CXCL12 G801A polymorphism and breast cancer risk: a meta-analysis

The G801A polymorphism in the CXCL12 gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Five published case–control studies, including 1,058 breast cancer cases and 1,023 controls were identified. No study had a deviation from the Hardy–Weinberg equilibrium (HWE) in controls. We found that the CXCL12 G801A (rs1801157) polymorphism was associated with a significantly increased risk of breast cancer risk when all studies were pooled into the meta-analysis (codomiant model: AA versus GG, OR = 1.64, 95% CI = 1.16–2.33; GA versus GG, OR = 1.42, 95% CI = 1.18–1.71; dominant model: AA/GA versus GG, OR = 1.44, 95% CI = 1.21–1.72). Furthermore, Egger’s test did not show any evidence of publication bias (P > 0.05 for the dominant model). In conclusion, the results suggest that the CXCL12 G801A polymorphism may be a low-penetrant risk factor for developing breast cancer.     

Association of a LSP1 gene rs3817198T>C polymorphism with breast cancer risk: evidence from 33,920 cases and 35,671 controls

Published data on the association between lymphocyte-specific protein 1 (LSP1) rs3817198T>C polymorphism and breast cancer risk are inconclusive. Hence, we conducted a meta-analysis of the LSP1 gene and risk of breast cancer to obtain the most reliable estimate of the association. PubMed, Embase and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between the LSP1 rs3817198T>C polymorphism and risk of breast cancer. A total of seven eligible studies including 33,920 cases and 35,671 controls based on the search criteria were involved in this meta-analysis. The distributions of genotypes in the controls were all in agreement with Hardy–Weinberg equilibrium. We observed that the LSP1 rs3817198T>C polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.06, 95% CI = 1.04–1.08; the homozygote codominant: OR = 1.14, 95% CI = 1.01–1.28). In the stratified analysis by ethnicity, significant association was observed in Caucasians for CC versus TT homozygote codominant model (OR = 1.25; 95% CI = 1.03–1.52) and for the recessive model (OR = 1.22; 95% CI = 1.02–1.47). There was significant association observed in Africans for CC versus TT homozygote codominant model (OR = 0.45; 95% CI = 0.22–0.92) and for the recessive model (OR = 0.43; 95% CI=0.22–0.88). Also, significant association was observed in mixed ethnicities for CC versus TT homozygote codominant model (OR = 1.12; 95% CI = 1.05–1.19). When stratified by study design, statistically significantly elevated risk was found in nested case–control studies (CC vs. TT: OR = 1.12, 95% CI = 1.05–1.19). But no significant association was observed for all comparison models between LSP1 rs3817198T>C polymorphism and breast cancer risk in hospital-based and people-based studies. When stratified by BRCA1 mutation carriers status, statistically significantly elevated risk was found in this meta-analysis (the allele contrast model: OR = 1.07, 95% CI = 1.01–1.14; the dominant model: OR = 1.09, 95% CI = 1.00–1.18). And significant association was found in the BRCA2 mutation carriers in the allele contrast (OR = 1.11, 95% CI = 1.03–1.20), the homozygote codominant (OR = 1.23, 95% CI = 1.04–1.47), the heterozygote codominant (OR = 1.12, 95% CI = 1.00–1.25) and the dominant models (OR = 1.14, 95% CI = 1.03–1.27). There was significant association between LSP1 rs3817198T>C polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort in all comparison models (the allele contrast model: OR = 1.08, 95% CI = 1.03–1.13; CC vs. TT: OR = 1.16, 95% CI = 1.05–1.29; TC vs. TT: OR = 1.09, 95% CI = 1.01–1.16; the dominant model: OR = 1.10, 95% CI = 1.03–1.17; the recessive model: OR = 1.12, 95% CI = 1.01–1.23). In conclusion, this meta-analysis suggests that the LSP1 rs3817198T>C polymorphism is a low-penetrant risk factor for developing breast cancer but may not be in Africans.     

