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.     

TNF-α-308G/A Polymorphism Contributes to Obstructive Sleep Apnea Syndrome Risk: Evidence Based on 10 Case-Control Studies

Objective

The aim of our study was to investigate the association between the TNF-α-308G/A polymorphism and obstructive sleep apnea syndrome (OSAS).

Method

The Medline, Web of Science, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Cochrane Central Register of Controlled Trials were searched. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to study TNF-α-308G/A polymorphism and risk of OSAS.

Result

10 case-control studies were included in our meta-analysis. The results from our study showed that the TNF-α-308G/A polymorphism was significantly associated with risk of OSAS (A vs. G: OR = 1.67, 95% CI = 1.43–1.95). In the subgroup analysis by ethnicity, the statistical similar results were observed both in European (A vs. G: OR = 1.68, 95% CI = 1.35–2.08) and Asian population (A vs. G: OR = 2.02, 95% CI = 1.50–2.71). When stratified by age, a significantly increased risk was observed in adult carries A allele compared with G allele (OR = 1.79, 95% CI = 1.50–2.13), whereas no association was found in children (OR = 1.09, 95% CI = 0.70–1.69).

Conclusion

Our study suggested that the TNF-α- 308G/A polymorphism contributed to the susceptibility to the risk of OSAS. Additional well-designed large studies are needed to validate our findings.     

Vascular Endothelial Growth Factor Genotypes and Haplotypes Contribute to the Susceptibility of Obstructive Sleep Apnea Syndrome

Background

To investigate whether VEGF polymorphisms (-460T/C, +405G/C, and +936C/T)/haplotypes influence the susceptibility of obstructive sleep apnea (OSA).

Method

A prospective case-control study was conducted to evaluate the genetic effects of VEGF polymorphisms on the development of OSA. 150 patients and 225 healthy controls were recruited for this study and their genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression analysis.

Result

Our study showed that the -460C allele (C vs. T: OR = 1.95, 95% CI = 1.38–2.76) and +936T allele (T vs. C: OR = 1.48, 95% CI = 1.02–2.15) were associated with an increased OSA risk, whereas +405C allele was associated with a decreased susceptibility to OSA (C vs. G: OR = 0.61, 95% CI = 0.45–0.83). Compared with the most common haplotype CCT, CGC (OR = 2.22, 95% CI = 1.19–4.13) and TGC (OR = 3.83, 95% CI = 1.56–9.40) were associated with a significantly increased risk of OSA.

Conclusion

These observations implied that VEGF gene polymorphisms might be associated with the susceptibility to OSA. These results need to be validated by other independent studies, especially in diverse ethnic populations.     

PAI-1 4G/5G Polymorphism Contributes to Cancer Susceptibility: Evidence from Meta-Analysis

Background

The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results.

Methods

A meta-analysis based on 25 case-control studies was performed to address this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with I² test.

Results

Overall, a significant increased risk of cancer was associated with the PAI-1 4G/4G polymorphism for the allele contrast (4G vs. 5G: OR = 1.10, CI = 1.03–1.18, I² = 49.5%), the additive genetic model (4G/4G vs. 5G/5G: OR = 1.21, CI = 1.06–1.39, I² = 51.9%), the recessive genetic model (4G/4G vs. 4G/5G+5G/5G: OR = 1.11, CI = 1.04–1.18, I² = 20.8%). In the subgroup analysis by ethnicity, the results indicated that individuals with 4G/4G genotype had a significantly higher cancer risk among Caucasians (4G/4G vs. 5G/5G: OR = 1.31, 95%CI = 1.09–1.59, I² = 59.6%; 4G/4G vs. 4G/5G: OR = 1.12, 95%CI = 1.04–1.21, I² = 3.6%; recessive model: OR = 1.12, 95%CI = 1.05–1.21, I² = 25.3%).

Conclusions

The results of the present meta-analysis support an association between the PAI-1 4G/5G polymorphism and increasing cancer risk, especially among Caucasians, and those with 4G allele have a high risk to develop colorectal cancer and endometrial cancer.     

