Association of CDKN1B gene polymorphisms with susceptibility to breast cancer: a meta-analysis

A number of case–control studies have been conducted to investigate the association of CDKN1B gene polymorphisms with breast cancer. However, these studies reported conflicting results. The aim of our study was to quantitatively summarize the association of CDKN1B gene polymorphisms with breast cancer. Systemic searches of the PubMed, Excerpta Medica Database, and Chinese Biomedical Literature Database databases were performed, with the last report up to Oct 2012. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of the association. Seven studies including 6,822 cases and 7,186 controls were involved in this meta-analysis, which was performed for two CDKN1B gene polymorphisms (rs2066827 and rs34330). Significant association was found for rs34330 polymorphism (T versus C: OR = 1.10, 95 % CI = 1.03–1.18, P = 0.003; CT + TT versus CC: OR = 1.38, 95 % CI = 0.98–1.93, P = 0.07; TT versus CC + CT: OR = 1.06, 95 % CI = 0.93–1.21, P = 0.38; TT versus CC: OR = 1.23, 95 % CI = 1.04–1.45, P = 0.02; CT versus CC: OR = 1.42, 95 % CI = 0.97–2.09, P = 0.07), but not for rs2066827 polymorphism (G versus T: OR = 0.99, 95 % CI = 0.91–1.08, P = 0.84; TG + GG versus TT: OR = 0.98, 95 % CI = 0.89–1.08, P = 0.69; GG versus TT + TG: OR = 1.04, 95 % CI = 0.83–1.30, P = 0.75; GG versus TT: OR = 1.03, 95 % CI = 0.82–1.30, P = 0.77; TG versus TT: OR = 0.97, 95 % CI = 0.88–1.08, P = 0.58). This meta-analysis suggests that breast cancer may be associated with CDKN1B gene rs34330 polymorphism, but not rs2066827 polymorphism.     

Association between the CYP1A2-164 A/C polymorphism and colorectal cancer susceptibility: a meta-analysis

To date, epidemiological studies have assessed the association between CYP1A2-164 A/C polymorphism and colorectal cancer susceptibility. However, the results of these studies remained controversial. We aimed to examine the associations by conducting a meta-analysis of case–control studies. A total of 11 studies including 5,093 cases and 5,941 controls evaluated the association between the CYP1A2-164 A/C polymorphism and colorectal cancer susceptibility. No significantly associations were found in all genetic models (CC vs. AA: OR = 1.14, 95 % CI = 0.93–1.40; AC vs. AA: OR = 1.05, 95 % CI = 0.91–1.20; dominant model: OR = 1.08, 95 % CI = 0.95–1.24; recessive model: OR = 1.10, 95 % CI = 0.95–1.28). In the subgroup analysis by ethnicity or source of controls, there were still no significant associations detected in all genetic models. This meta-analysis suggested the CYP1A2-164 A/C polymorphism was not a risk factor for increasing colorectal cancer, further large and well-designed studies are needed to confirm these conclusions.     

Pre-mir-27a rs895819 polymorphism and cancer risk: a meta-analysis

Aberrant expression of miRNAs plays critical roles in cancer development. Single nucleotide polymorphism (SNP) in miRNA precursors may affect miRNA expression levels. An important SNP in the pre-mir-27a with a A to G change (rs895819) was identified. Several original studies have explored the role of this SNP in cancer risk, but the results of these studies remain conflicting rather than conclusive. Therefore, we performed a meta-analysis of the published studies to derive a more precise estimation of the association between pre-mir-27a rs895819 polymorphism and cancer risk. In this meta-analysis, a total of 6 case–control studies (including 3,255 cases and 4,181 controls) were analyzed. The results of the overall meta-analysis did not suggest any associations between pre-mir-27a rs895819 polymorphism and cancer susceptibility. However, an decreased risk was observed in the subgroup of breast cancer patients (G vs A: OR = 0.90, 95 % CI = 0.83 ~ 0.97; P _{heterogeneity}  = 0.75) or in the subgroup of Caucasian race (G vs A: OR = 0.90, 95 % CI = 0.83 ~ 0.97, P _{heterogeneity}  = 0.78, I ² = 0; AG vs AA: OR = 0.84, 95 % CI = 0.75 ~ 0.94, P _{heterogeneity}  = 0.35, I ² = 3.7 %; GG+AG vs AA: OR = 0.85, 95 % CI = 0.76 ~ 0.94, P _{heterogeneity}  = 0.48, I ² = 0). The findings suggest that pre-mir-27a rs895819 polymorphism may have some relation to breast cancer susceptibility or cancer development in Caucasian.     

