Vitamin D receptor polymorphisms and the risk of cutaneous melanoma: a systematic review and meta-analysis

It has been hypothesized that polymorphisms in the vitamin D receptor (VDR) gene affect the risk of developing melanoma. However, results often are conflicting, and no meta-analysis has been performed to date on published data. Six studies (cases, 2152; controls, 2410) that investigated the association between 5 VDR polymorphisms (TaqI, FokI, BsmI, EcoRV, and Cdx2) and the risk of melanoma were retrieved and analyzed. The model-free approach was applied to meta-analyze these molecular association studies. Available data suggested a significant association between the BsmI VDR polymorphism and melanoma risk (pooled odds ratio [OR], 1.30; 95% confidence interval [CI], 1.11-1.53; P= .002; heterogeneity Cochran Q test, P> .1), and the population-attributable risk was 9.2%. In contrast, the FokI polymorphism did not appear to be associated with such risk (OR, 1.09; 95% CI, 0.99-1.21; P= .07; heterogeneity Cochran Q test, P> .1). For the TaqI and the EcoRV polymorphisms, significant between-study heterogeneity did not support genotype data pooling. Only 1 study investigated the Cdx2 variant, and the findings were negative. Current evidence is in favor of an association between 1 VDR gene polymorphism (BsmI) and the risk of developing melanoma. The current findings prompt further investigation on this subject and indirectly support the hypothesis that sun exposure may have an antimelanoma effect through activation of the vitamin D system.     

Meta-analysis of the relation between vitamin D receptor gene BsmI polymorphism and susceptibility to ovarian cancer

The role of vitamin D receptor (VDR) BsmI polymorphism in ovarian cancer development has been studied in various populations, but those results are discordant controversial and ambiguous. Thus, we performed a meta-analysis to assess the association between VDR BsmI polymorphism and susceptibility to ovarian cancer more precisely. Odds ratio (OR) and its 95 % confidence interval (95 % CI) were used for statistical analysis. Nine individual studies with a total 2,331 cases and 3,301 controls were included into this meta-analysis. There was no heterogeneity among those nine studies. Meta-analysis of total nine studies suggested that there was no association between VDR BsmI polymorphism and susceptibility to ovarian cancer (B vs. b, OR?=?1.02, 95 % CI?=?0.94–1.10, P?=?0.616, I ²?=?0 %; BB vs. bb, OR?=?1.02, 95 % CI?=?0.87–1.20, P?=?0.810, I ²?=?0 %; BB/Bb vs. bb, OR?=?1.05, 95 % CI?=?0.94–1.18, P?=?0.391, I ²?=?0 %; BB vs. bb/Bb, OR?=?0.99, 95 % CI?=?0.85–1.14, P?=?0.853, I ²?=?0 %). Meta-analysis of seven studies from Caucasians also showed that there was no association between VDR BsmI polymorphism and susceptibility to ovarian cancer. This meta-analysis suggests that there is no association between VDR BsmI polymorphism and susceptibility to ovarian cancer in Caucasians. Future studies from Asians or Africans are needed to further assess the above association.     

GSTP1 Ala114Val polymorphism and colorectal cancer risk: a meta-analysis

Studies investigating the association between cytochrome glutathione S-transferase P1 (GSTP1) Ala114Val polymorphism and colorectal cancer (CRC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine databases. Summary odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for GSTP1 polymorphism and CRC were calculated in a fixed effects model (the Mantel–Haenszel method) and a random effects model (the DerSimonian and Laird method) when appropriate. The pooled ORs were performed for co-dominant model (ValVal vs. AlaAla, AlaVal vs. AlaAla), dominant model (ValVal + AlaVal vs. AlaAla), and recessive model (ValVal vs. AlaVal + AlaAla). This meta-analysis included seven case–control studies, which included 3,173 CRC cases and 3,323 controls. Overall, the variant genotypes (ValVal and AlaVal) of the Ala114Val were not associated with CRC risk when compared with the wild-type AlaAla homozygote. Similarly, no associations were found in the dominant and recessive models. When stratifying for ethnicity, Hardy–Weinberg equilibrium in controls, study sample size, and source of controls, a significantly increased risk was observed among Asians (AlaVal vs. AlaAla, OR?=?1.67, 95 % CI?=?1.08–2.59; dominant model, OR?=?1.74, 95 % CI?=?1.14–2.67). No heterogeneity or publication bias was found in the present study. This meta-analysis suggests that the GSTP1 Ala114Val polymorphism may not be associated with CRC risk, while the observed increase in risk of CRC may be due to small-study bias.     

Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population

Recent studies have suggested that vitamin D is an important determinant of prostate cancer risk and inherited polymorphisms in the 3'-untranslated region (3'UTR) of the vitamin D receptor (VDR) gene are associated with the risk and progression of prostate cancer. This study was conducted to explore the association of VDR gene polymorphisms with prostate cancer risk in Japanese men who are considered to be much less influenced by environmental risk factors for prostate cancer. We studied 222 prostate cancer patients, 209 benign prostatic hyperplasia (BPH) patients, 128 male controls who were over 60 years old and without any evidence of prostate cancer or BPH, and 198 female controls. A PCR-RFLP method was used to determine three VDR gene polymorphisms in the 3'UTR characterized by restriction enzymes BsmI, ApaI and TaqI. In the BsmI polymorphism, heterozygosity or homozygosity for the absence of the BsmI restriction site was associated with one-third the risk of prostate cancer (P < 0.0001; odds ratio, 3.31; 95% confidence interval, 2.05-5.32) and with one-half the risk of BPH (P < 0.005; odds ratio, 2.07; 95% confidence interval, 1.33-3.22) compared with the male controls. The TaqI and ApaI polymorphisms did not show any significant association with either prostate cancer or BPH. The results indicate that the BsmI polymorphism in the VDR gene plays a significant role in protection against prostate cancer and BPH. Because of the racial difference in the strength of the linkage disequilibrium between the three polymorphisms, additional studies are required to apply the present results to other racial-ethnic groups.     

Association between vitamin D receptor poly(A) polymorphism and breast cancer risk: a meta-analysis

Vitamin D receptor (VDR) poly(A) is a common genetic polymorphism in the VDR gene, and it has been implicated to be associated with breast cancer risk. However, previous studies on the association reported inconclusive results. We performed this meta-analysis to comprehensively assess the association. Eligible studies were searched in PubMed and EMBASE databases. Odds ratio (OR) and its 95 % confidence interval (95 % CI) were used for statistical analysis. A total 6,631 cases and 6,718 controls from 11 case–control studies were finally included into the meta-analysis. Meta-analysis of total eligible studies showed that VDR poly(A) polymorphism was not associated with the risk of breast cancer (S versus L: OR?=?0.99, 95 % CI of 0.90–1.09, P?=?0.84; SS versus LL: OR?=?0.96, 95 % CI of 0.79–1.18, P?=?0.70; SS/LS versus LL: OR?=?0.96, 95 % CI of 0.83–1.12, P?=?0.63; SS versus LL/LS: OR?=?1.00, 95 % CI of 0.91–1.10, P?=?0.98). Meta-analysis of studies with high quality also showed that there was no association between VDR poly(A) polymorphism and breast cancer risk. In addition, in the subgroup analysis by ethnicity, no significant association was found among Caucasians. Therefore, the meta-analysis suggests that VDR poly(A) polymorphism is not associated with the risk of breast cancer. Large well-designed studies are necessary to clarify the possible association in Asians.     

Associations between vitamin D receptor polymorphisms and breast cancer risk

Many epidemiologic studies have investigated the association between vitamin D receptor (VDR) gene polymorphisms and breast cancer risk, but the results were inconsistent. We performed a meta-analysis of 31 studies on VDR polymorphisms, including FokI, BsmI, TaqI, and ApaI, and breast cancer risk published before May 2013. For FokI, the allele of f was found to be associated with increased risk of breast cancer compared with F (OR, 1.19; 95 % CI, 1.03–1.36). Patients with ff genotype were at significantly higher risk of breast cancer compared with those with FF genotype (OR, 1.95; 95 % CI, 1.66–2.29). In subgroup analysis by race, Fok1 polymorphism was significantly associated with breast cancer risk for Caucasian population (f vs. F: OR, 1.35; 95 % CI, 1.14–1.59; ff vs. FF: OR, 2.18; 95 % CI, 1.86–2.54; ff vs. FF?+?Ff: OR, 1.16; 95 % CI, 1.03–1.30). For ApaI, aa genotype was associated with increased breast cancer risk in Asian population based on four studies (aa vs. Aa?+?AA, OR, 1.49; 95 % CI, 1.12–1.98). No significant association was found between breast cancer risk and ApaI and TaqI polymorphism in different models and populations. Our updated meta-analysis showed that Fok1 polymorphism is associated with breast cancer risk both in general population and in Caucasian population. ApaI polymorphism might be associated with breast cancer risk in Asian population. Large well-designed epidemiological studies are necessary to clarify the risk identified in the current meta-analysis.     