Pre-miR-27a rs895819A/G Polymorphisms in Cancer: A Meta-Analysis

Background

MicroRNAs (miRNAs) negatively regulate the 3′ untranslated region (3′-UTR) of coding genes by suppressing translation or degrading mRNAs, and they act as oncogenes or tumor suppressors. Recently, several studies investigated the association between pre-miR-27a rs895819 polymorphism and the risks of various cancers, but the results were inconsistent.

Methodology/Principal Findings

We conducted a meta-analysis of 13 studies that included 6501 cancer cases and 7571 controls to address this association. Overall, this meta-analysis showed that the pre-miR-27a rs895819 A/G polymorphism was not statistically associated with cancers risk in all genetic models. In the stratified analysis by cancer types, when compared with the ancestral A allele, individuals with the variant G allele was consistently associated with reduced risks of breast cancer (OR = 0.92, 95% CI = 0.85–0.99), renal cell cancer (OR = 0.81, 95% CI = 0.67–0.97) and nasopharyngeal cancer (OR = 0.84, 95% CI = 0.72–0.97). Inversely, individuals with the heterozygote AG was associated with an increased risk of digestive tract cancers compared with AA genotype (AG vs. AA: OR = 1.16, 95% CI = 1.01–1.32). In the stratified analysis by ethnicity, the pre-miR-27a rs895819 polymorphism showed statistically significant association with decreased risks of cancers in Caucasians (G vs. A allele: OR = 0.90, 95% CI = 0.83–0.97; AG vs. AA: OR = 0.84, 95% CI = 0.75–0.94; AG/GG vs. AA: OR = 0.85, 95% CI = 0.76–0.94) but not in Asians.

Conclusion/Significance

This meta-analysis suggests that the pre-miR-27a rs895819 polymorphism may contribute to the susceptibilities of some specific-type of cancers, including breast cancer, renal cell cancer, nasopharyngeal cancer and digestive tract cancers, as well as the susceptibilities of cancers in Caucasians to some extent.     

Association between Methylenetetrahydrofolate Reductase C677T Polymorphism and Susceptibility to Cervical Cancer: A Meta-Analysis

Background

To assess the association between MTHFR polymorphism and cervical cancer risk, a meta-analysis was performed.

Methods

Based on comprehensive searches of the PubMed, Embase, and Web of Science databases, we identified outcome data from all articles estimating the association between MTHFR polymorphism and cervical cancer risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.

Results

A total of 12 studies with 2,924 cases (331 cervical intraepithelial neoplasia (CIN) I, 742 CIN II/III, 1851 invasive cervical cancer) and 2,581 controls were identified. There was no significant association between MTHFR C677T polymorphism and CIN I risk (T vs. C, OR = 1.10, 95% CI = 0.92–1.31; TT vs. CC, OR = 1.14, 95% CI = 0.78–1.68; TT+CT vs. CC, OR = 1.22, 95% CI = 0.94–1.58; TT vs. CT+CC, OR = 0.99, 95% CI = 0.70–1.40). For the CIN II/III, lack of an association was also found (T vs. C, OR = 1.08, 95% CI = 0.95–1.23; TT vs. CC, OR = 1.15, 95% CI = 0.87–1.52; TT+CT vs. CC, OR = 1.13, 95% CI = 0.94–1.35; TT vs. CT+CC, OR = 1.07, 95% CI = 0.83–1.38). The T allele had significant association to susceptibility of invasive cervical cancer in recessive model (TT vs. CT+CC, OR = 1.23, 95% CI = 1.02–1.49). On subgroup analysis by ethnicity, similarly significant differences in T vs. C, TT vs. CC, and recessive model were found in Asians.

Conclusion

The present meta-analysis suggested that MTHFR C677T polymorphism were to substantially contribute to invasive cervical cancer in recessive model.     

Increased Risk of Developing Digestive Tract Cancer in Subjects Carrying the PLCE1 rs2274223 A>G Polymorphism: Evidence from a Meta-Analysis

Background

To date, the association between phospholipase C epsilon 1 (PLCE1) rs2274223 A>G and risk of digestive tract cancer (DTC) remains inconclusive. To derive a more precise estimation of the association, we conducted a meta-analysis on all eligible case–control studies involving 8281 cases and 10,532 controls.

