Association study of TRAF1/C5 polymorphism (rs10818488) with susceptibility to rheumatoid arthritis and systemic lupus erythematosus: A meta-analysis

To determine whether the tumor necrosis factor (TNF)-receptor associated factor 1/complement component 5 (TRAF1/C5) polymorphism (rs10818488) confers susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematous (SLE), a meta-analysis was performed. A total of 11 studies with 17 comparisons (11 for RA, 6 for SLE) were available for this meta-analysis, which consisted of 13,456 patients, 12,259 controls for RA and 1,894 patients, 6,729 controls for SLE. A significant association of the A allele of TRAF1/C5 polymorphism (rs10818488) with RA susceptibility was detected in the North Africa population (OR = 1.557, 95% CI: 1.225–1.977). Furthermore, the association between this allelic variant and SLE risk was additionally found in population of European (OR = 1.247, 95% CI: 1.060–1.466). Analysis also showed the A/G allelic frequency of TRAF1/C5 variant (rs10818488), in different healthy populations, had a different distribution (χ² = 269.41, P < 0.001). Taken together, our study demonstrates that the TRAF1/C5 polymorphism (rs10818488) may confer susceptibility to RA in North Africa population, and in European population, it might be a contributory factor towards SLE.     

Association of XRCC1 Arg399Gln polymorphism with bladder cancer susceptibility: A meta-analysis

Genetic variations in DNA repair genes are thought to modify DNA repair capacity and may to be related to cancer susceptibility. However, epidemiological study results have been inconsistent. In this meta-analysis, we assessed 24 case–control studies of association between the X-ray repair cross complementing group 1 (XRCC1) Arg399Gln polymorphism and bladder cancer susceptibility in the general population and in Asian and non-Asian subgroups. A moderately significant association with bladder cancer risk was found for AG vs GG (OR = 1.110, 95% CI = 1.018–1.210). No significant associations with bladder cancer risk were found for AA vs GG (OR = 0.942, 95% CI = 0.823–1.077), the dominant model AA/AG vs GG (OR = 1.075, 95% CI = 0.990–1.167) and the recessive model AA vs AG/GG(OR = 0.890, 95% CI = 0.788–1.005). In subgroup analysis, a moderately significant association was also found for AG vs GG (OR = 1.091, 95% CI = 1.008–1.180) in non-Asian subgroup. The analysis suggests that the XRCC1 Arg399Gln polymorphism might be a moderate risk factor for bladder cancer, especially in non-Asian population.     

XRCC1 polymorphisms and differentiated thyroid carcinoma risk: A meta-analysis

The objective of this study is to quantitatively derive a more precise estimation of the association between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms and differentiated thyroid carcinoma risk. A comprehensive literature search of three databases was conducted. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with fixed-effect models and random-effect models when appropriate. Overall, no association of the XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with differentiated thyroid carcinoma risk was found. In subgroup analyses, a decreased differentiated thyroid carcinoma risk was observed among Caucasians (Gln vs. Arg, OR = 0.86, 95% CI = 0.77–0.96, P = 0.343 for heterogeneity; Gln/Arg vs. Arg/Arg, OR = 0.84, 95% CI = 0.71–0.98, P = 0.229 for heterogeneity; Gln/Gln vs. Arg/Arg, OR = 0.77, 95% CI = 0.60–0.99, P = 0.477 for heterogeneity; dominant genetic model, OR = 0.82, 95% CI = 0.71–0.95, P = 0.272 for heterogeneity), not among Asians. No publication bias was observed. Our results suggest that XRCC1 Arg399Gln polymorphism is not associated with differentiated thyroid carcinoma risk, while a decreased risk is observed among Caucasian population.     

Analysis of DNA repair gene polymorphisms in glioblastoma

Background

Glioblastoma is the most common and aggressive primary brain tumor in adults. Despite several factors such as ionizing radiation exposure or rare genetic syndromes have been associated with the development of glioblastoma, no underlying cause has been identified for the majority of cases. We thus aimed to investigate the role of DNA repair polymorphisms in modulating glioblastoma risk.

