Leptin rs2167270 G > A (G19A) polymorphism may decrease the risk of cancer: A case-control study and meta-analysis involving 19 989 subjects

Accumulating evidence has suggested that leptin (LEP) is very important for the development of cancer. Recently, a number of case-control studies about the relationship of the rs2167270 G > A (G19A) variants in the LEP gene with the risk of cancer have yielded inconsistent results. In this study, we have carried out a case-control study [1063 esophagogastric junction adenocarcinoma (EGJA) cases and 1677 controls] in a Chinese population. Furthermore, we carried out a pooled-analysis of 13 studies involving 8059 cancer patients and 11 930 controls to assess whether the LEP G19A locus was associated with overall cancer susceptibility. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were harnessed to evaluate the potential association. In our case-control study, we found an association between the carriers of LEP 19A allele and EGJA risk. In addition, the results of meta-analysis also suggested significant associations with cancer risk (A vs G: OR = 0.92, 95% CI = 0.88–0.97, P = 0.001; AA vs GG: OR = 0.83, 95% CI = 0.74–0.93, P = 0.001, GA/AA vs GG: OR = 0.93, 95% CI = 0.88–0.99, P = 0.023 and AA vs GG/GA: OR = 0.83, 95% CI = 0.74–0.92, P < 0.001). Upon conducting a stratified analysis, we found that LEP 19A allele might decrease the susceptibility of non-Hodgkin lymphoma (NHL) and colorectal cancer (CRC). In a stratified-by-ethnicity analysis, significant associations were also found in Asians, Caucasians, and mixed populations. We can conclude that the LEP G19A polymorphism constitutes a decreased risk of cancer.     

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.     

Quantitative assessment of the association between TAP2 rs241447 polymorphism and cancer risk

The findings regarding the relation of transporter associated with antigen processing (TAP) to cancer risk have been inconsistent. The aim of this study was to comprehensively evaluate the association between TAP2 rs241447 polymorphism and cancer susceptibility. A meta-analysis of nine investigations with 2800 cases and 1620 controls was conducted to gain a better understanding of the effect of TAP2 rs241447 polymorphism on cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the correlation between TAP2 gene polymorphism and cancer susceptibility. The pooled results from TAP2 rs241447 polymorphism showed a decreased risk of cancer in two dominant genetic models (GG + AG vs AA: OR = 0.86, 95% CI, 0.75-0.99; AG vs AA: OR = 0.85, 95% CI, 0.73-0.99). From the subgroup analysis, decreased cancer susceptibility was found in Caucasians (GG + AG vs AA: OR = 0.82, 95% CI, 0.68-0.99), especially among the subgroup of cervical carcinoma (GG + AG vs AA: OR = 0.82, 95% CI, 0.69-0.96; AG vs AA: OR = 0.83, 95% CI, 0.70-0.99). Overall, the results suggest that TAP2 rs241447 polymorphism contributes to decreased cancer susceptibility.     

Associations of Genetic Variants in the PSCA,MUC1 and PLCE1 Genes with Stomach Cancer Susceptibility in a Chinese Population

BackgroundSeveral genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs).MethodsTo evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP) analysis was also performed to validate all statistically significant findings.ResultsIn the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07–1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03–1.63), PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02–1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00–1.59), or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15–1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14–1.84), respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60–0.98). Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03–1.64), when compared with those having 0–1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer.ConclusionsThis study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different ethnicities are warranted to validate our findings.     

A genetic variant in LINGO2 contributes to the risk of gestational diabetes mellitus in a Chinese population