Polymorphisms of Glucose-Regulated Protein 78 and Risk of Colorectal Cancer: A Case-Control Study in Southwest China

Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum chaperone, up-regulation serves as an efficient mechanism to promote malignant transformation of colorectal cancer (CRC) and protect CRC cells against apoptosis. Recently, the analysis of GRP78 polymorphisms has already determined that GRP78 rs391957 polymorphism could predict clinical outcome in CRC patients. Thus, we tested whether GRP78 polymorphisms are related to the risk of CRC. In this study, we detected two GRP78 polymorphisms (rs391957 (C>T) and rs430397 (G>A)) in 414 CRC cases and 502 hospital-based cancer-free healthy controls in Southwest China using a polymerase chain reaction–restriction fragment length polymorphism technique. Compared with the CC genotype, carriers of CT and TT genotypes of rs391957 polymorphism had higher risks of CRC (odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.06–1.83 for CT genotype and OR = 2.10, 95% CI = 1.06–4.14 for TT genotype, respectively). In CRC cases, the variant T allele was significantly associated with tumor invasion stage (P = 0.030), but not with status of lymph nodes metastasis (P = 0.052). Compared with the GG genotype, carriers of GA and AA genotypes of rs430397 polymorphism had higher risks of CRC (OR = 1.63, 95% CI = 1.23–2.15 for GA genotype and OR = 2.92, 95% CI = 1.23–6.94 for AA genotype, respectively). The rs430397 polymorphism was not associated with the clinicopathological characteristics of CRC. These data provide the first evidence that GRP78 rs391957 and rs430397 polymorphisms could serve as markers to predict the risk of CRC.     

Association between MLH1 -93G>A Polymorphism and Risk of Colorectal Cancer

Background

The -93G>A (rs1800734) polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC) risk. However, the results remain conflicting rather than conclusive.

Objective

The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC.

Methods

To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls) was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI) status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC.

Results

The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01–1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01–1.11). This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94–3.28; AG versus GG: OR = 1.29, 95% CI = 1.10–1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24–1.68; AA versus AG/GG: OR = 2.29, 95% CI = 1.78–2.96). Egger’s test did not show any evidence of publication bias.

Conclusion

Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.     

Association of Polymorphism rs198977 in Human Kallikrein-2 Gene (KLK2) with Susceptibility of Prostate Cancer: A Meta-Analysis

ObjectivesTo assess the association of polymorphism rs198977 in the human kallikrein-2 gene (KLK2) and risk of prostate cancer (PCa).MethodsTwo investigators independently searched the PubMed, Elsevier, EMBASE, Web of Science, Wiley Online Library and Chinese National Knowledge Infrastructure (CNKI). Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for rs198977 and PCa were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate.ResultsSix studies met the inclusion criteria in this meta-analysis, which included 5859 PCa cases and 4867 controls. Overall, rs198977 was associated with the PCa risk (TT+CT vs. CC, pooled OR = 1.163, 95% CI = 1.076–1.258, P-value <0.0001). When stratified by ethnicity, significant association was observed in Caucasian samples under both allele comparison (T vs. C, pooled OR = 1.152, 95% CI = 1.079–1.229, P-value <0.0001) and dominant model (TT+CT vs. CC, pooled OR = 1.197, 95% CI = 1.104–1.297, P-value <0.0001). In the overall analysis, a comparably significant increase in the frequency of allele T for rs198977 was detected between cases and controls in Caucasian.ConclusionThis meta-analysis suggests that rs198977 of KLK2 was associated with susceptibility of PCa in Caucasian and the allele T might increase the risk of PCa in Caucasian.     

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.     

Meta-analysis of TYK2 gene polymorphisms association with susceptibility to autoimmune and inflammatory diseases

The aim of our meta-analysis was to quantitatively summarize the association of TYK2 gene polymorphisms with autoimmune and inflammatory diseases. 11 studies that included data from 21497 cases and 22647 controls were identified. OR was used as a measure of the effect of the association in a fixed/random effect model. Meta-analysis was performed for six TYK2 gene polymorphisms (rs34536443, rs2304256, rs280523, rs280519, rs12720270 and rs12720356). Significant association was found in rs34536443 (C versus G: OR = 0.76, 95% CI = 0.69–0.84, P < 0.00001; GC + CC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0005; CC versus GG + GC: OR = 0.76, 95% CI = 0.28–2.05, P = 0.58; CC versus GG: OR = 0.74, 95% CI = 0.27–2.02, P = 0.56; GC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0006) and rs2304256 (A versus C: OR = 0.78, 95% CI = 0.70–0.87, P < 0.0001; CA + AA versus CC: OR = 0.69, 95% CI = 0.59–0.81, P < 0.0001; AA versus CC + CA: OR = 0.75, 95% CI = 0.66–1.00, P = 0.05; AA versus CC: OR = 0.64, 95% CI = 0.47–0.86, P = 0.003; CA versus CC: OR = 0.70, 95% CI = 0.60–0.83, P < 0.0001) in TYK2 gene, but not for the other polymorphisms (rs280523, rs280519, rs12720270, and rs12720356). This meta-analysis demonstrates that autoimmune and inflammatory diseases is associated with TYK2 gene rs34536443 and rs2304256 polymorphisms, but not rs280523, rs280519, rs12720270 and rs12720356.     

