by ethnicity, carriers of AlaAla homozygotes had a significant increased risk for CAD among Caucasians (AlaAla vs ProAla+ProPro: P = 0.01, OR = 1.45, 95%CI 1.08–1.96, Pheterogeneity = 0.48, I2 = 0%; AlaAla vs ProPro: P = 0.02,OR = 1.44, 95%CI 1.07–1.93, Pheterogeneity = 0.46, I2 = 0%). After dividing into population source, the CAD risk magnitude of hospital-based studies was distinctly strengthened under the recessive model (P = 0.03,OR = 1.85,95%CI 1.07–3.19, Pheterogeneity = 0.87,I2 = 0%) and the homozygote comparison (P = 0.03,OR = 1.83, 95%CI 1.06–3.16, Pheterogeneity = 0.88, I2 = 0%). There was no observable publication bias as reflected by funnel plot and Egger’s linear regression test (t = -0.12, P = 0.91).Conclusion:Our results demonstrated that the PPARγ2 Pro12Ala polymorphism might be risk-conferring locus for the progression of CAD among Caucasians, but not among Asians.

Associations Between Three Polymorphisms in the Interleukin-4 Receptor Gene and Risk of Cancer: a Meta-analysis

Interleukin-4 receptor (IL-4R) gene single nucleotide polymorphisms (SNPs) are implicated in cancer development. However, results from the published reports have remained inconclusive. The objective of this study was to conduct a meta-analysis investigating the association between polymorphisms in IL-4R gene and cancer risk. Pubmed, EMBASE and China National Knowledge Infrastructure (CNKI) were searched for case- control studies published up to October 30, 2012 that investigated IL-4R polymorphisms and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of any associations. Three IL-4R polymorphisms (Q576R, rs1801275; I75V, rs1805010; S503P, rs1805015) in 21 case-control studies were analyzed. Our meta-analysis indicated that these three polymorphisms are not associated with cancer risk when all studies were pooled together. In the subgroup analysis by tumor site, the results showed that Q576R G allele carriers were associated with a significantly decreased cervical cancer risk (recessive model: OR = 0.77, 95%CI = 0.60-0.98; homozygote comparison: OR = 0.76, 95%CI = 0.58-0.98). I75V G allele carriers were associated with a decreased risk of renal cancer (dominant model = 0.71, 95%CI = 0.57-0.89, heterozygote comparison: OR = 0.69, 95%CI = 0.55-0.87). When stratified by ethnicity, Q576R G allele carriers were associated with a decreased cancer risk in Caucasians (dominant model: OR = 0.90, 95%CI = 0.83-0.98; heterozygote comparison: OR = 0.89, 95%CI = 0.82-0.98). I75V G allele carriers were associated with a decreased cancer risk in Asians (heterozygote comparison: OR = 0.76, 95%CI = 0.62-0.94). S503P C allele carriers were also associated with a decreased cancer risk in Asians (CC VS TT: OR = 0.29, 95%CI = 0.08-0.99). Our results suggest that Q576R, I75V and S503P may be associated with a decreased cancer risk for certain types of cancers and in some specific ethnic groups. Future case-control studies with large sample size are needed to evaluate these associations in detail.

An association between XPC Lys939Gln polymorphism and the risk of bladder cancer: a meta-analysis

The polymorphism Lys939Gln in xeroderma pigmentosum complementation group C (XPC) gene has been reported to be associated with bladder cancer in some studies, though the results remain inconclusive. To explore this relationship between XPC Lys939Gln polymorphism and the susceptibility for bladder cancer and the impact of smoking exposures, a cumulative meta-analysis was performed in this study. PubMed and EMBASE databases have been systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between XPC Lys939Gln polymorphism and susceptibility to bladder cancer (BC). Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated. Thirteen studies were chosen in this meta-analysis, involving 4,927 BC cases (1,119 Asian, 2,670 Caucasian, and 1,138 mixed) and 5,185 controls (1,399 Asian, 2,629 Caucasian, and 1,157 mixed). The XPC 939Gln allele was significantly associated with increased risk of BC based on allelic contrast (OR = 1.11, 95 % CI = 1.02-1.21), homozygote comparison (OR = 1.35, 95 % CI = 1.08-1.68), and a recessive genetic model (OR = 1.36, 95 % CI = 1.09-1.68). The results from the present meta-analysis indicated that the 939Gln polymorphism in XPC is a risk factor for bladder carcinogenesis. Further large and well-designed studies are needed to confirm this conclusion.