Genome-wide association studies (GWASs) showed that three single nucleotide polymorphisms (SNPs; rs10968576, rs1412239, and rs824248) in the leucine-rich repeat and Ig domain containing 2 (LINGO2) were associated with obesity or type 2 diabetes (T2D). We aimed to determine the influence of the LINGO2 variants on the gestational diabetes mellitus (GDM) risk. Thus, we performed a case–control study including 964 GDM cases and 1,021 controls to test the associations between the three LINGO2 variants (rs10968576, rs1412239, and rs824248) and susceptibility to GDM. Logistic regression analyses showed no significant association between LINGO2 variations (rs10968576 and rs1412239) and GDM susceptibility, but we observed that LINGO2 rs824248 A > T was significantly associated with an increased risk of GDM using the dominant model (TT/AT vs. AA: adjusted odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.05–1.51; p = 0.012) and the additive model (TT vs. AT vs. AA: adjusted OR = 1.16, 95% CI = 1.03–1.31; p = 0.016). In the additive model, a stronger risk effect of rs824248 was observed among obese women (prepregnancy body mass index [BMI] > 22 kg/m², adjusted OR = 1.34, 95% CI = 1.12–1.59) compared with that in lean women (prepregnancy BMI ≤ 22 kg/m², adjusted OR = 1.0², 95% CI = 0.86–1.21; p = 0.029 for heterogeneity test). Further interactive analyses also detected a significant multiplicative interaction between rs824248 and prepregnancy BMI for the risk of GDM (p = 0.041). These findings indicate that LINGO2 rs824248 may serve as a susceptibility marker for GDM in Chinese females.     

Correlation between polymorphisms in IGF2/H19 gene locus and epithelial ovarian cancer risk in Chinese population

To investigate the association between SNPs in human IGF2/H19 gene locus and epithelial ovarian cancer (EOC) risk, we performed a case-control study in 422 individuals (219 EOC patients and 203 cancer-free controls). Four SNPs (rs2525885, rs2839698, rs3741206, rs3741219) were found to be related with EOC risk. Specifically, the minor allele C of rs2525885 and allele A of rs2839698 was associated with elevated EOC genetic susceptibility under both dominant and recessive models (TC + CC vs TT: adjusted OR: 1.61, P = .031; CC vs TT + TC: adjusted OR: 4.87, P = .014; GA + AA vs GG: adjusted OR: 1.63, P = .023; AA vs GG + GA: adjusted OR: 2.43, P = .007). For rs3741206, the genotype TC + CC was associated with a significant decrease in EOC risk with the TT genotype as reference in a dominant genetic model (adjusted OR: 0.44, P = .003), while for rs3741219, genotype AA was associated with a 59% decrease in EOC risk only in the recessive model (adjusted OR: 0.41, P = .038). In the stratified analysis, an increased risk associated with the variant genotypes was observed in only subjects aged >47 years for rs2525885 (adjusted OR = 2.04, P = .024), rs2839698 (adjusted OR = 2.50, P = .047) and rs3741206 (adjusted OR = 0.37, P = .009), respectively. What's more, the TC + CC genotype of rs2525885 was significantly associated with advanced FIGO stage (III vs II, adjusted OR = 2.73, P = .040).     

Contribution of autophagy-related gene 5 variants to acquired aplastic anemia in Han-Chinese population

Immune-mediated quantitative and qualitative defects of hematopoietic stem/progenitor cells (HSPCs) play a vital role in the pathophysiology of acquired aplastic anemia (AA). Autophagy is closely related to T cell pathophysiology and the destiny of HSPCs, in which autophagy-related gene 5 (ATG5) is indispensably involved. We hypothesized that genetic variants of ATG5 might contribute to AA. We studied six ATG5 polymorphisms in a Chinese cohort of 176 patients with AA to compare with 157 healthy controls. A markedly decreased risk of AA in the recessive models of rs510432 and rs803360 polymorphisms (adjusted odds ratio [OR], 95% confidence interval [CI] = 0.467 [0.236-0.924], P = 0.029 for ATG5 rs510432; adjusted OR [95% CI] = 0.499 [0.255-0.975], P = 0.042 for ATG5 rs803360) was observed. Furthermore, the decreased risk was even more pronounced among nonsevere AA compared with healthy controls under recessive models (adjusted OR [95% CI] = 0.356 [0.141-0.901], P = 0.029 for ATG5 rs510432; adjusted OR [95% CI] = 0.348 [0.138-0.878], P = 0.025 for ATG5 rs803360; adjusted OR [95% CI] = 0.352 [0.139-0.891], P = 0.027 for ATG5 rs473543). Above all, rs573775 can strongly predict the occurrence of newly onset hematological event in patients with AA. Our results indicate that genetic ATG5 variants contributed to AA, which may facilitate further clarifying the underlying mechanisms of AA and making a patient-tailored medical decision.     

Relationship between Interleukin-10 ?1082A/G Polymorphism and Risk of Ischemic Stroke: A Meta-Analysis

Objective

To analyze the association between −1082A/G polymorphism in interleukin-10 (IL-10) gene and ischemic stroke (IS) risk by meta-analysis.