Methods

A comprehensive search was conducted to identify all eligible studies of PLCE1 rs2274223 polymorphism and digestive tract cancer risk. The pooled odds ratio (OR) and the 95% confidence interval (95% CI) were calculated using a fixed or random effect model. Heterogeneity, publication bias, and sensitivity analysis were also explored.

Results

Overall, the PLCE1 rs2274223 A>G polymorphism was associated with risk of DTC in all genetic models (GA vs. AA: OR = 1.21, 95% CI = 1.14–1.29, P<0.001; GG vs. AA: OR = 1.30, 95% CI = 1.06–1.60, P = 0.012; GG/GA vs. AA: OR = 1.20, 95% CI = 1.10–1.32, P<0.001; GG vs. GA/AA: OR = 1.21, 95% CI = 1.01–1.46, P = 0.040). The recessive model did not reach statistically significance when the P values were Bonferroni corrected to 0.0125. In the stratified analysis by cancer type, ethnicity, and source of controls, significantly increased risk was observed for esophagus cancer, Asians in three genetic models (heterozygote comparison, homozygote comparison and dominant model), population-based studies in all genetic models, and for gastric cancer in the heterozygote comparison and dominant model after Bonferroni correction. However, in the subsite of gastric cancer, no significant association was found either in cardia or non-cardia gastric cancer.

Conclusion

Our study indicated that PLCE1 rs2274223 A>G polymorphism was significantly associated with increased risk of DTC, especially among Asian populations. Due to some minor limitations, our findings should be confirmed in further studies.     

Interleukin-10 ?592C/A, ?819C/T and ?1082A/G Polymorphisms with Risk of Type 2 Diabetes Mellitus: A HuGE Review and Meta-analysis

Background

Several studies have been conducted in recent years to evaluate the risk of type 2 diabetes mellitus (T2DM) and polymorphisms of interleukin (IL)-10. However, the results remain conflicting rather than conclusive. This meta-analysis aimed to summarize the current evidence from case-control studies that evaluated this association.

Methods

We carried out a search in Medline, EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) database for relevant studies. Data were extracted using a standardized form and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association.

Results

10 studies were included in our meta-analysis and systemic review. Our meta-analysis indicated that IL-10 −1082A/G polymorphism was associated with the risk of T2DM (GA vs. AA: OR = 1.21, 95% CI = 1.03–1.14; GA/GG vs. AA: OR = 1.22, 95% CI = 1.05–1.41), whereas there was no association between IL-10 −592C/A (CC/CA vs. AA: OR = 1.07, 95% CI = 0.59–1.93) or -819C/T (CC/CT vs. TT: OR = 0.93, 95% CI = 0.49–1.75) polymorphism and T2DM risk was found in our study.

Conclusions

This meta-analysis provides strong evidence that IL-10 −1082A/G polymorphism associated with risk of T2DM. However, no association of the IL-10 −592C/A or −819C/T polymorphism with T2DM risk was found. Additional well-designed large studies were required for the validation of our results.     

Association between the PARP1 Val762Ala Polymorphism and Cancer Risk: Evidence from 43 Studies

Background

Poly (ADP-ribose) polymerase-1 (PARP-1) plays critical roles in the detection and repair of damaged DNA, as well as cell proliferation and death. Numerous studies have examined the associations between PARP1 Val762Ala (rs1136410 T>C) polymorphism and cancer susceptibility; nevertheless, the findings from different research groups remain controversial.

Methods

We searched literatures from MEDLINE, EMBASE and CBM pertaining to such associations, and then calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using random-effects model. The false-positive report probability (FPRP) analysis was used to confirm the validity of significant findings. Moreover, potential effects of rs1136410 variants on PARP1 mRNA expression were analyzed for three ethnicities by combining data from HapMap (genotype) and SNPexp (mRNA expression).