The association between common genetic variant of microRNA-499 and cancer susceptibility: a meta-analysis

Published data on the association between microRNA-499 (miR-499) rs3746444 T>C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of this relationship, a comprehensive meta-analysis was performed on nine published studies, with a total sample of 4,794 cases and 5,971 controls. Overall, no significant association was found between miR-499 polymorphism and cancer risk after all studies were pooled into the meta-analysis. However, in the subgroup analysis by ethnicity, significant association with an increased risk was found in Asian (CC vs. TT: OR = 1.439, 95 % CI = 1.118–1.852, P = 0.005, p-heterogeneity = 0.116). Moreover, in the the subgroup analysis by cancer type, this SNP was associated with an increased risk of breast cancer in the recessive model (OR = 1.077, 95 % CI = 1.008–1.151, P = 0.028, p-heterogeneity = 0.125). Our findings support the view that miR-499 rs3746444 T>C polymorphism is associated with breast cancer and the C allele can increase cancer susceptibility in Asian.     

Meta-analysis on the association of nucleotide excision repair gene XPD A751C variant and cancer susceptibility among Indian population

Polymorphism A751C (A>C) in XPD gene has shown susceptibility to many cancers in Indian population; however the results of these studies are inconclusive. Thus, we performed this meta-analysis to estimate the association between XPD A751C polymorphism and overall cancer susceptibility. We quantitavely synthesized all published studies of the association between XPD A751C polymorphism and cancer risk. Pooled odds ratios (ORs) and 95 % CI were estimated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model. A total of thirteen studies including 3,599 controls and 3,087 cancer cases were identified and analyzed. Overall significant results were observed for C allele carrier (C vs. A: p = 0.001; OR 1.372, 95 % CI 1.172–1.605) variant homozygous (CC vs. AA: p = 0.001; OR 1.691, 95 % CI 1.280–2.233) and heterozygous (AC vs. AA: p = 0.001; OR 1.453, 95 % CI 1.215–1.737) genotypes. Similarly dominant (CC+AC vs. AA: p = 0.001; OR 1.512, 95 % CI 1.244–1.839) and recessive (CC vs. AA+AC: p = 0.001; OR 1.429, 95 % CI 1.151–1.774) genetic models also demonstrated risk of developing cancer. This meta-analysis suggested that XPD A751C polymorphism likely contribute to cancer susceptibility in Indian population. Further studies about gene–gene and gene–environment interactions are required.     

XRCC1 Arg399Gln polymorphism contributes to increased risk of colorectal cancer in Chinese population

Previous studies investigating the association between X-ray repair cross-complementation group 1 (XRCC1) Arg399Gln polymorphism and colorectal cancer risk in Chinese provided inconsistent findings. To assess the association in Chinese population, a meta-analysis was performed. Eligible studies were searched in Pubmed, Emabse, and China National Knowledge Infrastructure databases. Odds ratios (OR) with the corresponding 95 % confidence intervals (95 %CI) were pooled to assess the association. Seven case–control studies involving a total of 2136 colorectal cancer cases and 3168 controls were finally included in the meta-analysis. Our analysis suggested that the variant genotypes of XRCC1 Arg399Gln were associated with an increased risk of colorectal cancer in Chinese population (Gln vs. Arg: random effect model OR = 1.24, 95 %CI = 1.01–1.52, P = 0.041; GlnGln vs. ArgArg: random effect model OR = 1.52, 95 %CI = 1.07–2.15, P = 0.019; and Recessive model: fixed effect model OR = 1.37, 95 %CI = 1.12–1.67, P = 0.002). There was low risk of publication bias in present meta-analysis. Our meta-analysis provides an evidence for the association between XRCC1 Arg399Gln polymorphism and colorectal cancer risk in Chinese population, and XRCC1 Arg399Gln variant genotypes contribute to increased risk of colorectal cancer in Chinese.     