Association of XRCC1 Arg399Gln Polymorphism with Colorectal Cancer Risk: A HuGE Meta Analysis of 35 Studies

Background: Non-synonymous polymorphisms in XRCC1 hase been shown to reduce effectiveness of DNArepair and be associated with risk of certain cancers. In this study we aimed to clarify any association betweenXRCC1 Arg399Gln and colorectal cancer (CRC) risk by performing a meta-analysis of published case-controlstudies. Materials and Methods: PubMed and Google Scholar were searched to explore the association betweenXRCC1 and CRC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate theassociation strength. Publication bias was assessed by Egger’s and Begg’s tests. Results: Up to January 2015, 35case control studies involving 9,114 CRC cases and 13,948 controls were included in the present meta-analysis.The results showed that the Arg399Gln polymorphism only under an allele genetic model was associated withCRC risk (A vs. G: OR 0.128, 95% CI 0.119-0.138, p<0.001). Also, this meta-analysis suggested that the XRCC1Arg399Gln polymorphism might associated with susceptibility to CRC in Asians (A vs G: OR 0.124, 95% CI0.112-0.138, p<0.001) and Caucasian (A vs G: OR 0.132, 95% CI 0.119-0.146, p<0.001) only under an allele geneticmodel. Conclusions: This meta-analysis confirms the association between XRCC1 Arg399Gln polymorphismand CRC risk and suggests that the heterogeneity is not strongly modified by ethnicity and deviation from theHardy-Weinberg equilibrium.     

A systemic review of glutathione S-transferase P1 Ilel05Val polymorphism and colorectal cancer risk

Objectives： To investigate the correlation between glutathione S-transferase P1 （GSTP1） Ilel05Val polymorphism and colorectal cancer （CRC） risk. Methods： Studies were identified to investigate the association between GSTP1 Ilel05Val polymorphism and CRC risk. Systematic computerized searches of the PubMed, Chinese National Knowledge Infrastructure, WANFANG and SinoMed were performed. Summary odds ratios （OR） and 95% confidence intervals （95 % CI） were used to measure GSTP 1 Ile 105Val polymorphisms and CRC risk. Results： A total of 23 retrospective studies were included in the meta-analysis. During all studies including 6,981 cases and 8,977 controls, sample sizes ranged from 146 to 2,144. Overall, the pooled results revealed that lie 105Val polymorphism was not associated with CRC risk and confused results were found in subgroup analyses. Further meta-analyses were conducted after excluding low-quality studies. GSTP1 Ilel05Val is associated with increased risk of CRC limited in studies with matched control. There was no significant heterogeneity in all genetic comparisons, but heterogeneity existed in subgroup analyses of heterozygous and dominant comparisons. The meta-regression analyses indicated that matched controls were the significant factor influencing between-study heterogeneity in all possible influential factors including published year, ethnicity, source of control, sample size, Hardy-Weinberg equilibrium （HWE） in control and matched controls. Sensitivity analysis revealed the pooled ORs were not changed before and after removal of each single study in all genetic comparisons, indicating the robustness of the results. Conclusions： GSTP1 Ilel05Val might be associated with increased risk of CRC. However, more high- quality case-control studies should be performed to confirm the authenticity of our conclusion.     

Association between IRS-1 Gly972Arg polymorphism and colorectal cancer risk

In order to make a comprehensive assessment of the potential association between one genetic variant in the insulin receptor substrate 1 (IRS-1) gene, rs1801278, and colorectal cancer (CRC) risk, we conducted a meta-analysis of four epidemiological studies, which included 3,708 CRC cases and 4,176 controls. The data showed that rs1801278 polymorphism was not associated with increased CRC risk in the overall population. When stratifying by the race, the results showed that the rs1801278 polymorphism was associated with increased CRC risk under dominant model in mixed populations. Based on this meta-analysis, we conclude that the IRS-1 rs1801278 polymorphism might be a risk factor for CRC development in mixed populations. Further studies, either with larger sample size or involving other single nucleotide polymorphisms (SNPs) and haplotypes of the IRS-1 gene, are necessary to clarify the contribution of IRS-1 rs1801278 in colorectal carcinogenesis.     