Associations between interleukin-10 polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis

The aim of this study was to determine whether the interleukin-10 (IL-10) polymorphisms confer susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the IL-10 −1082 G/A, −592 C/A, −892 C/T and IL-10.R polymorphisms and RA using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 16 studies (19 comparisons) involving 2647 RA patients and 3383 controls were considered in the meta-analysis. Meta-analysis of the IL-10 −1082 G/A polymorphism showed no association with RA in the study subjects, or in European or Asian subjects. However, meta-analysis of the −1082 G allele in 4 studies in Hardy–Weinberg equilibrium showed a significant association with RA (OR = 1.217, 95% CI = 1.027–1.442, P = 0.0236). In contrast, meta-analysis of the C allele, the CC genotype, and of the CC versus the AA genotype of the IL-10 −592 C/A polymorphism showed significant associations with RA. The overall ORs of the associations between the C allele and RA were 0.684 and 0.758 (95% CI = 0.494–0.946, P = 0.022; 95% CI = 0.475–1.210, P = 0.045) in all study subjects and Asians. Meta-analysis of the CC + CT versus TT genotype and of the CC versus TT genotype of the IL-10 −892 C/T polymorphism revealed significant associations with RA. The overall OR of the association between the C allele carrier and RA was 0.552 (95% CI = 0.375–0.812, P = 0.003). No association was found between the IL10.R2 alleles and RA. This meta-analysis suggests that the IL-10 −592 C/A polymorphism confers susceptibility to RA in Asians and that the IL-10 −1082 G/A and −892 C/T polymorphisms are associated with RA susceptibility. These findings suggest the IL-10 genes confer susceptibility to RA.     

Association between CASP8 –652 6N Del Polymorphism (rs3834129) and Colorectal Cancer Risk: Results from a Multi-Centric Study

The common −652 6N del variant in the CASP8 promoter (rs3834129) has been described as a putative low-penetrance risk factor for different cancer types. In particular, some studies suggested that the deleted allele (del) was inversely associated with CRC risk while other analyses failed to confirm this. Hence, to better understand the role of this variant in the risk of developing CRC, we performed a multi-centric case-control study. In the study, the variant −652 6N del was genotyped in a total of 6,733 CRC cases and 7,576 controls recruited by six different centers located in Spain, Italy, USA, England, Czech Republic and the Netherlands collaborating to the international consortium COGENT (COlorectal cancer GENeTics). Our analysis indicated that rs3834129 was not associated with CRC risk in the full data set. However, the del allele was under-represented in one set of cases with a family history of CRC (per allele model OR = 0.79, 95% CI = 0.69–0.90) suggesting this allele might be a protective factor versus familial CRC. Since this multi-centric case-control study was performed on a very large sample size, it provided robust clarification of the effect of rs3834129 on the risk of developing CRC in Caucasians.     

The association of polymorphisms on TGFBR1 and colorectal cancer risk: a meta-analysis