Methods

We carried out a systematic electronic search in PubMed, BIOSIS Previews, Science Direct, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Weipu database and WANGFANG Database. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to assess the strength of the association.

Results

7 studies were included. There was no significant association between IL-10 −1082A/G polymorphism and IS risk under all genetic models in overall estimates (A vs. G: OR = 1.23,95%CI = 0.85–1.79;AA vs. GG: OR = 1.01,95%CI = 0.47–2.19; AG vs. GG: OR = 0.76, 95%CI = 0.38–1.55; AA+AG vs. GG: OR = 0.89,95%CI = 0.46–1.73; AA vs. AG+GG: OR = 1.39, 95%CI = 0.91–2.13). Similarly, no associations were found in subgroup analysis based on ethnicity and source of controls. However, removing the study deviating from Hardy–Weinberg equilibrium (HWE) produced statistically significant associations for overall estimates under recessive model(AA VS. AG+GG OR 1.58, 95% CI 1.04–2.42) and among Asians in all genetic models (A VS.G OR 1.64, 95% CI 1.07–2.53; AA vs. GG OR1.91, 95% CI 1.31–2.80; AG vs. GG OR1.44, 95% CI 1.09–1.91; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01;AA VS. AG+GG OR 1.79, 95% CI 1.07–3.00). Even after Bonferroni correction, the associations were observed still significantly in Asians under the two models (AA vs. GG OR1.91, 95% CI 1.31–2.80, P = 0.0008; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01, P = 0.001).

Conclusion

This meta-analysis indicates that IL10 −1082 A/G polymorphism is associated with IS susceptibility in Asians and the −1082 A allele may increase risk of IS in Asians. Considering the sample size is small and between-study heterogeneity is remarkable, more studies with subtle design are warranted in future.     

Genes in the insulin and insulin-like growth factor pathway and odds of metachronous colorectal neoplasia

Insulin and insulin-like growth factor (IGF) genes are implicated in colorectal carcinogenesis. Gene-by-gene interactions that influence the insulin/IGF pathways were hypothesized as modifiers of colorectal neoplasia risk. We built a classification tree to detect interactions in 18 IGF and insulin pathway-related genes and metachronous colorectal neoplasia among 1,439 subjects pooled from two chemoprevention trials. The probability of colorectal neoplasia was greatest (71.8%) among carriers of any A allele for rs7166348 (IGF1R) and AA genotype for rs1823023 (PIK3R1). In contrast, carriers of any A at rs7166348 (IGF1R), any G for the PIK3R1 variant, and AA for rs10426094 (INSR) had the lowest probability (14.3%). Logistic regression modeling showed that any A at rs7166348 (IGF1R) with the AA genotype at rs1823023 (PIK3R1) conferred the highest odds of colorectal neoplasia (OR 3.7; 95% CI 2.2–6.5), compared with carriage of GG at rs7166348 (IGF1R). Conversely, any A at rs7166348 (IGFR1), any G allele at rs1823023 (PIK3R1), and the AA genotype at rs10426094 (INSR) conferred the lowest odds (OR 0.22; 95% CI 0.07–0.66). Stratifying the analysis by parent study and intervention arm showed highly consistent trends in direction and magnitude of associations, with preliminary evidence of genotype effects on measured IGF-1 levels in a subgroup of subjects. These results were compared to those from multifactor dimensionality reduction, which identified different single nucleotide polymorphisms in the same genes (INSR and IGF1R) as effect modifiers for colorectal neoplasia. These results support a role for genetic interactions in the insulin/IGF pathway genes in colorectal neoplasia risk.     

