Top PDF Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies.

Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies.

Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies.

The Bsm1 polymorphism is located at the 3 9 end of the VDR gene. It does not appear to change the nature of the translated VDR protein [53]. However, this polymorphism is linked in a haplotype with the variable-length poly A sequence within the 3 9- untranslated region, which affects the VDR mRNA stability [54]. On the other hand, the Bsm1, Taq1 and Apa1 polymorphisms are all in the same linkage disequilibrium block. These polymorphisms have been widely investigated, but with differing results. Consis- tent with a previous meta-analysis, our finding showed no significant association of these three genetic variations with breast cancer risk. Several studies have been performed to examine the VDR haplotypes [9,13,14,18,35], but these results were also conflicting. McCullough et al. has investigated haplotypes that involved Bsm1(B/b), Apa1(A/a), Taq1(T/t) and a poly-A repeat(S/ L), but they failed to find significant association between any haplotype and breast cancer risk [13]. However, in a Caucasian population the baTL has been reported to increase the risk of breast cancer [9,35]. It is unclear whether chance or underlying differences in populations led to these inconsistencies. Due to the limited information available about these polymorphisms, we could not conduct an analysis for linkage disequilibrium and haplotypes.
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The Association between VEGFR Gene Polymorphisms and Stroke: A Meta-Analysis.

The Association between VEGFR Gene Polymorphisms and Stroke: A Meta-Analysis.

Several published articles investigated the relationship between VEGF receptor gene poly- morphisms and stroke, but they failed to reach the same conclusion. This meta-analysis was performed to identify the relationships between VEGF receptor gene and the risk of stroke. The PubMed, Embase, China National Knowledge Infrastructure (CNKI) database, Wanfang Chinese database, and VIP Chinese database were systemically searched. Data was extracted by two independent reviewers. The pooled odds ratio (OR) with 95% confi- dence interval (CI) were calculated. 5 case-control studies with a total of 2904 patients with stroke and 2824 control subjects were included, including 2904 cases and 2824 controls for -604T>C, 2733 cases and 2663 controls for +1192C>T, and 2733 cases and 2663 controls for +1719A>T. Under the dominant and recessive models, respectively, the overall ORs and 95% CIs of -604 C were 0.749, 0.493–1.138 (P = 0.176) and 0.819, 0.544–1.234 (P = 0.340); the overall ORs and 95% CIs of +1192 T were 1.148, 0.876–1.504 (P = 0.318) and 1.611, 1.004–2.586 (P = 0.048); the overall ORs and 95% CIs of +1719 T were 1.227, 0.932–1.615 (P = 0.146) and 1.139, 1.015–1.279 (P = 0.027). Our finding indicates that +1192C>T and +1719A>T may be associated with the risk of stroke, but not -604T>C.
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Association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and Graves' disease risk: a meta-analysis of 11 case-control studies.

Association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and Graves' disease risk: a meta-analysis of 11 case-control studies.

IL-1B is a pluripotential proinflammatory cytokine that primarily produced by B lymphocytes, monocytes and fibroblasts. It is an important mediator for the inflammatory responses and play key roles in the triggering of immune functions, effecting nearly every cell type. IL-1B influenced thyroid cells via a number of underlying mechanisms, including down-regulation of thyroid peroxidase gene expression [31], induction of dissociation of the junctional complex [32], and inhibition of cyclic adenosine monophosphate (cAMP) and thyroglobulin production [33]. In the development of GD, infiltration of the thyroid by activated immune cells results in local release of IL-1B. It has been observed that IL-1B induces the production of IL-6, IL-8, intercellular adhesion molecule-1 (ICAM-1), and other inflammatory mediators [34–36]. IL-1B also enhances T cell-dependent antibody produc- tion by augmenting CD40 ligand and OX40 expression on T cells [37]. IL-1B was shown to promote differentiation of T-helper 17 (Th17) cell, the proportion of which was reported to be higher in intractable GD than that of GD in remission [38]. Therefore, IL1B may play a role in the pathogenesis of thyroid autoimmunity. In this meta-analysis, we observed that the IL1B (-511) TT genotypes were protective against GD in Asians. This SNP may affect protein expression and function [27,39], resulting in down-regulation of inflammatory responses and resistance to develop GD. Several reasons may account for the discrepancy of results between Asians and Caucasians. First, distinct genetic background may play a role. Second, GD is a complex disease which is also related to environmental factors. Genetic susceptibility to GD may be modified by a variety of environmental exposures, leading to differences in genetic associations. Between-study heterogeneity was identified in several pooled analyses. However, when we undertook subgroup analyses according to ethnicity, heterogeneity was greatly reduced, suggesting that ethnicity was the main source of heterogeneity. Other potential factors, such as study design, sample size and genotyping methods, might also contribute to heterogeneity.
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Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case-control studies.

Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case-control studies.

suppression, tumor cell invasion, metastasis, and angiogenesis, which are all crucial in the development and progression of cancer [39,41,42]. It was shown that polymorphisms in the promoter of COX-2 may exert profound effects on gene transcriptional activity by altering the binding capacity of certain nuclear proteins, there- by affecting expression of COX-2 enzyme [43]. COX-2 2765G.C is a functional polymorphism located at 765 bp upstream (2765 bp) from the transcription starting site. It changes a putative stimulatory protein (Sp1) binding site in the promoter of COX-2 between 2766 and 2761 bp [44], but it creates an E2 promoter factor (E2F) binding site, leading to high transcription activity and increased COX-2 expressions which might be involved in the development of cancers [45]. More importantly, the homozygous variant genotype COX-2 2765CC has been shown associated with increased risk for many different types of cancers, including breast cancer [46], ovarian cancer [47], hepatocellular carcinoma [48] and lung cancer [49].
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Association between the ERCC5 Asp1104His polymorphism and cancer risk: a meta-analysis.

Association between the ERCC5 Asp1104His polymorphism and cancer risk: a meta-analysis.

As a structure-specific endonuclease and also a 59-39 exo- nuclease, the ERCC5 protein is required for two sub-pathways in NER. One is TCR, which preferentially removes DNA damage in the transcribed DNA strand of active genes; the other is global genomic repair (GGR), which removes lesions throughout the genome [15,16]. Additionally, ERCC5 also possesses some secondary functions independent of its cleavage activity in supporting a role of TFIIH in receptor-mediated transcription [17,18]. Furthermore, data from S. cerevisiae studies demonstrate a role for Rad2 (the ERCC5 homolog) in RNA polymerase II- mediated transcription [19]. In addition, ERCC5 is thought to have a possible role in the removal of oxidative damage by BER and possibly other pathways [20,21]. Numerous studies using various tumor cell lines or tissues indicates that ERCC5 plays a key role in carcinogenesis and that its deficiency leads to DNA repair defects, genomic instability, failure of modulation of gene transcription [22–26]. Genetic disorders resulting from mutations in the ERCC5 gene, such as xeroderma pigmentosum (XP), Cockayne syndrome (CS), and tri-chothiodystrophy (TTD), un- derscore the biological importance of this gene [14], and most of these syndromes follow a recessive genetic model, in which heterozygotes are unaffected, but mutant homozygotes manifest the disease [27].
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Association of TLR2 and TLR4 polymorphisms with risk of cancer: a meta-analysis.

Association of TLR2 and TLR4 polymorphisms with risk of cancer: a meta-analysis.

In term of stratified analyses by races, our findings indicated that TLR2 2196 to 2174 del had an significant association with cancer risk in Caucasians and South Asians, but not in East Asians. However, the association between TLR4 rs4986791 and cancer risk was significant in both South Asians and East Asians, but not in Caucasians. These differences may be induced by different genetic backgrounds and environmental exposures, as indicated by the difference of minor allele frequency in controls among the two populations (Table 1). For example, the MAF of TLR2 2196 to 2174 del in Caucasian controls varied from 0.05 to 0.15, but that in Asians was from 0.12 to 0.38. Allele frequency might reflect the natural selection pressures or a balance by other related functional genetic variants and/or environmental expo- sures. We also searched some public databases, such as Hapmap (http://hapmap.ncbi.nlm.nih.gov/) and SNPinfo (http://snpinfo. niehs.nih.gov/), and found that rs4986790 was in high linkage disequilibrium (LD) with rs4986791 in Caucasians (r 2 = 1), but not data was available in Asians because of low allele frequency of these two SNPs. In our analysis, the associations of rs4986790 and rs4986791 with cancer risk were consistent in Caucasians, but inconsistent in Asians. These findings further indicate that the effect of genetic variants on cancer risk may be different between multiple ethnic groups. Some limitations and potential bias should be addressed. First, the subgroups may have a relatively lower power based on a small number of studies. Second, a more precise analysis should be conducted, if individual data were available, allowing for the adjustment by some co-variants such as age, gender and other environmental factors. However, these informa- tion were unavailable from most of studies. Third, the controls in the included studies were recruited from different ways and not uniformly defined, which may have induced some bias for the meta-analysis. Last, the gene-gene interaction is important for the development of complex diseases including cancer because single genetic variation may only have a modest effect [63,64]. However, the original genotyping data of each publication was unavailable and we could not carry out gene-gene interaction analysis in this study.
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Association between CTLA-4 60G/A and -1661A/G polymorphisms and the risk of cancers: a meta-analysis.