Epidemiological studies found inconsistent results on the association of two variants on TGFBR1 (TGFBR1*6A and Int7G24A) with colorectal cancer (CRC) risk. The present study was aimed to evaluate the association of these two variants with CRC susceptibility via the meta-analysis methods. For variant TGFBR1*6A, nine reports including 6,765 CRC patients and 8,496 unrelated controls were identified. The heterozygotes *6A/*9A showed a significant increased risk of CRC with the pooled OR was 1.12 (95% CI = 1.02–1.23), and the pooled OR for the homozygotes *6A/*6A was 1.13 (95% CI = 0.80–1.58) compared to the homozygotes *9A/*9A. However, under the dominant effect model, the TGFBR1*6A carriers showed a significantly increased CRC risk (pooled OR = 1.12, 95% CI = 1.03–1.23, *6A/*6A and *6A/*9A vs. *9A/*9A). For variant Int7G24A, three case–control studies with 1,074 cases and 1,945 controls were found. Although no significant association was found for heterozygosity Int7G24A carriers with CRC risk (pooled OR = 0.97, 95% CI = 0.67–1.42), the homozygosity A/A carriers showed a significant elevated risk of CRC (pooled OR = 1.68, 95% CI = 1.14–2.47) compared to G/G homozygotes. Under the recessive effect model, homozygotes A/A showed a 71% increase of CRC risk compared to the A/G and G/G genotype carriers (pooled OR = 1.71, 95% CI = 1.17–2.51). These data strongly suggested that the two polymorphisms of TGFBR1 may confer low-penetrance susceptibility of CRC risk.     

A Meta-Analysis of PTGS1 and PTGS2 Polymorphisms and NSAID Intake on the Risk of Developing Cancer

Background

Several studies have investigated whether the polymorphisms in the prostaglandin endoperoxide synthase 1 (PTGS1) and PTGS2 genes and nonsteroidal anti-inflammatory drug (NSAID) use are associated with cancer risk; however, those studies have produced mixed results. Therefore, we performed a meta-analysis to evaluate the association between the PTGS1 and PTGS2 polymorphisms and the effect of NSAID use on the risk of developing cancer.

Methods

We conducted a comprehensive search in PubMed through March 2012. The odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated using the fixed-effect model or the random-effect model.

Results

The database search generated 13 studies that met the inclusion criteria. For PTGS1 rs3842787, NSAID users homozygous for the major allele (CC) had a significantly decreased cancer risk compared with non-NSAID users (OR = 0.73, 95% CI = 0.59–0.89). For PTGS2 rs5275 and rs20417, there were no significant differences between the gene polymorphism and NSAID use on cancer risk among the 8 and 7 studies, respectively. However, in the stratified analysis by the type of cancer or ethnicity population, NSAID users homozygous for the major allele (TT) in rs5275 demonstrated significantly decreased cancer risk compared with non-NSAID users in cancer type not involving colorectal adenoma (OR = 0.70, 95% CI = 0.59–0.83) and among the USA population (OR = 0.67, 95% CI = 0.56–0.82). NSAID users homozygous for the major allele (GG) in rs20417 displayed a significantly decreased cancer risk than non-NSAID users among the US population (OR = 0.72, 95% CI = 0.58–0.88). For the PTGS2 rs689466 and rs2745557 SNPs, there were no significant differences.

Conclusion

This meta-analysis suggests that the associations between PTGS polymorphisms and NSAID use on cancer risk may differ with regard to the type of cancer and nationality.     

Interleukin‐8 ‐251A/T gene polymorphism and lung cancer susceptibility: a meta‐analysis

Many studies have examined the association between the interleukin‐8 ‐251T/A ( rs4073 ) gene polymorphism and lung cancer risk in various populations, but the results have been inconsistent. In this meta‐analysis, PubMed was searched for case–control studies published through 01 December 2013. The data were extracted, and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. We assessed six published studies on the association between the interleukin‐8 ‐251T/A polymorphism and lung cancer risk. The included studies yielded a total of 3265 lung cancer cases and 3607 controls. For the homozygous A/A and A allele carriers (T/A + A/A), the pooled ORs for all studies combining 3265 cases and 3607 controls were 1.03 (95% CI = 0.92–1.14; P = 0.235 for heterogeneity) and 1.07 (95% CI = 0.96–1.19; P = 0.245 for heterogeneity) when compared with the homozygous wild‐type genotype (T/T). When the analysis was stratified by ethnicity, significant risks were found among Asians for both the A allele carriers and the homozygous A/A individuals. However, no significant associations were found in non‐Asian populations using any of the genetic models. This meta‐analysis suggests that the interleukin‐8 ‐251A allele confer an increased risk for the development of lung cancer among Asians.     