LIN28A gene polymorphisms modify neuroblastoma susceptibility: A four‐centre case‐control study

Neuroblastoma ranks the most common seen solid tumour in childhood. Overexpression of LIN28A gene has been linked to the development of multiple human malignancies, but the relationship between LIN28A single nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility is still under debate. Herein, we evaluated the correlation of four potentially functional LIN28A SNPs (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) and neuroblastoma susceptibility in 505 neuroblastoma patients and 1070 controls from four independent hospitals in China. The correlation strengths were determined by using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Among these SNPs, rs34787247 G>A exhibited a significant association with increased susceptibility in neuroblastoma (GA vs GG: adjusted OR = 1.30, 95% CI = 1.03‐1.64; AA vs GG: adjusted OR = 2.51, 95% CI = 1.36‐4.64, AA/GA vs GG: adjusted OR = 1.42, 95% CI = 1.12‐1.80, AA vs GG/GA: adjusted OR = 2.39, 95% CI = 1.29‐4.42). Furthermore, the combined analysis of risk genotypes revealed that subjects carrying three risk genotypes (adjusted OR = 1.64, 95% CI = 1.02‐2.63) are more inclined to develop neuroblastoma than those without risk genotype, and so do carriers of 1‐4 risk genotypes (adjusted OR = 1.26, 95% CI = 1.01‐1.56). Stratification analysis further revealed risk effect of rs3811464 G>A, rs34787247 G>A and 1‐4 risk genotypes in some subgroups. Haplotype analysis of these four SNPs yields two haplotypes significantly correlated with increased neuroblastoma susceptibility. Overall, our finding indicated that LIN28A SNPs, especially rs34787247 G>A, may increase neuroblastoma risk.     

Distinct Role of CD86 Polymorphisms (rs1129055, rs17281995) in Risk of Cancer: Evidence from a Meta-Analysis

Background and Purpose

Previous studies concerning the role of CD86 polymorphisms (rs1129055 and rs17281995) in cancer fail to provide compelling evidence. The aim of this study was to investigate the role of common polymorphisms in the risk of cancer by meta-analysis.

Methods

By using the search terms Cluster of Differentiation 86/CD86/B7-2/polymorphism/polymorphisms/cancer, we searched PubMed, Embase, CNKI, and Wanfang and identified four studies for rs1129055 (2137 subjects) and rs17281995 (2856 subjects) respectively. Cancer risk was estimated by odds ratio (OR) and 95% confidence interval (95% CI).

Major Findings

Overall, we observed significant reduced risk of cancer in relation to rs1129055. Compared with the individuals with AA genotype, the individuals with GG genotype appeared to have 62% decreased risk to develop cancer (GG versus AA: OR, 0.62; 95% CI, 0.49–0.79; P_het., 0.996). Similar effects were indicated in the G versus A allele model and the GG versus GA+AA genetic model (OR, 0.83; 95% CI, 0.74–0.93; P_het., 0.987; OR, 0.63; 95% CI, 0.50–0.79; P_het., 0.973). In addition, we found genotypes of rs17281995 had a major effect on overall cancer risk (CC versus GG: OR, 2.38; 95% CI, 1.43–3.95; P_het., 0.433; C versus G: OR, 1.23; 95% CI, 1.06–1.43; P_het., 0.521; CC versus GC+GG: OR, 2.38; 95% CI, 1.45–3.93; P_het., 0.443). The association was also observed in Caucasians and colorectal cancer. No obvious publication bias was detected in this meta-analysis.

Conclusions

These data reveal that rs1129055 may have protective effects on cancer risk in Asians and that rs17281995 is likely to contribute to risk of cancer, particularly colorectal cancer in Caucasians.     

BTNL2 Gene Polymorphism and Sarcoidosis Susceptibility: A Meta-Analysis

Background

Butyrophilin-like 2 (BTNL2) rs2076530 gene polymorphism has been implicated in susceptibility to sarcoidosis. However, results from previous studies are not consistent. To assess the association of BTNL2 polymorphism and sarcoidosis susceptibility, a meta-analysis was performed.

Methods

PubMed, Embase were searched for eligible case-control studies. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Results

Ten studies involving a total of 3303 cases and 2514 controls were included in this meta-analysis. Combined data indicated that BTNL2 rs2076530 polymorphism was associated with sarcoidosis susceptibility in allelic model (A vs. G, OR = 1.59, 95%CI: 1.47–1.72), dominant model (AA + AG vs. GG, OR = 2.10, 95%CI: 1.67–2.65), and recessive model (AA vs. AG + GG, OR = 1.93, 95%CI: 1.49–2.50).

Conclusions

This meta-analysis indicates that BTNL2 rs2076530 polymorphism contributes to the risk of sarcoidosis.     