Associations between interferon regulatory factor 5 polymorphisms and rheumatoid arthritis: a meta-analysis

The aim of this study was to determine whether interferon regulatory factor 5 (IRF5) polymorphisms confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. We searched the literature using the Pubmed and Embase databases and conducted meta-analyses on associations between the four IRF5 polymorphisms (rs2004640, rs729302, rs752637, and rs2280714) and RA susceptibility, using fixed and random effects models. A total of 12 comparison studies were considered in this meta-analysis, which in total involved 7,916 RA patients and 6,452 controls, and eight European, three Asian, and one Argentinean population. Meta-analysis showed an association between the minor allele of rs2004640 and RA in all subjects (odds ratio [OR] = 0.928, 95 % confidence interval [CI] = 0.865–0.996, P = 0.037). After stratification by ethnicity, analysis indicated that the minor allele was significantly associated with RA in Europeans (OR = 0.889, 95 % CI = 0.839–0.941, P = 5.03 × 10^?6), but not in Asians (OR = 1.057, 95 % CI = 0.978–1.144, P = 0.164). A direct comparison between anti-citrullinated peptide antibody-positive and -negative patients revealed no difference of the frequency of the rs2004640 minor allele (OR = 1.047, 95 % CI = 0.813–1.348, P = 0.724). Meta-analysis identified a significant association between RA and the minor allele of the rs729302 polymorphism in the overall population (OR = 0.896, 95 % CI = 0.826–0.972, P = 0.009) and in Asians (OR = 0.862, 95 % CI = 0.795–0.935, P = 3.50 × 10^?5), but not in Europeans (OR = 0.951, 95 % CI = 0.877–1.031, P = 0.225). Meta-analysis showed an association between the minor allele of rs752637 and RA in Europeans (OR = 0.858, 95 % CI = 0.789–0.932, P = 3.03 × 10^?5), but not in Asians (OR = 1.035, 95 % CI = 0.918–1.168, P = 0.572). No association was found between the rs2280714 polymorphism and RA susceptibility. This meta-analysis confirms that the IRF5 rs2004640, rs729302 and rs752637 polymorphisms are associated with RA susceptibility in different ethnic groups, especially in Europeans and Asians, but further study of this association is required in other ethnic groups.     

The l58Val/Met polymorphism of catechol-O-methyl transferase gene and prostate cancer risk: a meta-analysis

The association between COMT Val158Met polymorphism and prostate cancer has been evaluated. However, the results of these studies on the association remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. A comprehensive search was conducted to identify the eligible studies of COMT Val158Met polymorphism and prostate cancer risk. Summary odds ratios (OR) and 95 % confidence interval (CI) for COMT Val158Met polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage (Version 5.0) and Stata (Version 12.0). Six case–control studies, totally 4,118 persons including 2,143 cases and 1,975 controls, met the included criteria and thus were selected. Our analysis suggested that Val158Met polymorphism was associated with prostate cancer risk in overall population. Collectively, the results of the present study suggest that significant associations of COMT Val158Met polymorphisms with prostate cancer were observed (for additive model: OR = 1.068, 95 % CI = 1.002–1.138, P _{heterogeneity} = 0.363, P = 0.043; for dominant model: OR = 1.266, 95 % CI = 1.057–1.517, P _{heterogeneity} = 0.000, P = 0.011; for recessive model: OR = 1.050, 95 % CI = 0.961–1.146, P _{heterogeneity} = 0.558, P = 0.279; and Val allele versus Met allele OR = 0.932, 95 % CI = 0.894–0.971, P _{heterogeneity} = 0.272, P = 0.001). In the subgroup analysis, we detected no significant association between the COMT 158 Val/Met genotype and prostate cancer risk in Caucasian and Asian populations, while the contrary result for additive model (OR = 2.43, 95 % CI = 1.08–5.43, P _{heterogeneity} = 0.04, P = 0.03) in Asian populations. The result of this meta-analysis suggests that COMT l58Val/Met polymorphism might be contributed to the overall prostate cancer risk.     