Methods

Genotypic and allelic frequencies of seven common polymorphisms in DNA repair genes involved in nucleotide excision repair (ERCC1 rs11615, ERCC2 rs13181, ERCC6 rs4253079), base excision repair (APEX1 rs1130409, XRCC1 rs25487), double-strand break repair (XRCC3 rs861539) and mismatch repair (MLH1 rs1800734) pathways were analyzed in 115 glioblastoma patients and 200 healthy controls. Haplotype analysis was also performed for ERCC1 rs11615 and ERCC2 rs13181 polymorphisms, located on the same chromosomal region (19q13.32).

Results

Our results indicated that carriers of the ERCC2 Gln/Gln genotype were associated with a lower glioblastoma risk (OR = 0.32, 95% CI 0.12–0.89; P = 0.028), whereas carriers of the MLH1 AA genotype were associated with an increased risk of glioblastoma (OR = 3.14, 95% CI 1.09–9.06; P = 0.034). Furthermore, the haplotype containing the C allele of ERCC2 rs13181 polymorphism and the T allele of ERCC1 rs11615 polymorphism was significantly associated with a protective effect of developing glioblastoma (OR = 0.34, 95% CI 0.16–0.71; P = 0.004).

Conclusions

These results pointed out that MLH1 rs1800734 and ERCC2 rs13181 polymorphisms might constitute glioblastoma susceptibility factors, and also suggested that the chromosomal region 19q could be important in glioblastoma pathogenesis.     

Association between the XRCC3 T241M polymorphism and risk of cancer: Evidence from 157 case–control studies

The T241M polymorphism in the X-ray cross-complementing group 3 (XRCC3) had been implicated in cancer susceptibility. The previous published data on the association between XRCC3 T241M polymorphism and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and XRCC3 T241M (61,861 cases and 84,584 controls from 157 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ration [OR] = 1.07, 95% confidence interval [CI] = 1.00–1.13; recessive model: OR = 1.15, 95% CI = 1.08–1.23; additive model: OR = 1.17, 95% CI = 1.08–1.28) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of bladder cancer and breast cancer, especially in Caucasians. In addition, significantly decreased lung cancer risk was also observed. In summary, this meta-analysis suggests the participation of XRCC3 T241M in the susceptibility for bladder cancer and breast cancer, especially in Caucasians, and XRCC3 T241M polymorphism is associated with decreased lung cancer risk. Moreover, our work also points out the importance of new studies for T241M association in some cancer types, such as gastric cancer, colorectal cancer, and melanoma skin cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC3 polymorphism in cancer development.     

The effect of chemokine receptor gene polymorphisms (CCR2V64I,CCR5-59029G>A and CCR5Δ32) on renal allograft survival in Pakistani transplant patients

Background

Gene polymorphisms of the chemokine receptors CCR2 and CCR5 (CCR2V64I, CCR5-59029G>A and CCR5Δ32) have been shown to be associated with renal allograft rejection. The aim of this study was to investigate the association of these polymorphisms with allograft rejection among Pakistani transplant patients.

Method

A total of 606 renal transplant patients and an equal number of their donors were included in this study. DNA samples were used to amplify polymorphic regions of CCR2V64I, CCR5-59029G>A and CCR5Δ32 by polymerase chain reaction using sequence specific primers. The amplified products of CCRV64I and CCR5-59029G>A were digested with restriction enzymes (BsaB1 and Bsp12861) respectively. The CCR5Δ32 genotypes were determined by sizing the PCR amplicons. The association of these polymorphisms with the biopsy proven rejection and other clinical parameters was evaluated using the statistical software SPSS v.17.