Association between XPG polymorphisms and stomach cancer susceptibility in a Chinese population

Xeroderma pigmentosum group G (XPG) protein plays an important role in the DNA repair process by cutting the damaged DNA at the 3′ terminus. Previous studies have indicated some polymorphisms in the XPG gene are associated with stomach cancer susceptibility. We performed this hospital‐based case–control study to evaluate the association of four potentially functional XPG polymorphisms (rs2094258 C>T, rs751402 C>T, rs2296147 T>C and rs873601G>A) with stomach cancer susceptibility. The four single nucleotide polymorphisms (SNPs) were genotyped in 692 stomach cancer cases and 771 healthy controls. Logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association of interest. Of the studied SNPs, XPG rs873601G>A polymorphism was found to significantly associate with stomach cancer susceptibility (AA versus GG/AG: OR = 1.31, 95% CI = 1.03–1.66, P = 0.027). Combined analysis of all SNPs revealed that the individuals with two of risk genotypes had a significantly increased stomach cancer risk (OR = 1.52, 95% CI = 1.13–2.06). In the stratification analysis, the association between the rs873601AA genotype and stomach cancer risk was observed in older group (>59 year), as well as patients with non‐cardia stomach cancer. Further combined analysis indicated men, smokers, or non‐drinkers more than one risk genotypes had a significantly increased stomach cancer risk. Our results indicate that XPG rs873601G>A polymorphism may be associated with the risk of stomach cancer. Further prospective studies with different ethnicities and large sample sizes are needed to validate our findings.     

Single Nucleotide Polymorphism 8q24 rs13281615 and Risk of Breast Cancer: Meta-Analysis of More than 100,000 Cases

Background

The onset and progression of breast cancer (BC) is influenced by many factors, including the single nucleotide polymorphism (SNP) rs13281615 at 8q24. However, studies of the potential association between rs13281615 at 8q24 and risk of BC have given inconsistent results. We performed a meta-analysis to address this controversy.

Methods

PubMed, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Two curators independently extracted data, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the strength of the association between rs13281615 at 8q24 and risk of BC.

Results

Fourteen studies are included in the meta-analysis, involving 44,283 cases (5,170 Chinese and 39,113 mixed) and 55,756 controls (5,589 Chinese and 50,167 mixed). The GG and G-allele genotypes of rs13281615 at 8q24 are significantly associated with increased risk of BC (GG vs. AG+AA, OR 1.13, 95% CI 1.08–1.19, P<0.001; G-allele vs. A-allele, OR 1.10, 95% CI 1.06–1.14, P<0.001; GG vs. AA, OR 1.20, 95% CI 1.12–1.29, P<0.001). Conversely, the AA genotype is significantly associated with decreased risk of BC (AA vs. AG+GG, OR 0.89, 95% CI 0.84–0.93, P<0.001).

Conclusion

G-allele genotypes of rs13281615 at 8q24 polymorphism are a risk factor for developing BC, while the AA genotype is a protective factor. Further large and well-designed studies are required to confirm this conclusion.     

The −1082A/G polymorphism in the Interleukin-10 gene and the risk of rheumatoid arthritis: A meta-analysis

A large number of studies have shown that the −1082A/G polymorphism (rs1800896) in the Interleukin-10 gene (IL-10) is implicated in the susceptibility to rheumatoid arthritis (RA). However, the results are inconsistent and inconclusive. The aim of this study is to analyze the association between the −1082A/G polymorphism in the IL-10 gene and the RA risk by meta-analysis. A total of 1480 cases and 1413 controls in 10 case–control studies were included in this meta-analysis. The results indicated that the G allele carriers (GG + GA) had a 25% decreased risk of RA, when compared with the homozygote AA (odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.59–0.93). In the analysis in Europeans, significant decreased risks were associated with the G allele carriers (OR = 0.73 and 95% CI: 0.57–0.93 for GG + GA vs. AA). The results from this meta-analysis provide evidence for the association between the IL-10 −1082A/G polymorphism and the risk of RA. To further evaluate gene × gene and gene × environment interactions between the polymorphisms in the IL-10 gene and RA risk, more studies with large groups of patients are required.     

CYP2D6*4 Allele Polymorphism Increases the Risk of Parkinson’s Disease: Evidence from Meta-Analysis

Background

Many epidemiological studies have been conducted to explore the association between a single CYP2D6 gene polymorphism and Parkinson’s disease (PD) susceptibility. However, the results remain controversial.