Vitamin D receptor rs2228570 polymorphism and susceptibly to ovarian cancer: a meta-analysis

The role of vitamin D receptor (VDR) rs2228570 polymorphism on the risk of ovarian cancer has been studied in many studies, but the relationship between VDR rs2228570 polymorphism and ovarian cancer is still unclear. We thus performed a meta-analysis of published studies to provide a comprehensive assessment of the association. Fourteen individual studies with a total of 10,964 subjects were finally included into the meta-analysis. We assessed the association by calculating the pooled odds ratio (OR) with 95 % confidence intervals (95 % CI). There was no heterogeneity among those included studies. Meta-analysis of 14 studies showed that the VDR rs2228570 polymorphism was associated with risk of ovarian cancer under three main comparison models (T versus C: OR?=?1.09, 95 % CI 1.03 to 1.15, P?=?0.004; TT versus CC: OR?=?1.17, 95 % CI 1.04 to 1.32, P?=?0.01; and TT/CT versus CC: OR?=?1.12, 95 % CI 1.03 to 1.21, P?=?0.007). Subgroup analysis in Caucasians further identified the obvious association. There was no evidence of publications bias. These data from the meta-analysis suggest that VDR rs2228570 polymorphism is associated with risk of ovarian cancer in Caucasians. More studies are warranted to assess the association between the VDR rs2228570 polymorphism and ovarian cancer in Asians and Africans.     

Adiponectin levels in patients with colorectal cancer and adenoma: a meta-analysis

Inconsistent results with regard to adiponectin levels in patients with colorectal cancer (CRC) and adenoma have been reported. To evaluate adiponectin levels in patients with CRC and adenoma, a meta-analysis on studies which compared adiponectin levels in patients with CRC or adenoma with healthy controls was carried out. A literature search was performed through Pubmed, EMBASE, and Science Citation Index Expanded database. Pooled-weighted mean differences and 95% confidence intervals (95%CI) were calculated by using random-effects models. Heterogeneity between studies was assessed using the Cochran's Q and I statistics. A total of 13 studies were identified, which included 2632 cases of CRC or adenoma and 2753 healthy controls. Adiponectin levels were significantly lower in patients with CRC or adenoma compared with healthy controls, with significant heterogeneity [weighted mean differences of -1.51 (95% CI: -2.42 to -0.59; Pheterogeneity<0.001) for CRC and -1.29 (95% CI: -2.01to -0.58; Pheterogeneity<0.001) for colorectal adenoma, respectively]. On stratified analysis of CRC, significant difference in adiponectin levels between patients with CRC and healthy controls was reported only in case-control studies or small sample size studies (n<100), but not in nested case-control studies or large sample size studies (n≥100). In addition, metaregression analysis indicated that study design and sample size partly contributed to the significant heterogeneity (P=0.022 for study design and P=0.018 for sample size, respectively). For colorectal adenoma studies, stratified analysis indicated that sample size was one of the heterogeneous factors. Sensitivity analysis showed that there were no changes in the direction of effect when any one study was excluded. No publication bias was detected. Adiponectin levels are lower in patients with CRC or colorectal adenoma compared with those in healthy controls. Future studies are warranted to clarify the association of adiponectin levels and carcinogenesis of the colorectum.     

Current evidence on the relationship between SNP309 polymorphism in the MDM2 gene and colorectal cancer risk