The novel human MRC1 gene polymorphisms are associated with susceptibility to pulmonary tuberculosis in Chinese Uygur and Kazak populations

The MRC1 gene, encoding the human mannose receptor (MR), is a member of the C-type lectin receptors family. MR can recognize and bind to Mycobacterium tuberculosis by the extracellular structure, and play a role in antigen-presenting and maintaining a stable internal environment. This study aimed to investigate potential associations of SNPs in exon 7 of the MRC1 gene with pulmonary tuberculosis (TB). G1186A, G1195A, T1212C, C1221G, C1303T and C1323T were genotyped using PCR and DNA sequencing in 595 Chinese Uygur and 513 Kazak subjects. In the Uygur, the frequency of allele G (P = 0.031, OR = 1.29, 95 % CI = 1.02–1.62) and AA genotype (P = 0.033, OR = 1.64, 95 % CI = 1.04–2.60) for G1186A was lower in the pulmonary TB than healthy control and were significantly correlated with pulmonary TB. After adjustment for age and gender, G1186A was found to be additive models in association with pulmonary TB (P = 0.04, OR = 1.27, 95 % CI = 1.01–1.60). By calculating linkage disequilibrium, the frequency of haplotype GGTCCT (P = 0.032, OR = 0.75, 95 % CI = 0.57–0.97) and GGTCCC (P = 0.044, OR = 0.57, 95 % CI = 0.33–0.99) was significantly associated with pulmonary TB. No association was found between other SNPs and pulmonary TB. In the Kazak, all SNPs were not associated with pulmonary TB. Our results suggest that genetic factors play an important role in susceptibility to pulmonary TB at the individual level, and provide an experimental basis to clarify the pathogenesis of pulmonary TB.     

CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis

The aim of this study was to summarize results on the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism with systemic lupus erythematosus (SLE) susceptibility by using the meta-analysis. We searched all the publications about the association between CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism and SLE from PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang (Chinese). Previous CTLA-4 association studies with SLE, however, have produced inconsistent results. We have performed a meta-analysis to better assess the purported associations. A total of 17 independent studies (to June 2012) testing association between one or more CTLA-4 polymorphisms and SLE were used in this analysis. We have compared allele and genotype frequencies at two polymorphic sites found in exon-1 (at +49) and the promoter region (at ?1722). The data demonstrate that the exon-1 +49 polymorphism is associated with SLE susceptibility in Asian population. The overall risk, measured by odds ratio (OR), stratification by ethnicity indicates the exon-1 +49 GG+GA genotype is associated with SLE, at least in Asians (OR = 0.85, 95 % CI = 0.73–0.99, P = 0.04 for GG+GA vs. AA; OR = 0.85, 95 % CI = 0.72–1.00, P = 0.05 for AG vs. AA). Similar trends are found in allele-specific risk estimates and disease association. Overall, there was significant association between the 1722T/C polymorphism and overall SLE risks (OR = 0.78, 95 % CI = 0.63–0.97, P = 0.04 for GG+GA vs. AA, OR = 0.87, 95 % CI = 0.76–0.99, P = 0.04 for G vs. A) in Asian population.In summary, this meta-analysis demonstrates that the CTLA-4 promoter +49A/G and promoter ?1722C/T polymorphism may confer susceptibility to SLE, especially in Asian-derived population.     