Objectives

To clarify the effects of a single CYP2D6 gene polymorphism on the risk of PD, a meta-analysis of all available studies relating to CYP2D6*4 polymorphism and the risk of PD was conducted.

Methods

A comprehensive literature search of PubMed, EMBASE, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2013 was conducted. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) were calculated. Meta-regression, Galbraith plots, subgroup analysis, sensitivity analysis, and publication bias analysis were also performed.

Results

Twenty-two separate comparisons consisting of 2,629 patients and 3,601 controls were included in our meta-analysis. The pooled analyses showed a significant association between CYP2D6*4G/A polymorphism and PD risk in all of the comparisons (A vs. G allele: OR = 1.28, 95% CI = 1.14–1.43, P = 0.001; AA vs. GG: OR = 1.43, 95% CI = 1.06–1.93, P = 0.018; AG vs. GG: OR = 1.22, 95% CI = 1.06–1.40, P = 0.006; AG+AA vs. GG: OR = 1.26, 95% CI = 1.10–1.44, P = 0.001; AA vs. AG+GG: OR = 1.37, 95% CI = 1.02–1.83, P = 0.036). In subgroup analysis stratified by ethnicity, significant associations were also demonstrated in Caucasians but not in Asians. No significant association was found in subgroup analysis stratified by age of onset or disease form.

Conclusions

We concluded that the CYP2D6*4G/A polymorphism denotes an increased genetic susceptibility to PD in the overall population, especially in Caucasians. Further large and well-designed studies are needed to confirm this association.     

miR-499 rs3746444 polymorphism is associated with cancer development among Asians and related to breast cancer susceptibility

To derive a more precise estimation of the relationship between miR-499 rs3746444 polymorphism (A>G) and cancer risk, a meta-analysis was performed. A total of 9 studies including 6,077 cases and 7,199 controls were involved in this meta-analysis. Overall, no significantly elevated cancer risk was associated with miR-499 G allele when all studies were pooled into the meta-analysis (AG vs. AA: OR?=?1.14, 95?% CI?=?0.98–1.32; GG vs. AA: OR?=?1.12, 95?% CI?=?0.95–1.33; dominant model: OR?=?1.13, 95?% CI?=?0.99–1.29; recessive model: OR?=?1.05, 95?% CI?=?0.83–1.33). In the subgroup analysis by ethnicity, significantly increased risk was only found for Asians (dominant model: OR?=?1.22, 95?% CI?=?1.02–1.46). When stratified by study design, no statistically significantly elevated risks were found in hospital-based studies or population-based studies. In the subgroup analysis by cancer type, significant cancer risk change was only found for breast cancer when miR-499 G allele was included (dominant model: OR?=?1.13, 95?% CI?=?1.01–1.26). In conclusion, this meta-analysis suggests that the miR-499 rs3746444 polymorphism (A>G) is a low-penetrant risk factor for cancer development among Asians and may contribute to breast cancer susceptibility.     

Meta-analysis of epidermal growth factor polymorphisms and cancer risk: involving 9,779 cases and 15,932 controls

The epidermal growth factor (EGF) pathway stimulates proliferation and differentiation of epidermal and epithelial tissues, and plays an important role in tumorigenesis. The association between EGF polymorphisms and cancer risk is controversial; thus, we performed this meta-analysis. Overall, 41 case-control studies with 9,779 cases and 15,932 controls were retrieved. We found that EGF +61A/G polymorphism increased overall cancer risk (G allele vs. A allele: OR=1.181, 95% CI=1.077-1.295, P(heterogeneity) < 0.001; GG vs. AA: OR=1.370, 95% CI=1.143-1.641, P(heterogeneity) < 0.001; GG+GA vs. AA: OR=1.175, 95% CI=1.047-1.318, P(heterogeneity) < 0.001). In the stratified analysis by cancer type, the +61?G allele was a risk factor for colorectal cancer, esophageal carcinoma, gastric cancer, and hepatocellular carcinoma. Individuals who carried +61G allele had higher cancer susceptibility in mixed and European racial subgroups. An increased association was detected in the hospital-based subgroup. No significant association was found among EGF -1380A/G, -1744G/A, rs6983267T/G polymorphisms and cancer risk.