It has been demonstrated that MDM2 is a well-established negative regulator of the p53 protein and might be associated with a significantly earlier age of onset of several tumors, including colorectal cancer (CRC). In recent years, a T to G substitution (SNP309) in the promoter of MDM2 has been extensively studied as a potential CRC risk factor; however, the results are inconsistent. To derive a more precise estimation of association between MDM2 SNP309 polymorphism and CRC risk, we conducted a meta-analysis of 11 studies with 4,050 CRC cases and 3,688 controls. For MDM2 SNP309 polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, source of controls, and Hardy–Weinberg equilibrium (HWE) in controls, a significantly increased risk was observed among Asians (heterozygous model: odds ratio (OR)?=?1.21, 95 % confidence interval (CI)?=?1.06–1.39, P?=?0.005), population-based studies (heterozygous model: OR?=?1.17, 95 % CI?=?1.02–1.34, P?=?0.027), and among studies without the HWE (recessive model: OR?=?1.42, 95 % CI?=?1.03–1.94, P?=?0.030). When excluding three studies deviated from HWE, the significant results were also observed for heterozygous model in overall population (OR?=?1.16, 95 % CI?=?1.02–1.31, P?=?0.020). No publication bias was found in the present study. In conclusion, this meta-analysis suggests that MDM2 SNP309 polymorphism was associated with CRC susceptibility, especially among Asians. Further research is needed to assess possible gene–gene or gene–environment–lifestyle interactions on CRC.     

Vitamin D receptor gene ApaI polymorphism and breast cancer susceptibility: a meta-analysis

Vitamin D receptor (VDR) principally mediates the anticancer activities of vitamin D. Many studies investigated the association between VDR gene ApaI polymorphism and breast cancer, but the results were inconclusive. We performed this meta-analysis to evaluate the association between VDR gene ApaI polymorphism and breast cancer. Twelve studies with a total of 8,254 subjects were identified from PubMed and Wanfang databases. The pooled odds ratio (OR) and confidence intervals (95 % CI) were used to assess the association. The meta-analysis indicated that VDR gene ApaI polymorphism was not associated with risk of breast cancer (a vs. A: OR?=?0.97, 95 % CI 0.91–1.04, P?=?0.378; aa vs. AA: OR?=?0.97, 95 % CI 0.85–1.10, P?=?0.618; aa vs. AA + Aa: OR?=?1.00, 95 % CI 0.89–1.12, P?=?0.972; aa + Aa vs. AA: OR?=?0.95, 95 % CI 0.82–1.11, P?=?0.550). Subgroup analysis by ethnicity further showed that VDR gene ApaI polymorphism was not associated with risk of breast cancer in both Asians and Caucasians. These data from the meta-analysis indicate that VDR gene ApaI polymorphism is not associated with breast cancer susceptibility.     

Vitamin D receptor genotype and breast cancer in Latinas (United States)

Objective: Polymorphism in the vitamin D receptor (VDR) gene has been associated with variation in bone mineral density and with prostate cancer risk. The purpose of this study was to determine whether polymorphism in the VDR gene may also influence breast cancer risk.Methods: Polymorphisms in the 5 and 3 ends of the VDR gene were genotyped for 143 Latina women with breast cancer and 300 cohort controls.Results: Both the BsmI and poly-A polymorphisms in the 3 end of the VDR gene were associated with breast cancer risk, with a trend for increasing risk with increasing number of BsmI B alleles or short (S) poly-A alleles. Compared to subjects having two long poly-A alleles (genotype LL), odds ratios (and 95% confidence intervals) were 1.5 (1.0–2.3) and 3.2 (1.5–6.9) for subjects having genotypes SL and SS, respectively. Compared to BsmI genotype bb, odds ratios (and 95% confidence intervals) were 1.6 (1.1–2.5) and 2.2 (1.0–4.7) for genotypes Bb and BB respectively. The start codon polymorphism, FokI, was not associated with breast cancer risk.Conclusion: These results suggest that polymorphic variation in or near the 3 end of the VDR gene influences breast cancer risk in Latina women.     

Quantitative assessment of the association between microRNA-499 rs3746444 A/G polymorphism and cancer risk

Many epidemiological studies have evaluated the association between microRNA-499 rs3746444 A/G polymorphism and cancer risk, but published data are still inconclusive. Therefore, we performed a meta-analysis to evaluate the association between microRNA-499 rs3746444 A/G polymorphism and cancer susceptibility. The summary odds ratio (OR) with its 95 % confidence interval (CI) was calculated to evaluate the association. Seventeen case–control studies with a total of 7,974 cancer cases and 9,404 controls were finally included into this meta-analysis. Overall, microRNA-499 rs3746444 A/G polymorphism was significantly associated with increased risk in both the domain model (GG/AG versus AA: OR?=?1.17, 95 % CI, 1.03–1.33, P?=?0.02) and the heterozygote comparison model (AG versus AA: OR?=?1.15, 95 % CI, 1.01–1.32, P?=?0.03) when all studies were pooled into the meta-analysis. Subgroup analysis by ethnicity showed that association between microRNA-499 rs3746444 A/G polymorphism and cancer susceptibility was significant in Asians, but not in Caucasians. In the subgroup analysis by cancer types, no risk of breast, liver, or lung cancers were found significantly associated with microRNA-499 rs3746444 A/G polymorphism in any of the genetic models. In summary, this meta-analysis suggests that microRNA-499 rs3746444 A/G polymorphism is associated with increased susceptibility to cancer in Asians. However, more well-designed studies with large sample size are needed to validate this association among different kinds of cancers.     