Association between CTLA-4 60G/A and -1661A/G polymorphisms and the risk of cancers: a meta-analysis.

the presence of G allele, thereby regulate the function of CTLA-4 [29]. In our meta-analysis, we found significant association between CTLA-4 -1661A/G polymorphism and increased cancer risk in heterozygote model, dominant model and allele model. The results were very robust, which did not vary materially when we performed the sensitivity analysis (exclusion the study with controls not in HWE). In the subgroup analysis by ethnicity, we observed a significant association between increased cancer risk and Asian population, the sensitivity analysis by deleting studies with controls deviating from HWE still showed a significant association, which demonstrated our results were reliable. However, we did not found any significant increased cancer risk in Caucasians, ethnicity may be an essential biological factor which influences CTLA-4 - 1661A/G polymorphism through gene to gene interaction. Moreover, when the data were stratified by cancer type, a significant increased cancer risk was observed in gastric cancer, breast cancer and other cancers. However, after we performed the sensitivity analysis, we did not found significant association between increased cancer risk and other cancers. In the subgroup analysis by source of controls, we found significant association between increased cancer risk and population based group. The remaining pooled ORs from this analysis were insignificant. Recent studies reported that CTLA-4 blockade could enhance the effect of a potent p53-expressing MVA vaccine, enhance the CTL response to p53 [44,45]. These results suggest that the CTLA-4 - 1661A/G polymorphism may be affect the expression and function of p53, and may be related to the tumor development.
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Methylenetetrahydrofolate Reductase  Polymorphisms at Familial Bladder Cancer: Case Report

Methylenetetrahydrofolate Reductase Polymorphisms at Familial Bladder Cancer: Case Report

In previous studies, for the association between the MTHFR C677T and A1298C polymorphisms and bladder cancer risk, it has been observed that the variant genotype MTHFR 677TT was associated with an increased risk of bladder cancer, com- pared with the wild-type homozygote 677CC. Folate deiciency leads to decreased DNA methylation and such insuiciency may result in carcinogenesis by inducing genomic instability or acti- vation of oncogenes [2]. In a meta-analysis, 13 diferent articles were identiied to evaluate the association between C677T or A1298C polymorphisms in the MTHFR gene and the risk for bladder cancer. According to this meta-analysis, there was no signiicant association between the C677T polymorphism and the susceptibility to bladder cancer risk in the overall analysis, but signiicant relationships were detected in the mixed and Asian populations rather than in Europeans and Africans. This is important, because the allele and genotype distribution of MTHFR C677T locus is diferent in diferent races [4]. Safarine- jad et al [5] found that the 1298C allele (CA+CC, heterozygotes and homozygotes) was signiicantly associated with increased risk of bladder cancer in Asians. Similarly, individuals who car- ried the 1298 CC genotype (homozygote) had a higher risk for bladder cancer in Asians. Moreover, this increased association was also found in Africans. However, the CC genotype (homozy- gosity) played a protective role for bladder cancer in Europeans [5]. In a study, association between MTHFR C677T and gas- tric cancer, leucemia and colorectal cancer were also among the most noteworthy associations. Because of its role in a key pathway, the MTHFR C677T variant may have a true impact on cancer risk [6]. In a study by Ozarda et al [13], frequencies of C and T alleles and also frequencies of TT and CC genotypes were investigated in 402 healthy individuals. The frequency of MTHFR T677T genotype was found as 7.7% and the frequency of MTHFR C677T genotype was found as 40%, in males. In fe- males, these rates were as 9.1% and 42.2%, respectively [7]. MTHFR genes play a central role in folate metabolism, and studies have revealed that the cancer risk associated with MTHFR polymorphisms may be modulated by folate intake. The decreased expression of MTHFR by hypermethylation due to the C677 polymorphism may cause an increased risk of DNA hypomethylation of oncogenes, which may not be corrected by other DNA repair enzymes, resulting in a higher susceptibility to bladder cancer in carriers of the 677TT genotype [8].
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Investigation of CD28 gene polymorphisms in patients with sporadic breast cancer in a Chinese Han population in Northeast China.