MDM2 SNP309 polymorphism and breast cancer risk: a meta-analysis

The mouse double minute 2 (MDM2) gene encodes a phosphoprotein that interacts with P53 and negatively regulates its activity. SNP309 polymorphism (T-G) in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Many published studies have evaluated the association between MDM2 SNP309 polymorphism and breast cancer risk. However, the results were inconsistent. We combined and analyzed the data from 19 case–control studies including 14,450 cases and 13,382 controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association between MDM2 SNP309 polymorphism and breast cancer risk. No significant association was found in all genetic models in overall population. However, in subgroup analysis by ethnicity (4 studies in Asian group, 13 studies in European group, 2 studies of mixed population which were separated into 2 European population group and 2 African population group), we found an increased breast cancer susceptibility for GT versus TT (OR = 1.31, 95% CI = 1.03–1.67) in Asian population and for GT versus TT (OR = 1.31, 95% CI = 1.03–1.66) in African population. When stratified by family history status (5 studies in familial breast cancer group, 5 studies in sporadic breast cancer group), homozygous subjects of sporadic breast cases carrying the T309G G allele exhibited elevated breast cancer risk (OR = 1.35, 95% CI = 1.00–1.82), whereas heterozygous carriers did not show significant association with breast cancer risk for GT vs. TT (OR = 1.26, 95% CI = 0.84–1.87). Our meta–analysis suggests that MDM2 SNP309 polymorphism may increase the risk to breast cancer in Asian and African population.     

Mitogen/extracellular signal-regulated kinase kinase-5 promoter region polymorphisms affect the risk of sporadic colorectal cancer in a southern Chinese population

Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5), which belongs to a network of mitogen-activated protein kinase pathways, play a pivotal role in carcinogenesis. The purpose of this study was to investigate whether variants in the MEK5 gene promoter were involved in susceptivity of individuals to sporadic colorectal cancer (CRC). In the present hospital-based case-control study of 737 patients with sporadic CRC and 703 healthy control subjects in a southern Chinese population, the two polymorphisms of MEK5 promoter (i.e., rs7172582C>T and rs3743354T>C) were genotyped by TaqMan assay. There were significant differences between cases and controls in the genotype and allele distribution of the MEK5 gene rs3743354T>C polymorphism. The rs3743354 CC genotype was associated with a significantly decreased risk of CRC when compared with the TT genotype (adjusted odds ratios [ORs]=0.43; 95% confidence interval [CI], 0.24-0.77). Compared to the T allele, a significant correlation was detected between the presence of the C allele and decreased risk of CRC (adjusted OR=0.79; 95% CI, 0.61-0.94). The decreased risk of CRC associated with rs3743354 variant genotypes (i.e., CT+CC) was found in the smoker subgroup (adjusted OR=0.63; 95% CI=0.45-0.88). Further, environmental factors, including smoking and drinking, interacted with rs3743354C variant genotypes to reduce CRC risk. Western blot analysis showed that the levels of MEK5 protein in sporadic CRC neoplastic tissues and adjacent normal colorectal epithelium tissues were lower in the carriers of rs3743354 CC genotypes than that in those with rs3743354 TT genotypes or those with rs3743354 TC genotypes. However, no significant association was found between the rs7172582C>T polymorphism and risk of CRC. These data indicate that the rs3743354 polymorphism in the MEK5 promoter may affect the risk of developing CRC.     

Meta-analysis supports association of a functional SNP (rs1801133) in the MTHFR gene with Parkinson's disease

The MTHFR is a candidate risk gene for Parkinson's disease (PD), and a functional SNP (rs1801133) in the coding region of this gene has been investigated for the associations with the illness extensively among worldwide populations, but overall the results were inconsistent. Here, to assess the relationship between rs1801133 and risk of PD in general populations, we conducted a systematic meta-analysis by combining all available case–control samples in European and Asian populations, with a total of 1820 PD cases and 7530 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for rs1801133 and PD were calculated using the Mantel–Haenszel method with a fixed-effect model. Overall, rs1801133 was significantly associated with the risk of PD (allelic model, pooled OR = 1.212 for T allele, 95% CI = 1.097–1.340, p-value = 0.0002). When stratifying for ethnicity, significant association was also observed in European (allelic model, pooled OR = 1.187 for T allele, 95% CI = 1.058–1.332, p-value = 0.004) and Asian samples (allelic model, pooled OR = 1.293 for T allele, 95% CI = 1.058–1.580, p-value = 0.012) respectively. In addition, rs1801133 was also significantly associated with MTHFR mRNA expression in both CEU (European, p-value = 0.0149) and CHB (Chinese, p-value = 0.0178) HapMap populations. Collectively, our meta-analysis suggests that rs1801133 is significantly associated with susceptibility to PD in European and Asian populations, and MTHFR is likely an authentic risk gene for PD.     