Results

In this study, the G/G genotype of CCR2V64I was associated with a high frequency of allograft rejection (p = 0.009; OR = 2.14; 95% CI = 1.2–3.7). Rejection episode(s) in the GA + AA genotypes were found to be significantly lower as compared to the GG genotype (p = 0.009; OR = 0.4; 95% CI = 0.2–0.8). The Kaplan–Meier curve also indicated a reduced overall allograft survival for patients with the G/G genotype of CCR2V64I (59.2 ± 1.4 weeks, log p = 0.008). There was a significant association with rejection by female donors possessing the CCR2 GG genotype (p = 0.02; OR = 2.6; CI = 1.1–6.3) and male donors with the CCR5-59029 GG genotype (p = 0.004; OR = 1.7; CI = 1.03–3.01).

Conclusion

This study shows an association of the CCR2V64I (G/G) genotype with renal allograft rejection. However, no such association was found for the CCR5 gene polymorphisms. Therapeutic interventions such as blocking the CCR2 receptor (especially G polymorphism) may yield better survival of renal allograft in this patient group. Further, chemokine receptors may be added to the spectrum of the immunogenetic factors that are known to be associated with renal allograft rejection.     

The CXCL12 G801A polymorphism and cancer risk: Evidence from 17 case‐control studies

CXCL12 has been implicated in human carcinogenesis, but the association between the most-studied G801A polymorphism (rs1801157) and the risk of various cancers was reported with inconclusive results. The aim of this study was to assess the association between the CXCL12 G801A polymorphism and cancer risk. A meta-analysis of 17 studies with 3048 cancer patients and 4522 controls was conducted to evaluate the strength of the association using odds ratio (OR) with its 95% confidence interval (CI). The overall results showed that the variant genotypes were associated with a significantly increased risk of all cancer types (OR = 1.38, 95%CI = 1.18–1.61 for GA versus GG, and OR = 1.36, 95%CI = 1.17–1.59 for GA/AA versus GG). In the stratified analyses, there was a significantly increased risk for the studies of breast cancer (OR = 1.64, 95% CI = 1.16–2.33 for AA versus GG, OR = 1.42, 95%CI = 1.18–1.71 for GA versus GG, and OR = 1.44, 95%CI = 1.21–1.72 for GA/AA versus GG) and lung cancer (OR = 2.86, 95% CI = 1.75–4.69 for AA versus GG, OR = 1.62, 95% CI = 1.20–2.18 for GA vs. GG, OR = 1.80, 95% CI = 1.36–2.39 for GA/AA versus GG, and OR = 2.24, 95%CI = 1.41–3.57 for AA versus GA/GG), which remained for the studies of Asian populations and hospital-based control sources. Although some modest bias could not be eliminated, this meta-analysis indicates that the CXCL12 G801A polymorphism is a low-penetrance risk factor for cancer development.     

Association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo

Background

Some studies suggested that Glutathione S-transferases M1/T1(GSTM1/T1) null polymorphisms may be associated with the risk of vitiligo.

Aims

The purpose of this study is to further evaluate the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo.

Methods

We carried out a retrieval of studies in the databases. Odds ratios (OR) and 95% confidence intervals (95% CIs) were used to assess the strength of this association. We analyzed the data using Stata 11.0.

Results

Six case–control studies including 1358 cases and 1673 controls were included in this meta-analysis. Our overall results showed the GSTM1 or GSTT1 null polymorphism was associated with vitiligo (GSTM1:OR = 1.59, 95% CI: 1.21–2.08, P = 0.001; GSTT1: OR = 1.30, 95% CI: 1.12–1.51, P = 0.001). In the subgroup analysis, the GSTM1 null polymorphism might be a genetic risk factor to vitiligo in East Asian (OR = 1.71, 95% CI: 1.12–2.63, P = 0.014) but not in the Mediterranean, however individuals with the GSTT1 null polymorphism in the Mediterranean (OR = 1.76, 95% CI: 1.15–2.71, P = 0.010) but not in East Asian have a greater predisposition to vitiligo. In addition there was also a significant trend toward an association with the combination of the GSTM1 null and GSTT1 null in either East Asians or Mediterraneans.

Conclusion

The GSTM1/T1 null polymorphisms may be associated with vitiligo. More studies are needed to confirm this conclusion.     