Investigation of CD28 gene polymorphisms in patients with sporadic breast cancer in a Chinese Han population in Northeast China.

Methodology/Principal Findings: Our research subjects consisted of 565 female patients with sporadic breast cancer and 605 age- and sex-matched healthy controls. In total, 12 single nucleotide polymorphisms (SNPs) in the CD28 gene were successfully determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The relationship between the CD28 variants and clinical features, including histological grade, tumor size, lymph node metastasis, human epidermal growth factor receptor 2 (C-erbB2), estrogen receptor (ER), progesterone receptor (PR), and tumor protein 53 (P53) status were analyzed. A statistically significant association was observed between rs3116496 and breast cancer risk under different genetic models (additive P = 0.0164, dominant P = 0.0042). Different distributions of the rs3116496 ‘T’ allele were found in patients and controls, which remained significant after correcting the P value for multiple testing using Haploview with 10,000 permutations (corrected P = 0.0384). In addition, significant associations were observed between rs3116487/rs3116494 (D’ = 1, r 2 = 0.99) and clinicopathological features such as C-erbB2 and ER status, in breast
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There is no association between microRNA gene polymorphisms and risk of triple negative breast cancer in a Chinese Han population.

There is no association between microRNA gene polymorphisms and risk of triple negative breast cancer in a Chinese Han population.

Triple-negative breast cancer (TNBC) is defined by the lack of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). It is characterized by aggressive behavior, poor prognosis and lack of targeted therapies. MicroRNA (miRNA) as a novel modulator of gene expression has played an important regulatory role in the malignancy. Dysregulation and/or mutation of the miRNAs may also contribute to the TNBC susceptibility since it is associated with the expression of ER, PR and HER2. Single nucleotide polymorphisms (SNPs) in miRNAs may be extremely relevant for TNBC. We tried to validate the hypothesis that genetic variations in miRNA are associated with TNBC development, and identify candidate biomarkers for TNBC susceptibility and clinical treatment. We screened the genetic variants in all miRNA genes listed in the public database miRBase and NCBI. A total of 23 common SNPs in 22 miRNAs, which tagged the known common variants in the Chinese Han people with a minor allele frequency greater than 0.05, were genotyped. This case-control study involved 191 patients with TNBC and 192 healthy female controls. Frequencies of SNPs were compared between cases and controls to identify the SNPs associated with TNBC susceptibility. No significant association was found between TNBC risk and the SNPs in the miRNA genes in the Chinese Han people (P.0.05), but this warrants further studies.
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Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

To the best of our knowledge, the present study is the most comprehensive meta-analysis to date to have assessed the relationship between the miRNA polymorphisms and cancer risk. Nevertheless, our meta-analysis had some limitations common to these types of studies. First, the present meta-analysis only included case-control studies, most of which were hospital based and excluded 12 cohort studies to avoid potential heterogeneity in comparing results. Thus, the controls may not reflect the representative element of the source population. Second, the difference in the geographic areas (environmental factors) and genetic backgrounds of the study cohort in each article could influence the results. Third, the low sample size in some of the included studies might influence the statistical power to better evaluate the association between miRNA polymorphisms and overall cancer, especially in subgroup analysis. Fourth, gene-gene and gene-environment interactions were not analyzed which might alter the associations between miRNA gene polymorphisms and cancer. Also, a more precise analysis stratified by variables such as age, sex etc. could not be performed due to limitations of the data which also restricted our ability to detect possible sources of heterogeneity.
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Association between the melatonin receptor 1B gene polymorphism on the risk of type 2 diabetes, impaired glucose regulation: a meta-analysis.

Association between the melatonin receptor 1B gene polymorphism on the risk of type 2 diabetes, impaired glucose regulation: a meta-analysis.