XPG Asp1104His,XRCC2 rs3218536 A/G and RAD51 135G/C gene polymorphisms and colorectal cancer risk: A meta-analysis

Background: DNA repair mechanisms are crucial for sustaining DNA integrity and preventing carcinogenesis. The xeroderma pigmentosum group G (XPG), X-ray repair cross complementing group 2 (XRCC2) and RAD51 are candidate genes for DNA repair pathways. Methods: We performed a meta-analysis of 26 studies that assessed the impact of XPG Asp1104His, XRCC2 rs3218536 A/G and RAD51 135G/C polymorphisms on colorectal cancer (CRC) risk. This study included 10288 CRC patients and 11885 controls, and odds ratio (OR) with its 95% confidence interval (CI) were used to calculate the strength of association. Results: The results of overall meta-analysis suggested an association between the XPG Asp1104His polymorphism and CRC susceptibility in allele (OR=1.06; 95%CI=1.01-1.12) and heterozygote model (OR=1.16; 95%CI=1.02-1.31). In the subgroup analysis based on ethnicity and source of control, we found significantly increased CRC cancer risk in Asians (OR=1.12, 95%CI=1.04-1.21) and in hospital-based (OR=1.22, 95%CI=1.08-1.38) populations. Moreover, the RAD51 135 G/C polymorphism increased the risk of CRC in total using allele (OR=1.21) and recessive models (OR=1.62). However, XRCC2 rs3218536 A/G was not associated with the risk of CRC in total or in subgroups. Conclusions: According to the results of our meta-analysis, the XPG Asp1104His and RAD51 135 G/C polymorphisms might influence colorectal cancer risk.     

Association between the XRCC3 Thr241Met Polymorphism and Risk of Colorectal Cancer: a Meta Analysis of 5,193 Cases and 6,645 Controls

Background: Many studies have reported associations of the X-ray repair cross-complementing group 3(XRCC3) Thr241Met polymorphism with colorectal cancer (CRC) risk, but the results remained controversial.Hence, we performed the present meta-analysis with different inheritance models. Materials and Methods:We searched the PubMed and Google scholar databases for studies relating to associations between XRCC3Thr241Met polymorphism and risk of CRC. 16 studies with 5,193 cases and 6,645 controls were finally includedinto the meta-analysis. Results: We found that the XRCC3 Thr241Met polymorphism was associated withincreased CRC risk only under a dominant genetic model (CC+CT vs. TT: OR 0.575, 95%CI 0.498-1.665, p<0.001,Pheterogeneity =0.00, I2=83%). There was a significant association between XRCC3 Thr241Met polymorphism andCRC risk in Caucasian in the overall 8 studies under only in the heterozygote genetic model (CT vs. TT: OR=0.929,95%CI =0.806-1.070, P=0.308, Pheterogeneity =0.002, I2=57%). Four studies evaluated the XRCC3 Thr241Metpolymorphism and CRC risk in Asians. Two genetic models of the XRCC3 polymorphism were significantlycorrelated with increasing risk in Asians (dominant model: CC+CT vs. TT: OR= 0.609, 95%CI=411-0.902,P=0.013, Pheterogeneity =0.54, I2=0.00%; Allele model: C vs. T: OR=0.708, 95 %=CI 0.605-0.829, p=0.000, Pheterogeneity =0.000, I2=92%). The sensitivity analysis suggested stability of this meta-analysis and no publication bias wasdetected. Conclusions: In conclusion, this meta-analysis indicates that XRCC3 Thr241Met shows an increasedCRC risk, particularly in Asians rather than Caucasians.     