LIG4 and RAD52 DNA repair genes polymorphisms and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with a strong genetic background. Nevertheless, SLE might also be triggered due to environmental factors, such as UV light exposure. DNA double strand breaks (DSBs) may be induced secondarily by UV radiation, increasing DNA immunogenicity and in SLE patients DNA repair is diminished, allowing the accumulation of DSBs and genomic instability. LIG4 and RAD52 genes play important roles in DNA repair mechanisms and a recent microarray analysis showed their differential expression in active SLE patients. In this study we investigated a potential association between LIG4 and RAD52 single nucleotide polymorphisms (SNPs) and SLE predisposition in a Southeast Brazilian population. We assessed four Tag SNPs in LIG4 and three in RAD52 gene region, encompassing most of the gene sequence, in 158 SLE patients and 212 healthy controls. We also performed SNPs analysis considering clinical manifestation, gender and ethnicity in SLE patients. Our data did not show association between LIG4 and RAD52 SNPs and SLE, its clinical manifestations or ethnicity in the tested population. The analysis regarding ethnicity and SLE clinical manifestations indicated Caucasian-derived patients as more susceptible to cutaneous and hematological alterations than the African-derived. To our knowledge, this is the first association study involving LIG4 and RAD52 genes and SLE predisposition.     

The arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene SG13S114 polymorphism and ischemic stroke in Chinese population: A meta-analysis

Previous studies have indicated that the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene SG13S114 polymorphism is associated with risk of ischemic stroke (IS), but the results remain inconclusive even in Chinese population. A meta-analysis of 10 case-control studies was conducted on the relationship between ALOX5AP SG13S114 polymorphism and susceptibility to IS in Chinese population published domestically and abroad from September 2007 to December 2012. Data were extracted by two authors and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Meta-analysis results showed that the significant association between SG13S114 variant and IS was found under the allelic (OR = 0.87, 95% CI: 0.80–0.96, P = 0.004), dominant (OR = 0.75, 95% CI: 0.62–0.92, P = 0.005), and recessive (OR = 0.89, 95% CI: 0.82–0.97, P = 0.005) genetic models in Chinese population. In subgroup meta-analysis, SG13S114 variant and atherothrombotic stroke, rather than lacunar stroke, showed the significant association under the allelic (OR = 0.86, 95% CI: 0.80–0.92, P < 0.0001), dominant (OR = 0.72, 95% CI: 0.57–0.91, P = 0.006), and recessive (OR = 0.86, 95% CI: 0.78–0.95, P = 0.002) models. ALOX5AP SG13S114 polymorphism is associated with susceptibility to IS in Chinese population.     

Association of ANRIL polymorphism (rs1333049:C>G) with myocardial infarction and its pharmacogenomic role in hypercholesterolemia

Single nucleotide polymorphisms (SNPs) of non-coding RNA in the INK4 locus (ANRIL) have been found to be associated with myocardial infarction (MI). However, the effect of rs1333049:C>G in INK4 locus in familial hypercholesterolemia patients and on lipid profile of the patients has not been studied in Pakistan. We therefore investigated the association of SNP rs1333049:C>G with MI as well as familial hypercholesterolemia patients and also determined the effect of genotype on lipid levels in a northern Pakistani population. A case–control association study was performed in which 611 individuals (294 patients, 290 healthy controls and 27 patients from hypercholesterolemia families) were genotyped for rs1333049:C>G, using an Allele specific polymerase chain reaction. We found a significant association of rs1333049:C>G with MI (χ² = 22.3, p < 0.001). The frequency of risk genotype CC was significantly different from the healthy controls (p < 0.001, χ² = 22.3). The risk allele C was at a higher frequency in the MI patients as compared to the controls (odds ratio [OR] = 1.55 (95% confidence interval [CI] = 1.22–1.96), p < 0.001). The logistic regression analysis for the genotype distribution resulted in strong association of risk allele C with MI under recessive model (OR = 3.17 (95% CI = 1.85–5.44) p < 0.001). When the data were further analyzed along the lines of gender, a significant association with both males and females was observed.     