Genetic association study of intron variants in the forkhead box protein P3 gene in Chinese patients diagnosed with cervical cancer

The aim of this study was to investigate the effects of forkhead box protein P3 (FOXP3) intron single nucleotide variants (SNVs) in high‐risk human papilloma virus (HR‐HPV) infection and cervical cancer (CC) malignant lesions. We performed FOXP3 genotyping in 350 patients with CC and 350 healthy controls using the ImLDR multiple single nucleotide polymorphism genotyping technology. The heterozygous mutation TC in rs2294021 decreased the risk of HR‐HPV infection and CC malignant lesions (TC vs. TT: OR = 0.71, 95% CI = 0.51–0.99); the dominant model TC+CC and allele C in rs2294021 decreased the risk of CC malignant lesions (TC+CC vs. TT: OR = 0.69, 95% CI = 0.50–0.95; C vs. T: OR = 0.78, 95% CI = 0.63–0.97). The heterozygous mutation GA, dominant model GA+AA and allele A in rs3761549 also decreased the risk of HR‐HPV infection and CC malignant lesions (GA vs. GG: OR = 0.70, 95% CI = 0.51–0.96; GA+AA vs. GG: OR = 0.69, 95% CI = 0.51–0.94; A vs. G: OR = 0.75, 95% CI = 0.58–0.96). Patients with CC and HR‐HPV infection carrying rs2294021 TC and rs3761549 GA had lower expression of FOXP3 protein. Haplotype analysis revealed that T‐C‐A decreased the risk of HR‐HPV infection. Furthermore, we found a significant association between immune cells infiltration and prognosis in patients with CC. Our findings demonstrated that rs2294021 and rs3761549 variants may protect against HR‐HPV and CC malignant lesions by downregulating FOXP3 and that FOXP3 was associated with immune cells infiltration, which affected the prognosis of CC.     

A common variant in the adiponectin gene and polycystic ovary syndrome risk

In this study, we explored whether polymorphisms in insulin receptor (INSR), adiponectin (ADIPOQ), parathyroid hormone (PTH), and vitamin D receptor (VDR) genes are associated with polycystic ovary syndrome (PCOS). A total of 362 subjects, including 181 women with PCOS and 181 controls were enrolled in this case-control study. Two SNPs (rs2059806 and rs1799817) in the INSR gene, two SNPs (rs2241766 and rs1501299) in the ADIPOQ gene, one SNP (rs6256) in the PTH gene, and one SNP (rs757343) in the VDR gene were analyzed using PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between the women with PCOS and controls for the rs2059806, rs1799817, rs1501299, rs6256, and rs757343 polymorphisms either before or after adjustment for confounding factors including age and BMI. However, the ADIPOQ rs2241766 “TT” genotype compared with “TG and GG” genotypes was associated with a 1.93-fold increased risk for PCOS (P = 0.006, OR = 1.93, 95% CI = 1.20–3.11), and the differences remained significant after adjustment for age and BMI (P = 0.039, OR = 1.72, 95% CI = 1.03–2.86). Furthermore, the ADIPOQ rs2241766 “T” allele was significantly overrepresented in women with PCOS than controls (P = 0.006; OR = 1.80, 95% CI = 1.18–2.70), and the difference remained significant after Bonferroni correction. Our findings suggest that the ADIPOQ rs2241766 “TT” genotype is a marker of increased PCOS susceptibility. This study also indicates for the first time that there are no significant association between INSR rs2059806, PTH rs6256, and VDR rs757343 gene polymorphisms and PCOS risk. However, these data remain to be confirmed in larger studies and in other populations.     