Null genotype of GSTT1 contributes to colorectal cancer risk in Asian populations: evidence from a meta-analysis

Background/Aims: Studies of associations between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and risk of colorectal cancer (CRC) in Asian populations have reported controversial results. Thus, a meta-analysis was performed to clarify the effects of GSTT1 polymorphism on the risk of developing colorectal cancer. Methods: A literature search of PubMed and EMBASE up to June 7, 2011 was conducted and 13 eligible papers were finally selected, involving totals of 4,832 CRC cases and 7,045 controls. Subgroup analyses were performed according to the sample size and the research designwith the software programs Review Manager (version 5.0.10) and STATA (version 9.2). Results: Analyses of all relevant studies showed an increased CRC risk was significantly associated with the null genotypes of GSTT1 (OR=1.09, 95%CI=1.01-1.17, POR=0.027; I2=40.2%). Besides, a more obvious association was observed after heterogeneity was eliminated (OR=1.13, 95%CI 1.04-1.23, POR=0.002; I2=0.0%). Subgroup analyses and sensitivity analysis further identified an association in Asians. Conclusions: This meta-analysis demonstrated the GSTT1 null genotype to be associated with an increased risk of CRC in Asian populations.     

Association of Benign Prostate Hyperplasia with Polymorphisms in VDR,CYP17, and SRD5A2 Genes among Lebanese Men

Background: The aim of the study was to investigate any associations between benign prostate hyperplasia(BPH) and single nucleotide polymorphisms (SNPs) in the VDR gene (FokI, BsmI, ApaI and TaqαI loci) and theCYP17 gene (MspA1I locus), as well as TA repeat polymorphism in SRD5A2 gene among Lebanese men. Materialsand Methods: DNA extracted from blood of 68 subjects with confirmed BPH and 79 age-matched controls wassubjected to PCR/PCR-restriction fragment length polymorphism analysis. The odds ra=tio (OR) of having agenotype and the relative risk (RR) of developing BPH for having the genotype were calculated and the alleleswere designated risk-bearing or protective. Results: Our data indicated that the A and B alleles of the VDR ApaIand BsmI SNPs were highly associated with increased risk of BPH (p=0.0168 and 0.0002, respectively). Moreover,63% of the controls compared to 43% of the subjects with BPH were homozygous for none of the risk-bearingalleles (p=0.0123) whereas 60% of the controls and 28% of the subjects with BPH were homozygous for two ormore protective alleles (p<0.0001). Conclusions: For the first time, our study demonstrated that ApaI and BsmIof the VDR gene are associated with risk of BPH among Lebanese men. Our study also indicated that overallpolymorphism profile of all the genes involved in prostate physiology could be a better predictor of BPH risk.     

Polymorphisms in the vitamin D receptor gene and the lung cancer risk

The relationship between the vitamin D receptor (VDR) polymorphisms and the susceptibility to lung cancer remains unclear. The present meta-analysis was performed to estimate the polymorphisms of VDR and lung cancer risk. The pooled odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were calculated. Subgroup analysis by smoking status was carried out for further elucidation. The VDR BsmI polymorphism seemed to be negatively associated with the lung cancer risk (A vs. G, OR?=?0.71, 95 % CI, 0.52–0.96; GA vs. GG, OR?=?0.54, 95 % CI, 0.35–0.83; AA + GA vs. GG, OR?=?0.55, 95 % CI, 0.36–0.84), particularly among the smokers (AA + GA vs. GG, OR?=?0.39, 95 % CI, 0.21–0.72). The VDR ApaI variant genotypes did not alter the risk of lung cancer under all gene models in overall analysis. However, smokers carrying the variant G allele were more susceptible to lung cancer (G vs. T, OR?=?1.60, 95 % CI, 1.14–2.25). The polymorphism of VDR TaqI was related to a decreased risk of lung cancer (C vs. T, OR?=?0.62, 95 % CI, 0.26–1.46; CC vs. TT, OR?=?0.44, 95 % CI, 0.21–0.91; TC vs. TT, OR?=?0.58, 95 % CI, 0.38–0.90; CC + TC vs. TT, OR?=?0.55, 95 % CI, 0.36–0.84). Besides, the CC + TC carriers in the smokers were at a significantly reduced risk of lung cancer (CC + TC vs. TT, OR?=?0.48, 95 % CI, 0.16–1.44). The study supports that the polymorphisms of VDR BsmI and TaqI play protective roles in the lung carcinogenesis, particularly among the smokers. The association of VDR ApaI polymorphism with the lung cancer risk needs to be further elucidated.