Association of TGF-β1 +869C/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis

Many case–control studies have investigated the role of TGF-β1 gene +869C/T promoter polymorphism in autoimmune diseases, but the results are inconsistent. To clarify this point, we performed a meta-analysis based on all available studies in Pubmed, Elsevier Science Direct, Google Searching, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. Crude odds ratios (ORs) with 95 % confidence intervals were calculated to estimate the strength of the association. A fixed or random effects model was used on the basis of heterogeneity. A total of 21 papers including 2,693 cases and 3,036 controls were considered in the current meta-analysis. These studies encompass two ankylosing spondylitis (AS), eight rheumatoid arthritis (RA), four systemic lupus erythematosus (SLE), and seven systemic sclerosis (SSc). The results showed that TGF-β1 +869C/T promoter polymorphism were associated with susceptibility to RA (CC vs. TT: OR = 0.65, 95 % CI = 0.48–0.88, P = 0.005; CC vs. CT + TT: OR = 0.56, 95 % CI = 0.45–0.69, P = 0.000; C vs. T: OR = 0.81, 95 % CI = 0.71–0.93, P = 0.003). When stratified by race, significant association was observed only in Asian population. However, we failed to reveal the association between this gene promoter polymorphism and AS, SLE, and SSc. Therefore, this meta-analysis suggests a possible association between TGF-β1 +869C/T promoter polymorphism and RA, especially in Asian population.     

Effects of common polymorphisms rs2910164 in miR-146a and rs3746444 in miR-499 on cancer susceptibility: a meta-analysis

MicroRNAs (miRNAs) are a class of new non-coding RNA, which may play a more important role in the pathogenesis of human cancers. Rs2910164 in miR-146a and rs3746444 in miR-499 are shown to be associated with increased/decreased cancer risk. We performed a meta-analysis to systematically summarize the possible association. We retrieved the relevant articles from PubMed databases. Studies were selected using specific inclusion and exclusion criteria. ORs and 95% CIs were calculated to access the strength of association between microRNA polymorphism and cancer risk. All analyses were performed using the Stata software. Twenty-nine studies were included in this meta-analysis. There were not significant associations between miR-146a rs2910164 and miR-499 rs3746444 polymorphisms with overall cancer risk. In the subgroup analysis by ethnicity, significantly affected cancer risks were found among Asians for both rs2910164 (GC vs. GG: OR = 0.89, 95% CI = 0.82–0.96; CC vs. GG: OR = 0.80, 95% CI = 0.66–0.97; GC + CC vs. GG: OR = 0.86, 95% CI = 0.76–0.97; C vs. G: OR = 0.91, 95% CI = 0.82–1.00) and rs3746444 (GG + AG vs. AA: OR = 1.21, 95% CI = 1.00–1.46). In the tumor type subgroup analysis, rs2910164 C allele decreased the risk of hepatocellular carcinoma (C vs. G: OR = 0.89, 95% CI = 0.80–1.00) and cervical squamous cell carcinoma (C vs. G: OR = 0.72, 95% CI = 0.62–0.84). The rs2910164 in miR-146a and the rs3746444 in miR-499 are likely to be associated with cancer risk.     

A meta-analysis of the association of glutathione S-transferase P1 gene polymorphism with the susceptibility of breast cancer

Glutathione S-transferase P1 (GSTP1) is one of the important mutant sites for the cancer risk at present. The conclusions of the published reports on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer are still debated. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of breast cancer. The association reports were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. 35 investigations were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and breast cancer susceptibility, consisting of 40,347 subjects (18,665 patients with breast cancer and 21,682 controls). The association between GSTP1 A/G gene polymorphism and breast cancer risk was not found for overall population, Caucasians and Africans. Interestingly, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer in Asians (G allele: OR = 1.10, 95 % CI: 1.04–1.17, P = 0.001; GG genotype: OR = 1.36, 95 % CI: 1.14–1.62, P = 0.0008; AA genotype: OR = 0.92, 95 % CI: 0.85–0.98, P = 0.02). Furthermore, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer for the analysis of the controls from hospital. In conclusion, GSTP1 A/G gene polymorphism is associated with the breast cancer susceptibility in Asians. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer should be performed in further.     