Results

The final meta-analysis incorporated 43 studies, consisting of 17,351 cases and 22,401 controls. Overall, our results did not suggest significant associations between Ala variant (Ala/Ala or Ala/Val genotype) and cancer risk. However, further stratification analysis showed significantly increased risk for gastric cancer (Ala/Ala vs. Val/Val: OR = 1.56, 95% CI = 1.01–2.42, Ala/Val vs. Val/Val: OR = 1.34, 95% CI = 1.14–1.58, dominant model: OR = 1.41, 95% CI = 1.21–1.65 and Ala vs. Val: OR = 1.29, 95% CI = 1.07–1.55). On the contrary, decreased risk for brain tumor (Ala/Val vs. Val/Val: OR = 0.77, 95% CI = 0.68–0.87, dominant model: OR = 0.77, 95% CI = 0.68–0.87 and Ala vs. Val: OR = 0.82, 95% CI = 0.74–0.91). Additionally, we found that the Ala carriers had a significantly increased risk in all models for Asians. Our mRNA expression data provided further biological evidence to consolidate this finding.

Conclusions

Despite some limitations, this meta-analysis found evidence for an association between the PAPR1 Val762Ala and cancer susceptibility within gastric cancer, brain tumor and Asian subgroups.     

Association between the XRCC1 Polymorphisms and Thyroid Cancer Risk: A Meta-Analysis from Case-Control Studies

Background

The previous published data on the association between the X-ray repair cross-conplementation group 1 (XRCC1) polymorphisms and thyroid cancer risk remained controversial. Hence, we performed a meta-analysis on all available studies that provided 1729 cases and 3774 controls (from 11 studies) for XRCC1 Arg399Gln, 1040 cases and 2487 controls for Arg194Trp (from 7 studies), and 1432 cases and 3356 controls for Arg280His (from 8 studies).

Methodology/Principal Findings

PubMed, CNKI, and EMBASE database were searched to identify relevant studies. Overall, no significant association was found between XRCC1 Arg399Gln (recessive model: OR = 0.95, 95% CI = 0.77–1.15; dominant model: OR = 0.89, 95% CI = 0.75–1.05; homozygote model: OR = 0.92, 95% CI = 0.69–1.23; Heterozygote model: OR = 0.91, 95% CI = 0.80–1.03; additive model: OR = 0.93, 95% CI = 0.81–1.07), Arg194Trp (recessive model: OR = 1.41, 95% CI = 0.62–3.23; dominant model: OR = 1.01, 95% CI = 0.77–1.34; homozygote model: OR = 1.42, 95% CI = 0.55–3.67; Heterozygote model: OR = 1.03, 95% CI = 0.85–1.26; additive model: OR = 1.08, 95% CI = 0.81–1.42), and Arg280His (recessive model: OR = 1.08, 95% CI = 0.56–2.10; dominant model: OR = 1.01, 95% CI = 0.84–1.22; homozygote model: OR = 1.00, 95% CI = 0.51–1.96; Heterozygote model: OR = 1.04, 95% CI = 0.75–1.42; additive model: OR = 1.03, 95% CI = 0.86–1.23) and thyroid cancer risk when all the eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significant association was still not found in these three genetic polymorphisms.

Conclusions/Significance

In summary, this meta-analysis indicates that XRCC1 Arg399Gln, Arg280His, and Arg194Trp are not associated with thyroid cancer.     

Sulfotransferase SULT1A1 Arg213His Polymorphism with Cancer Risk: A Meta-Analysis of 53 Case-Control Studies

Background

The SULT1A1 Arg213His (rs9282861) polymorphism is reported to be associated with many kinds of cancer risk. However, the findings are conflicting. For better understanding this SNP site and cancer risk, we summarized available data and performed this meta-analysis.

Methods

Data were collected from the following electronic databases: PubMed, Web of Knowledge and CNKI. The association was assessed by odd ratio (OR) and the corresponding 95% confidence interval (95% CI).