Association of two ERCC4 tagSNPs with susceptibility to atrophic gastritis and gastric cancer in Chinese

Genetic polymorphisms in excision repair cross-complementing group 4 (ERCC4) may contribute to the risk of cancer development. However, there are few reports regarding to susceptibility to gastric cancer (GC) or its precursor, atrophic gastritis (AG). Thereby, we investigated the association between two tag single nucleotide polymorphisms (tagSNPs) rs6498486 and rs254942, which represents the majority of common SNPs of ERCC4 gene, and the risks of GC and AG development in a sex- and age-matched case–control designed study. We found that rs6498486 polymorphism was associated with a reduced AG risk in total population (for AC vs. AA: OR = 0.69, 95%CI = 0.52–0.94, P = 0.016; for AC/CC vs. AA: OR = 0.68, 95%CI = 0.51–0.92, P = 0.010) as well as in the subpopulation of youngers (age < 60 years) (for AC/CC vs. AA: OR = 0.67, 95%CI = 0.45–0.99, P = 0.048). For the rs254942 polymorphism, compared with the common TT genotype, the genotypes of CT and CT/CC were only observed to reduce AG risk in the subgroups of males (for CT vs. TT: OR = 0.64, 95%CI = 0.45–0.90, P = 0.012; for CT/CC vs. TT: OR = 0.66, 95%CI = 0.47–0.92, P = 0.016) and youngers (for CT vs. TT: OR = 0.72, 95%CI = 0.53–0.97, P = 0.035; for CT/CC vs. TT: OR = 0.74, 95%CI = 0.55–0.99, P = 0.045). However, no significant statistical association of the two SNPs with GC susceptibility was observed in the total population. Only rs6498486 AC and AC/CC genotypes were found to be marginally associated with a reduced GC risk in the subgroup of males (for AC vs. AA: OR = 0.69, 95%CI = 0.49–0.99, P = 0.043; for AC/CC vs. AA: OR = 0.71, 95%CI = 0.50–0.99, P = 0.046). Our findings suggested that the ERCC4 rs6498486 and rs254942 may be associated with AG risk. Further validation of our results in larger populations and additional studies evaluating their molecular function are required.     

Polymorphism T→C of gene CYP17 promoter and polycystic ovary syndrome risk: a meta-analysis

The T → C polymorphism of CYP17 gene has been inconsistently associated with polycystic ovary syndrome (PCOS) risk. We examined the association by performing a meta-analysis. Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP17 polymorphism and PCOS were calculated in a fixed-effects model and a random-effects model when appropriate. The pooled ORs were performed for co-dominant model (CC vs. TT, TC vs. TT), dominant model (CC + TC vs. TT), and recessive model (CC vs. TC + TT). Subgroup analyses were performed by ethnicity, country, Hardy-Weinberg equilibrium (HWE) in controls and study sample size. This meta-analysis included 10 case-control studies, which included 1321 PCOS cases and 1017 controls. Overall, the variant genotypes (CC and TC) were not associated with PCOS risk, compared with the wild-type TT homozygote. Similarly, no associations were found in the dominant and recessive models. Stratified analyses by ethnicity/country also detected no significant association. However, limiting the analysis to the studies within HWE, a significantly increased risk was observed (TC vs. TT, OR = 1.44, 95% CI = 1.10-1.88; dominant model, OR = 1.41, 95% CI = 1.10-1.81). Moreover, when stratifying by study sample size, a significantly elevated risk was found among small sample studies (≤ 200 subjects), but not among large sample studies (> 200 subjects). This meta-analysis suggests that the CYP17 T/C polymorphism may be not associated with PCOS risk, while the observed increase in risk of PCOS may be due to small-study bias.     