NBS1 rs1805794G>C polymorphism is associated with decreased risk of acute myeloid leukemia in a Chinese population

As a key encoding protein gene of MRN (MRE11-RAD50-NBS1) complex, NBS1 plays a crucial role in maintaining genomic stability and preventing cell apoptosis, inflammation and tumorgenesis. Single nucleotide polymorphisms (rs2735383 and rs1805794) in NBS1 have been frequently studied in some cancers with discordant results in previous case–control studies. However, the relationship between these two functional polymorphisms and the susceptibility to acute myeloid leukemia (AML) in Chinese population has not been investigated. We performed a case–control study with 428 patients and 600 controls to detect the association between the two polymorphisms of NBS1 and the risk of AML in a Chinese population. The polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method was carried out to determine the genotypes of potential functional SNPs in NBS1 gene. The results showed that compared with the homozygous carriers rs1805794CC, rs1805794GC genotype was significantly associated with decreased risk of AML in total subjects (adjusted odds ratio (OR) = 0.50; 95 % CI = 0.37–0.67), the risk decreased even further in those carrying rs1805794GG genotype (OR = 0.23; 95 % CI = 0.16–0.34). No significant association was found between rs2735383C>G polymorphism and the risk of AML (OR = 0.93; 95 % CI = 0.71–1.22 for GC; OR = 0.78; 95 % CI = 0.53–1.13 for CC, P = 0.152). These findings indicated that rs1805794G/C polymorphism in NBS1 may play a protective role in mediating the risk of AML.     

DNA repair genes polymorphism and lung cancer risk with the emphasis to sex differences

Polymorphisms in nucleotide and base excision repair genes are associated with the variability in the risk of developing lung cancer. In the present study, we investigated the polymorphisms of following selected DNA repair genes: XPC (Lys939Gln), XPD (Lys751Gln), hOGG1 (Ser326Cys) and XRCC1 (Arg399Gln), and the risks they present towards the development of lung cancer with the emphasis to gender differences within the Slovak population. We analyzed 761 individuals comprising 382 patients with diagnosed lung cancer and 379 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism method. We found out statistically significant increased risk for lung cancer development between genders. Female carrying XPC Gln/Gln, XPC Lys/Gln+Gln/Gln and XRCC1 Arg/Gln, XRCC1 Arg/Gln+Gln/Gln genotypes had significantly increased risk of lung cancer corresponding to OR = 2.06; p = 0.04, OR = 1.66; p = 0.04 and OR = 1.62; p = 0.04, OR = 1.69; p = 0.02 respectively. In total, significantly increased risk of developing lung cancer was found in the following combinations of genotypes: XPD Lys/Gln+XPC Lys/Lys (OR = 1.62; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 2.14; p = 0.02). After stratification for genders, the following combinations of genotype were found to be significant in male: XPD Lys/Gln+XPC Lys/Lys (OR = 1.87; p = 0.03), XRCC1 Arg/Gln+XPC Lys/Lys (OR = 4.52; p = 0.0007), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 5.44; p < 0.0001). In female, different combinations of the following genotypes were found to be significant: XRCC1 Arg/Gln+hOGG1 Ser/Ser (OR = 1.98; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 3.75; p = 0.02), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 2.40; p = 0.04), XRCC1 Arg/Gln+XPC Gln/Gln (OR = 3.03; p = 0.04). We found out decreased cancer risk in genotype combinations between female patients and healthy controls: XPD Lys/Lys+XPC Lys/Gln (OR = 0.45; p = 0.02), XPD Lys/Gln+XPC Lys/Lys (OR = 0.32; p = 0.005), XPD Lys/Gln+XPC Lys/Gln (OR = 0.48; p = 0.02). Our results did not show any difference between pooled smokers and non-smokers in observed gene polymorphisms in the association to the lung cancer risk. However, gender stratification indicated the possible effect of heterozygous constitution of hOGG1 gene (Ser/Cys) on lung cancer risk in female non-smokers (OR = 0.20; p = 0.01) and heterozygous constitution of XPC gene (Lys/Gln) in male smokers (OR = 2.70; p = 0.01).     