Results

A total of 53 studies including 16733 cancer patients and 23334 controls based on the search criteria were analyzed. Overall, we found SULT1A1 Arg213His polymorphism can increase cancer risk under heterozygous (OR = 1.09, 95% CI = 1.01–1.18, P = 0.040), dominant (OR = 1.10, 95% CI = 1.01–1.19, P = 0.021) and allelic (OR = 1.08, 95% CI = 1.02–1.16, P = 0.015) models. In subgroup analyses, significant associations were observed in upper aero digestive tract (UADT) cancer (heterozygous model: OR = 1.62, 95% CI = 1.11–2.35, P = 0.012; dominant model: OR = 1.63, 95% CI = 1.13–2.35, P = 0.009; allelic model: OR = 1.52, 95% CI = 1.10–2.11, P = 0.012) and Indians (recessive model: OR = 1.93, 95% CI = 1.22–3.07, P = 0.005) subgroups. Hospital based study also showed marginally significant association. In the breast cancer subgroup, ethnicity and publication year revealed by meta-regression analysis and one study found by sensitivity analysis were the main sources of heterogeneity. The association between SULT1A1 Arg213His and breast cancer risk was not significant. No publication bias was detected.

Conclusions

The present meta-analysis suggests that SULT1A1 Arg213His polymorphism plays an important role in carcinogenesis, which may be a genetic factor affecting individual susceptibility to UADT cancer. SULT1A1 Arg213His didn''t show any association with breast cancer, but the possible risk in Asian population needs further investigation.     

Association between the XPG Asp1104His and XPF Arg415Gln Polymorphisms and Risk of Cancer: A Meta-Analysis

Backgroud

The XPG (xeroderma pigmentosum type G) Asp1104His and XPF (xeroderma pigmentosum type F) Arg415Gln polymorphisms had been implicated in cancer susceptibility. The previous published data on the association between XPG Asp1104His and XPF Arg415Gln polymorphisms and cancer risk remained controversial.

Methodology/Principal Findings

To derive a more precise estimation of the association between the XPG Asp1104His and XPF Arg415Gln polymorphisms and overall cancer risk, we performed a meta-analysis to investigate the association between cancer susceptibility and XPG Asp1104His (32,162 cases and 39,858 controls from 66 studies) and XPF Arg415Gln polymorphisms (17,864 cases and 20,578 controls from 32 studies) in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly elevated cancer risk was found when all studies were pooled into the meta-analysis of XPG Asp1104His (dominant model: OR = 1.05, 95% CI = 1.00–1.10; Asp/His vs. Asp/Asp: OR = 1.06, 95% CI = 1.01–1.11). In the further stratified and sensitivity analyses, significantly decreased lung cancer risk was found for XPF Arg415Gln (dominant model: OR = 0.82, 95% CI = 0.71–0.96; Arg/Gln versus Arg/Arg: OR = 0.83, 95% CI = 0.71–0.97; additive model: OR = 0.83, 95% CI = 0.72–0.95) and significantly increased other cancer risk was found among hospital-based studies for XPG Asp1104His (dominant model: OR = 1.23, 95% CI = 1.02–1.49).

Conclusions/Significance

In summary, this meta-analysis suggests that XPF Arg415Gln polymorphism may be associated with decreased lung cancer risk and XPG Asp1104His may be a low-penetrant risk factor in some cancers development. And larger scale primary studies are required to further evaluate the interaction of XPG Asp1104His and XPF Arg415Gln polymorphisms and cancer risk in specific populations.     

Association between CYP1A1 Ile462Val Variation and Acute Leukemia Risk: Meta-Analyses Including 2164 Cases and 4160 Controls

Background

Previously, CYP1A1 Ile462Val polymorphism has been indicated to be a risk factor for several malignancies. Increasing reports have focused on the association of CYP1A1 Ile462Val polymorphisms with susceptibility to acute leukemia and have generated controversial results. The goal of the present study was to derive a more precise estimation of the relationship.

Methods

Relevant literature has been rigorously searched and screened. Eligible studies were identified for the period up to Apr 2012. Meta-analyses evaluating the association of CYP1A1 Ile462Val variation with acute leukemia were carried out. Subgroup analyses on ethnicity, clinical types and source of controls were further performed.