The polymorphism − 1131T > C in apolipoprotein A5 gene is associated with dyslipidemia in Brazilian subjects

Background

Polymorphisms in apolipoprotein A5 gene (APOA5) have been associated with higher triglyceride levels in many populations. The aim of the study was to determine the allelic and genotypic distribution of the APOA5 − 1131T > C polymorphism and to identify the association of the genetic variant and the risk for dyslipidemia.

Methods

We genotyped 109 dyslipidemic subjects and 107 controls. The total cholesterol, triglycerides and HDL-c were determined enzymatically. Comparison of means among groups was calculated by ANOVA. Significant differences among groups were evaluated by Student–Newman–Keuls test.

Results

The minor allele C was more frequent in dyslipidemic subjects than controls (p = 0.019) and confers an increased individual risk for dyslipidemia (OR = 1.726, CI 95% = 1.095–2.721). The genotype analysis by gender showed that this allele was more frequent in dyslipidemic males (p = 0.037; OR = 2.050, CI 95% = 1.042–4.023). When participants were analyzed according to genotypes TT and TC/CC, C-carriers presented higher cholesterol and triglycerides levels than TT homozygous (p = 0.046 and 0.049, respectively).

Conclusions

The allele C confers higher total cholesterol and triglycerides levels in dyslipidemic adults. The APOA5 − 1131T > C polymorphism is associated with dyslipidemia in male subjects.     

Poly (AT) deletion/insertion polymorphism of the XPC gene contributes to urinary system cancer susceptibility: A meta-analysis

Numerous studies have investigated the association between xeroderma pigmentosum complementation group C (XPC) poly (AT) deletion/insertion (PAT −/+) polymorphism and cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 32 publications including 10,214 cases and 11,302 controls to acquire a more robust estimation of the relationship. We searched publications from MEDLINE, EMBASE and CBM which assessed the associations between XPC PAT −/+ polymorphism and cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We found that individuals carrying the PAT +/+ genotype have significantly increased cancer risk (PAT +/+ vs. PAT −/−: OR = 1.18, 95% CI = 1.03–1.35 and recessive model: OR = 1.19, 95% CI = 1.06–1.33). Further stratification analysis showed a significantly increased risk for prostate cancer (PAT +/+ vs. PAT −/−: OR = 2.20, 95% CI = 1.39–3.48, recessive model: OR = 2.07, 95% CI = 1.33–3.23 and PAT + vs. PAT −: OR = 1.39, 95% CI = 1.12–1.71), bladder cancer (recessive model: OR = 1.33, 95% CI = 1.03–1.72), Caucasian ethnicity (recessive model: OR = 1.21, 95% CI = 1.02–1.43), population-based studies (recessive model: OR = 1.23, 95% CI = 1.05–1.43) and studies with relatively large sample size (PAT +/+ vs. PAT −/−: OR = 1.18, 95% CI = 1.04–1.35 and recessive model: OR = 1.20, 95% CI = 1.08–1.33). Despite some limitations, this meta-analysis established solid statistical evidence for the association between the XPC PAT +/+ genotype and cancer risk, especially for urinary system cancer, but this association warrants further validation in single large studies.     

The effect of XPD/ERCC2 Lys751Gln polymorphism on acute leukemia risk: A systematic review and meta-analysis

Aims

Epidemiological studies have assessed the association between xeroderma pigmentosum group D (XPD) Lys751Gln and acute leukemia risk with conflicting results. We performed this meta-analysis to derive a more precise estimation of the relationship. Pooled odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the strength of the association.