Ewing Sarcoma: influence of TP53 Arg72Pro and MDM2 T309G SNPs

The Ewing Sarcoma is an important tumor of bone and soft tissue. The SNPs Arg72Pro of TP53 and T309G of MDM2 have been associated with many cancer types and have been differently distributed among populations worldwide. Based on a case–control design, this study aimed to assess the role of these SNPs in 24 Ewing Sarcoma patients, compared to 91 control individuals. DNA samples were extracted from blood and genotyped for both SNPs by PCR–RFLP and confirmed by DNA sequencing. The results showed an association between the G allele of the T309G and Ewing Sarcoma (P = 0.02). Comparing to the TT carriers, the risk of G allele carriers was 3.35 (95 % CI = 1.22–9.21) with P = 0.02. At the genotypic level, an association of the TT genotype with the control group (P = 0.03) was found. Comparing to the TT genotype, the risk of TG and GG was 2.97 (95 % CI = 1.03–8.58) with P = 0.04 and 5.00 (95 % CI = 1.23–20.34) with P = 0.02, respectively. No associations regarding the Arg72Pro SNP were found. Considering that the T309G has been associated with several types of cancer, including sarcomas, our results indicate that this SNP may also be important to Ewing Sarcoma predisposition.     

Association between PIN1 promoter polymorphisms and risk of nasopharyngeal carcinoma

Peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1) plays an important role in cell transformation and oncogenesis. Association between PIN1 promoter polymorphisms and cancer risk was reported in several cancers. This study aimed to evaluate the association between two single nucleotide polymorphisms (SNPs, ?667T>C, rs2233679 and ?842G>C, rs2233678) on PIN1 promoter and risk of nasopharyngeal carcinoma (NPC). The two SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism in a total of 334 native Chinese subjects consisting of 178 cases and 156 controls. The results indicated that the ?667CT heterozygote and ?667CC homozygote exhibited a significantly decreased risk of nasopharyngeal carcinoma when compared with ?667TT homozygote (OR = 0.639, 95 % CI = 0.452–0.903, p = 0.011 for ?667CT; and OR = 0.441, 95 % CI = 0.213–0.915, p = 0.038 for ?667CC, respectively). In the ?842G>C polymorphism, compared with ?842GG homozygote, only ?842CG heterozygote but not ?842CC homozygote had a significantly decreased risk of nasopharyngeal carcinoma (OR = 0.465, 95 % CI = 0.249–0.871, p = 0.010). Genotype in the two SNPs in patients showed no significant associations with the clinicopathologic features examined. Our study showed that the minor genotypes of PIN1 promoter (?667CT, ?667CC and ?842CG) were associated with decreased risk of NPC in a Chinese population, suggested that PIN1 promoter polymorphisms might play an important role in NPC carcinogenesis.     