Results

A total of thirteen publications including fourteen case-control studies with 2164 cases and 4160 controls were selected for analysis. The overall data indicated a significant association of CYP1A1 Ile462Val polymorphism with acute leukemia risk (Val/Val vs Ile/Ile OR = 1.49; 95% CI = 1.11–1.98; dominant model: OR = 1.26; 95% CI = 1.05–1.51; recessive model: OR = 1.38; 95% CI = 1.04–1.83). In subgroup analysis on ethnicity, increased risk was shown among mixed ethnicities (Val/Val vs Ile/Ile: OR = 2.36; 95% CI = 1.46–3.82; dominant model: OR = 1.37; 95% CI = 1.01–1.86; recessive model: OR = 2.20; 95% CI = 1.37–3.53) but not Asians or Caucasians. In subgroup analysis on clinical types, increased risk was observed in the acute lymphocytic leukemia (ALL) subgroup (Val/Val vs Ile/Ile: OR = 2.06; 95% CI = 1.42–3.01; recessive model: OR = 1.91; 95% CI = 1.32–2.76) but not in the acute myeloid leukemia (AML) subgroup.

Conclusion

The results of the present study suggest that CYP1A1 Ile462Val polymorphism might be a low-penetrant risk factor for acute leukemia. Subgroup analyses suggest that homozygous Val/Val alleles might modify the susceptibility to ALL.     

Relationship between Rad51 G135C and G172T Variants and the Susceptibility to Cancer: A Meta-Analysis Involving 54 Case-Control Studies

Background

The associations between Rad51 gene polymorphisms (G135C and G172T) and risk of cancer have been investigated, but the results were inconclusive. To get a comprehensive evaluation of the association above, we performed a meta-analysis of published studies.

Methods

A computerized search of PubMed, Embase and Web of Knowledge databases for all relevant studies was performed and the data were analyzed in a meta-analysis. The overall odds ratio (OR) with the 95% confidence interval (95% CI) was calculated to assess the strength of the association between Rad51 polymorphisms and cancer risk. Data were analyzed using fixed- or random-effects model when appropriate. Sensitivity analysis and publication bias test were also estimated.

Results

Overall, a total of 54 case-control studies were included in the current meta-analysis, among which 42 studies with 19,142 cases and 20,363 controls for RAD51 G135C polymorphism and 12 studies with 6,646 cases and 6,783 controls for G172T polymorphism. For G135C polymorphism, the pooled results indicated that significantly increased risk was found in overall cancers (homozygote model: OR = 1.776, 95% CI = 1.288–2.449; allelic genetic model: OR = 1.169, 95% CI = 1.016–1.345; recessive model: OR = 1.946, 95% CI = 1.336–2.835), especially in breast cancer (homozygote model: OR = 1.498, 95% CI = 1.026–2.189; recessive model: OR = 1.732, 95% CI  =  1.170–2.562). For G172T polymorphism, a decreased cancer risk was observed in head and neck cancer (homozygote model: OR  =  0.621, 95% CI  =  0.460–0.837; allelic genetic model: OR  =  0.824, 95% CI  =  0.716–0.948; recessive model: OR  =  0.639, 95% CI = 0.488–0.837).

Conclusions

Our results suggested that the Rad51 G135C polymorphism is a candidate for susceptibility to overall cancers, especially to breast cancer, and that the Rad51 G172T might play a protective role in the development of head and neck cancer.     

Antibody Prevalence and Factors Associated with Exposure to Orientia tsutsugamushi in Different Aboriginal Subgroups in West Malaysia

Background

Limited data is available on the current status of scrub typhus infection in the aboriginal population in Malaysia. This study was aimed to provide recent data on the degree of exposure of 280 individuals from seven aboriginal subgroups to Orientia tsutsugamushi (causative agent of scrub typhus) in West Malaysia. The environment, socioeconomic and behavioural risk factors associated with the disease were also investigated.