Results

Ten published case–control studies including a total of 1494 cases and 2259 controls were identified. Overall, significant risk effects of Lys751Gln genotype was found under the dominant model (OR = 1.16; 95% CI = 1.01–1.34; P = 0.032). When stratified by clinical types, the variant genotype was associated with the acute myeloid leukemia (AML) risk under the heterozygote comparison (OR = 1.20; 95% CI = 1.00–1.43; P = 0.048), the homozygote comparison (OR = 1.35; 95% CI = 1.05–1.74; P = 0.019) and the dominant model (OR = 1.23; 95% CI = 1.04–1.45; P = 0.015), respectively. Furthermore, significantly increased risks were also pronounced in Caucasian AML patients (the homozygote comparison: OR = 1.38; 95% CI = 1.07–1.78; P = 0.013; the dominant model: OR = 1.23; 95% CI = 1.03–1.46; P = 0.020; and the recessive model: OR = 1.26; 95% CI = 1.00–1.60; P = 0.050). No evident heterogeneities were observed for the overall data under all genetic models. In addition, no statistical evidence for publication bias was found using the method of Begg's and Egger's tests.

Conclusion

This meta-analysis suggested that XPD Lys751Gln polymorphism might be a risk factor for AML and Caucasian acute leukemia patients.     

Effects of polymorphisms in nucleotide excision repair genes on glioma risk in a Chinese population

We performed a case-control study to assess the relationship between six single nucleotide polymorphisms (SNPs) of xeroderma pigmentosum complementation group F (XPF) on glioma risk in a Chinese population. The six SNPs were genotyped in 330 glioma cases and 652 cancer-free controls using a 384-well plate format on the Sequenom MassARRAY platform (Sequenom, San Diego, USA). Rs1800067 did not follow the Hardy–Weinberg equilibrium in the control group, and the genotype distributions differed significantly between the two groups for SNPs rs1800067 and rs2276466. For rs1800067, the variant genotype T/T was strongly associated with an increased risk of glioma when compared with the A/A genotype (OR = 3.77, 95% CI = 2.38–6.01). Individuals with the rs1800067 G allele had a relatively high risk of glioma in a dominant model (OR = 3.47, 95% CI = 2.26–5.37). The rs2276466 G/G genotype was significantly associated with a moderate increased risk of glioma (OR = 1.82, 95% CI = 1.10–3.02) in a codominant model, and variation of rs25489 was associated with a 1.31- and 1.78-fold glioma risk in dominant and recessive models, respectively. Our study is the first to identify polymorphisms in rs1800067 and rs2276466 as correlated with glioma susceptibility.     

Does cytochrome P450 1A1 MspI polymorphism increase acute lymphoblastic leukemia risk? Evidence from 2013 cases and 2903 controls

Previous studies indicated that cytochrome P450 1A1 (CYP1A1) MspI polymorphism might be a possible risk factor for several malignancies. Increasing investigations have been conducted on the association of CYP1A1 MspI polymorphisms with acute lymphoblastic leukemia (ALL). However, the results were controversial. The goal of the present study was to address this controversy by pooling and analyzing the published data. Therefore, quantitative meta-analyses evaluating the association of CYP1A1 MspI variation with ALL were performed and subgroup analyses on ethnicity, age groups and source of controls were further carried out. After a rigorous search in the Medline, EMBASE, OVID, ScienceDirect, and CNKI databases, all eligible studies for the period up to May 2012 were identified and screened according to the inclusion and exclusion criteria. Consequently, a total of fourteen case–control studies including 2013 cases and 2903 controls were selected for analysis. The overall data indicated a significant association of CYP1A1 MspI polymorphism with ALL risk (CC + TC vs TT: OR = 1.33; 95%CI = 1.05–1.69). In a subgroup analysis according to ethnicity, no associations were shown among Asians, Caucasians and Mixed ethnicity subgroups. In the subgroup analysis regarding age groups, increased risk was observed in the childhood ALL subgroup (C vs T: OR = 1.23; 95%CI = 1.04–1.45; CC + TC vs TT: OR = 1.31; 95%CI = 1.08–1.59). In the subgroup analysis stratified by source of controls, significant associations were observed in the population-based subgroup (CC + TC vs TT: OR = 1.33; 95%CI = 1.03–1.71). In conclusion, the results of the present study suggest that CYP1A1 MspI polymorphism might be a risk factor for ALL, particularly childhood ALL. Future well-designed high quality investigations with large sample sizes are required to elucidate the gene polymorphism–ALL relationship and gene–environment interactions.