Toll-like receptor (TLR) and matrix metalloproteinase (MMP) polymorphisms and periodontitis susceptibility: a meta-analysis

The aim of this study was to determine whether the toll-like receptor (TLR) and matrix metalloproteinase (MMP) polymorphisms confers susceptibility to periodontitis in ethnically different populations. A literature search using PubMed and Embase provided the data to conduct a meta-analysis on the associations between the TLR2 Arg753Gln, TLR4 Asp299Gly, Thr399Ile, MMP-1 ?1607 G1/G2 and MMP-9 ?1562 C/T polymorphisms and periodontitis. A total of 32 studies (14 on TLR polymorphisms and 18 on MMP polymorphisms) were considered in the meta-analysis. The meta-analysis showed no association between periodontitis and the TLR2 753Arg allele (Odds ratio [OR] = 0.962, 95 % confidence interval [CI] = 0.662–1.400, p = 0.841). Meta-analysis of the TLR4 Asp299Gly and Thr399Ile polymorphisms showed no association between periodontitis and the TLR4 299Asp allele in all study subjects (OR = 0.984, 95 % CI = 0.761–1.271, p = 0.900; OR = 1.030, 95 % CI = 0.748–1.418, p = 0.854). Meta-analysis showed an association between the MMP-1 ?1607 G2G2 genotype and periodontitis in Asians (OR = 3.778, 95 % CI = 1.210–11.80, p = 0.022). Meta-analysis containing only studies in Hardy–Weinberg equilibrium revealed no association between chronic periodontitis and the MMP-9 ?1562TT genotype (OR = 0.638, 95 % CI = 0.265–1.533, p = 0.315). This meta-analysis demonstrates a lack of association between the TLR2 Arg753Gln, TLR4 Asp299Gly, Thr399Ile, MMP-9 ?1562 C/T polymorphisms and periodontitis, but shows an association between the MMP-1 ?1607 G2G2 genotype and periodontitis in Asians.     

The association between the Lys751Gln polymorphism in the XPD gene and the risk of bladder cancer

The Lys751Gln polymorphism in the XPD gene have been suggested as a risk factor for bladder cancer, however the results were inconclusive. The aim of the current study is to assess the association by meta-analysis. A total of 15 case–control studies concerning the association between the XPD Lys751Gln polymorphism and bladder cancer risk were included in the meta-analysis. The results suggested that the Lys751Gln polymorphism was not associated with an increased risk of bladder cancer in the dominant model (OR = 1.03, 95 % CI 0.95–1.11, P = 0.53 for Lys/Gln+Gln/Gln vs. Lys/Lys) in overall analysis. In the subgroup analysis by ethnicity, no significant association was found in Caucasians or Asians. Other comparatives suggested a slight significant association between the polymorphism with the risk of bladder cancer in the recessive comparative (OR = 1.14, 95 % CI 1.02–1.29, P = 0.03). The current meta-analysis indicated that the Lys751Gln polymorphism in the XPD gene might be a risk factor for bladder cancer. In the future, more large-scale case–control studies are needed to validate our results.     

The Cdx-2 polymorphism in the VDR gene is associated with increased risk of cancer: a meta-analysis

The Cdx-2 polymorphism in VDR gene has been extensively investigated for association with cancer risk, however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of the Cdx-2 polymorphism in VDR and cancer risk by meta-analysis. All eligible case–control studies were searched in Pubmed, Embase, CNKI and Wanfang databases. Odds ratios (OR) with the 95 % confidence intervals (CI) were used to assess the association. A total of 12,906 cases and 13,700 controls in 18 case–control studies were included. The results indicated that the AA homozygote carriers had a 16 % increased risk of cancer, when compared with the homozygote GG and heterozygote AG (OR = 1.16, 95 % CI 1.05–1.29 for AA vs. GG+AG). In the subgroup analysis by ethnicity, significant elevated risks were associated with AA homozygote carriers in Caucasians (OR = 1.16, 95 % CI 1.01–1.33, and P = 0.04) and African Americans (OR = 1.31, 95 % CI 1.07–1.61, and P = 0.01). In the subgroup analysis by cancer types, the polymorphism was associated with increased risk of breast cancer (OR = 1.23, 95 % CI 1.04–1.46, and P = 0.02). This meta-analysis suggested that the Cdx-2 polymorphism of VDR gene would be a risk factor for cancer. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of VDR gene and cancer risk, more studies with large groups of patients are required.