Methods/Findings

The antibody prevalence to O. tsutsugamushi ranged from 0 to 36.4% in seven subgroups, with high prevalence rates noted in subgroups involved in agricultural activity and the lowest prevalence rates noted in subgroups whose main occupations were associated to fishing. Univariate analysis indicated populations with age above 18 years (OR = 1.15, 95% CI = 1.02–1.30, P = 0.015), working (OR = 1.99, 95% CI = 1.01–3.92, P = 0.044), working at agriculture area (OR = 1.18, 95% CI = 0.98–1.42, P = 0.031), receiving household income less than US$ 166.7 (RM500) per month (OR = 2.43, 95% CI = 1.16–5.11, P = 0.016) and having close contact with animal pets (OR = 4.06, 95% CI = 1.20–13.76, P = 0.016) are significantly associated with exposure to O. tsutsugamushi. Multivariate analysis confirms that participants who are above 18 years old, receiving household income less than US$ 166.7 (RM500) per month and having close contact with animal pets are 3.6 times (95% CI = 1.81–7.03, P<0.001), 1.3 times (95% CI = 1.14–1.64, P = 0.002) and 1.2 times (95% CI = 1.05–1.06, P = 0.006) more likely to have exposure to O. tsutsugamushi, respectively.

Conclusion

The present study indicates that scrub typhus is still an important disease in the aboriginal population in Malaysia. Awareness about the disease and education on the preventive measures are important in reducing the risk of acquiring scrub typhus in the population studied.     

Poor Prognosis of Phosphatase of Regenerating Liver 3 Expression in Gastric Cancer: A Meta-Analysis

Background

Overexpression of phosphatase of regenerating liver 3 (PRL-3) has been implicated in gastric cancer (GC) metastasis. Epidemiological studies have evaluated the relationship between PRL-3 expression and prognosis in GC. However, results still remains controversial. In this study, a meta-analysis was performed to evaluate the association of PRL-3 expression with overall survival (OS) and clinicopathological characteristics.

Methods

Literature databases were searched to identify eligible studies dated until April 2013. Summary hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% CI) were calculated to estimate the association.

Results

A total of 1380 GC patients from six studies were included in the meta-analysis. Overall, the combined HR estimate for OS in a random-effect model was 1.89 (95% CI = 1.38–2.60; P<0.001). Results showed that PRL-3 overexpression was significantly associated with OS, indicating that it may be a biomarker for poor prognosis of GC. Both subgroup and sensitivity analyses further identified the prognostic role of PRL-3 expression in GC patients. Moreover, PRL-3 overexpression was significantly associated with tumor stage (OR = 2.25; 95% CI = 1.63–3.12; P<0.001), depth of invasion (OR = 2.03; 95% CI = 1.38–2.98; P<0.001), vascular invasion (OR = 2.52; 95% CI = 1.79–3.56; P<0.001), lymphatic invasion (OR = 3.74; 95% CI = 2.49–5.63; P<0.001), and lymph node metastasis (OR = 4.56; 95% CI = 2.37–8.76; P<0.001). However, when age, sex, tumor size, and tumor differentiation were considered, no obvious association was observed.

Conclusions

This meta-analysis reveals significant association of PRL-3 overexpression with OS and some clinicopathological features in GC. PRL-3 may be a predicative factor of poor prognosis and aggressive tumor behavior in GC patients.     

Association of Methylenetetrahydrofolate Dehydrogenase 1 Polymorphisms with Cancer: A Meta-Analysis

Background

Studies investigating the association between single-nucleotide polymorphisms (SNPs) of the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and cancer risk report conflicting results. To derive a more precise estimation of the relationship between MTHFD1 polymorphisms and cancer risk, the present meta-analysis was carried out.