Association of MDR1 Gene Polymorphisms with Susceptibility to Hepatocellular Carcinoma in the Chinese Population

The objective of this study was to evaluate the association of MDR1 gene polymorphisms with susceptibility to hepatocellular carcinoma (HCC). A total of 689 HCC patients and 680 cancer-free subjects were enrolled. Human MDR1 gene polymorphisms were investigated by created restriction site- polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Multiple logistic regression models were applied to estimate the association between MDR1 gene polymorphisms and susceptibility to HCC. We detected a novel c.4125A>C polymorphism and our findings suggested that this variant was significantly associated with susceptibility to HCC. A significantly increased susceptibility to HCC was noted in the homozygote comparison (CC versus AA: OR=1.621, 95% CI 1.143-2.300, χ2=7.4095, P=0.0065), recessive model (CC versus AC+AA: OR=1.625, 95% CI 1.167-2.264, χ2=8.3544, P=0.0039) and allele contrast (C versus A: OR=1.185, 95% CI 1.011-1.389, χ2=4.4046, P=0.0358). However, no significant increase was observed in the heterozygote comparison (AC versus AA: OR=0.995, 95% CI 0.794-1.248, χ2=0.0017, P=0.9672) and dominant model (CC+AC versus AA: OR=1.106, 95% CI 0.894-1.369, χ2=0.8560, P=0.3549). These findings suggest that the c.4125A>C polymorphism of the MDR1 gene might contribute to susceptibility to HCC in the Chinese population. Further work will be necessary to clarify the relationship between the c.4125A>C polymorphism and susceptibility to HCC on larger populations of diverse ethnicity.

Quantitative assessment of the association between miR-196a2 rs11614913 polymorphism and gastrointestinal cancer risk

Published data on the association between miR-196a2 rs11614913 polymorphism and risk of gastrointestinal (GI) cancers are inconsistent among studies. To clarify the association, we performed a comprehensive literature search and a meta-analysis. We searched multiple databases to identify genetic association studies investigating the effect of miR-196a2 rs11614913 polymorphism on GI cancers with the last report up to January 18, 2012. The odds ratio (OR) and its 95 % confidence interval (95 % CI) were calculated to assess the strength of association. A total of 13 studies including 4,947 cases and 5,642 controls based on the search criteria were involved in this meta-analysis. In the overall analysis, it was suggested that variant C allele of miR-196a2 rs11614913 polymorphism could significantly increase risk of GI cancers in different genetic models (C vs T: OR = 1.17, 95 % CI = 1.07-1.28, P = 0.0008; CT + CC vs TT: OR = 1.26, 95 % CI = 1.08-1.48, P = 0.004; CC vs CT + TT: OR = 1.23, 95 % CI = 1.08-1.39, P = 0.002; CC vs TT: OR = 1.55, 95 % CI = 1.24-1.94, P = 0.0001; CT vs TT: OR = 1.20, 95 % CI = 1.02-1.40, P = 0.03). When stratified by ethnicity, we found a significant association in Asian population, as well as Caucasian population. When stratified by cancer types, we found a significant association in colorectal cancer, as well as esophageal cancer. We did not find a significant association between miR-196a2 rs11614913 polymorphism and hepatocellular carcinoma risk. For gastric cancer, a significantly increased cancer risk was observed only in homozygote comparison. This meta-analysis demonstrates that miR-196a2 rs11614913 polymorphism is significantly associated with risk of GI cancers.

Cyclin D1 polymorphism and oral cancer: a meta-analysis

Cyclin D1 (CCND1) plays a critical role in the G1 to S-phase cell cycle transition. Data on the association between the CCND1 A870G polymorphism and oral cancer are conflicting. To assess the relationship between the CCND1 A870G genotype and the risk of developing oral cancer, we performed a meta-analysis. We searched PubMed to December 1, 2011, for studies on this topic that had been published in the English. For each study, we calculated odds ratios (ORs) and 95 % confidence intervals (CIs), assuming the frequency of allele comparison, homozygote comparison, recessive and dominant genetic models. We then calculated pooled ORs and 95 % CIs. Seven studies were included in the meta-analysis. The CCND1 G allele was not associated with oral cancer in the frequency of allele comparison (G vs. A: OR = 0.882; 95 % CI = 0.684-1.137; p = 0.001 for heterogeneity). In the subgroup analysis, the CCND1 G allele was associated with a borderline significantly decreased risk of developing oral cancer in Asians in the frequency of allele comparison (G vs. A: OR = 0.800; 95 % CI = 0.636-1.006; p = 0.089 for heterogeneity), and the association between the GG genotype and oral cancer was significant in Asians with respect to both the homozygote comparison (GG vs. AA: OR = 0.644; 95 % CI = 0.491-0.843; p = 0.186 for heterogeneity) and the dominant genetic model (GG + AG vs. AA: OR = 0.713; 95 % CI = 0.584-0.870; p = 0.293 for heterogeneity). Our analysis provides evidence that genotypes for the CCND1 A870G polymorphism may be associated with an increased risk of developing oral cancer in the Asian population.