Association of thrombospondin 1 gene with schizophrenia in Korean population

Thrombospondin 1 (THBS1), a multi-domain glycoprotein, is secreted from astrocytes and promotes synaptogenesis. Increasing evidence has suggested that not only various markers for synaptic pathology, but also astrocytes are affected in schizophrenia. In this study, we investigated whether coding region single nucleotide polymorphisms (cSNPs) of the THBS1 gene were associated with schizophrenia and with the clinical symptoms of schizophrenia patients. We genotyped two cSNPs [rs2228261 (Asn470Asn) and rs2292305 (Thr523Ala)] using direct sequencing in 220 schizophrenia patients and 376 control subjects. In this study, rs2228261 revealed significant association with schizophrenia in both codominant (TT vs. CC, P = 0.009, OR = 2.10, 95% CI = 1.23–3.59) and recessive models (TT vs. CC/CT, P = 0.0012, OR = 2.28, 95% CI = 1.38–3.77). Also, rs2292305 was associated with schizophrenia in the recessive model (GG vs. AA/AG, P = 0.0052, OR = 2.05, 95% CI = 1.24–3.38). Additionally, in the analysis of the haplotype, the CA and TG haplotypes consisting of rs2228261 and rs2292305 were associated with schizophrenia in the dominant (P = 0.019, OR = 1.79, 95% CI = 1.10–2.90) and recessive models, respectively (P = 0.0086, OR = 0.51, 95% CI = 0.31–0.84). In further analysis according to the clinical symptoms, rs2292305 showed a weak association with the poor concentration symptoms of schizophrenia patients in the dominant model (AG/GG vs. AA, P = 0.024, OR = 2.04, 95% CI = 1.09–3.83). The results suggest that the THBS1 gene may contribute to the susceptibility of schizophrenia.     

The functional −94 insertion/deletion ATTG polymorphism in the promoter region of NFKB1 gene increases the risk of sporadic colorectal cancer

Objective: To investigate the allele and genotype frequencies of NFKB1 ?94 ins/del ATTG (rs28720239) polymorphism and to evaluate the association between the polymorphism and colorectal cancer (CRC) risk in Malaysian population. Methods: Genomic DNA was extracted from the peripheral blood samples of 474 study subjects, which consisted of 237 histopathologically confirmed CRC patients and an equal number of cancer-free controls. The NFKB1 ?94 ins/del ATTG (rs28720239) polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed by DNA sequencing. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Results: The frequencies of wildtype (del/del), heterozygous (del/ins) and variant (ins/ins) genotypes in CRC patients were 31.7%, 53.6% and 14.8%, respectively, while those in cancer-free controls were 35.0%, 58.2% and 6.8%, respectively. The frequency of the variant genotype was significantly higher in cases compared to controls (P < 0.01). Evaluation of the risk association of the polymorphic genotypes revealed that the variant genotype could contribute to a significantly increased risk of CRC (OR = 2.42, 95% CI = 1.24–4.73, P < 0.01). Conclusions: The variant allele of NFKB1 ?94 ins/del ATTG (rs28362491) polymorphism is associated with higher risk of sporadic CRC in Malaysian population.     

CYP2E1 Rsa I/Pst I polymorphism contributes to oral cancer susceptibility: a meta-analysis

Previous data on association between CYP2E1 Rsa I/Pst I polymorphism and oral cancer risk were controversial. To investigate the association between CYP2E1 Rsa I/Pst I polymorphism and oral cancer risk. We performed a meta-analysis to assess the relationship between oral cancer and genotype with English language until June 2010. Twelve published case–control studies of 1259 patients with oral cancer and 2262 controls were acquired. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association in codominant and dominant models. Overall, the pooled ORs indicated a significant association between CYP2E1 Rsa I/Pst I polymorphism and oral cancer risk (for c1/c2 vs. c1/c1: OR = 1.30, 95% CI = 1.04–1.62, P_{heterogeneity} = 0.57; for (c1/c2 + c2/c2) vs. c1/c1: OR = 1.32, 95% CI = 1.07–1.64, P_{heterogeneity} = 0.57, respectively). In subgroup analysis by race, the same significant risks were found among Asian (for c1/c2 vs. c1/c1: OR = 1.41, 95% CI = 1.05–1.91, P_{heterogeneity} = 0.92; for (c1/c2 + c2/c2) vs. c1/c1: OR = 1.43, 95% CI = 1.08–1.88, P_{heterogeneity} = 0.97, respectively). In conclusion, this meta-analysis demonstrates that CYP2E1 Rsa I/Pst I c2 allele may be a biomarker for oral cancer, especially among Asian populations.