Methodology/Principal Findings

A comprehensive search was conducted to determine all the eligible studies about MTHFD1 polymorphisms and cancer risk. Combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association between the MTHFD1 polymorphisms and cancer risk. We investigated by meta-analysis the effects of 2 polymorphisms in MTHFD1: G1958A (17 studies, 12348 cases, 44132 controls) and G401A (20 studies, 8446 cases, 14020 controls). The overall results indicated no major influence of these 2 polymorphisms on cancer risk. For G1958A, a decreased cancer risk was found in acute lymphoblastic leukemia (ALL)/Asians (the dominant: OR = 0.74, 95% CI = 0.58–0.94, P = 0.01; allelic: OR = 0.80, 95% CI = 0.65–0.99, P = 0.04) and other cancers (recessive: OR = 0.80, 95% CI = 0.66–0.96, P = 0.02). For G401A, the data showed that MTHFD1 G401A polymorphism was associated with a decreased colon cancer risk under dominant model (OR = 0.89, 95% CI = 0.80–0.99, P = 0.04).

Conclusions

The results suggest that MTHFD1 G1958A polymorphism might be associated with a decreased risk of ALL and other cancers. Meanwhile, the MTHFD1 G401A might play a protective role in the development of colon cancer. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.     

Genetic Associations with Diabetes: Meta-Analyses of 10 Candidate Polymorphisms

Aims

The goal of our study is to investigate the combined contribution of 10 genetic variants to diabetes susceptibility.

Methods

Bibliographic databases were searched from 1970 to Dec 2012 for studies that reported on genetic association study of diabetes. After a comprehensive filtering procedure, 10 candidate gene variants with informative genotype information were collected for the current meta-anlayses. Using the REVMAN software, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the combined contribution of the selected genetic variants to diabetes.

Results

A total of 37 articles among 37,033 cases and 54,716 controls were involved in the present meta-analyses of 10 genetic variants. Three variants were found to be significantly associated with type 1 diabetes (T1D): NLRP1 rs12150220 (OR = 0.71, 95% CI = 0.55–0.92, P = 0.01), IL2RA rs11594656 (OR = 0.86, 95% CI = 0.82–0.91, P<0.00001), and CLEC16A rs725613 (OR = 0.71, 95% CI = 0.55–0.92, P = 0.01). APOA5 −1131T/C polymorphism was shown to be significantly associated with of type 2 diabetes (T2D, OR = 1.27, 95% CI = 1.03–1.57, P = 0.03). No association with diabetes was showed in the meta-analyses of other six genetic variants, including SLC2A10 rs2335491, ATF6 rs2070150, KLF11 rs35927125, CASQ1 rs2275703, GNB3 C825T, and IL12B 1188A/C.

Conclusion

Our results demonstrated that IL2RA rs11594656 and CLEC16A rs725613 are protective factors of T1D, while NLRP1 rs12150220 and APOA5 −1131T/C are risky factors of T1D and T2D, respectively.     

The MDM2 309T>G Polymorphism and Ovarian Cancer Risk: A Meta-Analysis of 1534 Cases and 2211 Controls

Background

Recently, there have been a number of studies on the association between MDM2 (Murine Double Minute 2) 309 polymorphism and ovarian cancer risk. However, the results of previous reports remain controversial and ambiguous. Thus, we performed a meta-analysis to explore more precisely the association between MDM2 309 polymorphism and the risk of ovarian cancer.

Methods

A meta-analysis was performed to examine the association between MDM2 309T>G polymorphism and ovarian cancer risk. Odds ratio (OR) and its 95% confidence interval (CI) were used for statistical analysis.

Results

Our publication search identified a total of 6 studies with 1534 cases and 2211 controls. No significant association was found between MDM2 309T>G polymorphism and ovarian cancer risk in total population analysis. In the subgroup meta-analysis by ethnicity, a negative association was shown in Asian subgroup (G vs. T OR = 0.774, 95% CI = 0.628–0.955, P = 0.017, P _het = 0.327; GG vs. TT: OR = 0.601, 95% CI = 0.395–0.914, P = 0.017, P _het = 0.417; dominant model TG+GG vs. TT: OR = 0.661, 95% CI = 0.468–0.934, P = 0.019, P _het = 0.880), and no significant association in any genetic models among Caucasians was observed.

Conclusions

This meta-analysis provides evidence for the association between MDM2 309 polymorphism and ovarian cancer risk, supporting the hypothesis that MDM2 SNP309 G allele acts as an important ovarian cancer protective factor in Asians but not in Caucasians.