Deviation from Hardy–Weinberg equilibrium for controls was examined by x 2 tests. Odds ratio (OR) with 95% confidence intervals (CIs) was used to assess the strength of association between the MTNR1B gene polymorphism and T2D risk. The per-allele OR of the risk allele was compared between cases and controls. Then, we examined the association between risk genotype of these polymorphisms and T2D susceptibility using dominant and recessive genetic models. Heterogeneity across individual studies was calculated using the Cochran chi-square Q test followed by subsidiary analysis or by random-effects regression models with restricted maximum likelihood estimation [11–13]. Random-effects and fixed-effect summary measures were calcu- lated as inverse variance-weighted average of the log OR. The results of random-effects summary were reported in the text because it takes into account the variation between studies. The 95% CIs were constructed using Woolf’s method [14]. The significance of the overall OR was determined by the Z-test. Sample size (No. cases $1000 or ,1000) and ethnicity were prespecified as characteristics for assessment of heterogeneity. Ethnic group was defined as Caucasian (i.e., people of European origin), East Asian (e.g., Chinese, Japanese, and Korean), and South Asian (e.g., Indian, and Pakistani). In addition, sample size, ethnicity, gender distribution in cases and controls, genotyping
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A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer.

A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer.

vitamin D metabolite levels in many of the blood samples taken from these men in 1982 and determined their FokI genotype. Two-thirds of the men had insufficient blood levels of vitamin D metabolites in the winter/spring; almost one-third had a vitamin D deficiency. Men whose blood levels of both metabolites were below average were twice as likely to develop aggressive prostate cancer as those in whom both levels were above average. Compared with men with high blood levels of 25(OH)D and the FokI FF or Ff genotype, men with low 25(OH)D levels and the FokI ff genotype were 2.5 times as likely to develop aggressive prostate cancer. However, men with the ff genotype were not at higher risk if they had sufficient 25(OH)D levels. Among men with the ff genotype, sufficient 25(OH)D levels might therefore protect against prostate cancer, especially against the clinically aggressive form. What Do These Findings Mean? These findings confirm that many US men have suboptimal levels of circulating vitamin D. This vitamin is essential for healthy bones, so irrespective of its effects on prostate cancer, vitamin D supplements might improve overall health. In addition, this large and lengthy study reveals an association between low levels of the two vitamin D metabolites and aggressive prostate cancer that is consistent with vitamin D helping to prevent the progression of prostate cancer. It also indicates that the VDR FokI genotype modifies the prostate cancer risk associated with different blood levels of vitamin D. Together, these results suggest that improving vitamin D status through increased exposure to sun and vitamin D supplements might reduce prostate cancer risk, particularly in men with the FokI ff genotype. Because the study participants were mainly of European descent, the researchers caution that these results may not apply to other ethnic groups and note that further detailed studies are needed to understand fully how vitamin D affects prostate cancer risk across the population.
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Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.

Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.

Several studies have demonstrated that individuals with MTHFR 677 TT genotype, lack of vitamins B6 and B12, methionine and folate, and high consumption of alcohol are at increased risk of developing colorectal tumors [39–42]. How- ever, no studies have reported these gene-nutrient interactions with the risk of AML. The present study was lack of data to estimate the association of gene-nutrient and risk of AML. These interesting clues may be useful for future research. Dietary intake of several nutrients could influence the distribu- tion of intracellular folate metabolites. Vitamins B6 and B12 may affect DNA synthesis and MTHFR enzyme activity. Moreover, high consumption of alcohol might take place of more nutritious foods, which may lead to the intake deficiency of folate and B vitamins [43]. Deficiency of folate is associated with carcinogenesis mainly in two ways [8]: (1) The conversion of dUMP to dTMP, using for DNA synthesis and repair, demands methyl group donated by 5, 10-methyleneTHF, so lack of folate can intervene thymidylate biosynthesis and then lead to leads to errors in DNA synthesis, strand breakage, and chromosomal repair. (2) Low-level 5-methylTHF may result in
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Association between 5p12 genomic markers and breast cancer susceptibility: evidence from 19 case-control studies.

Association between 5p12 genomic markers and breast cancer susceptibility: evidence from 19 case-control studies.

In meta-analysis, heterogeneity evaluation was always conduct- ed in statistical analysis. Thus, several subgroup meta-analyses were performed according to ethnicity, sample size. In the stratified analysis by ethnicity, significant associations were found in Asians and Caucasians for the two polymorphisms in all genetic models; while no associations were detected among Africans. Such result could be due to the limited number of studies among Africans/African-Americans, which had insufficient statistical power to detect a slight effect or different linkage disequilibrium (LD) pattern of the two polymorphisms among Africans. Besides, the frequencies of the risk-association alleles in 5p12 are similar in European and Asian populations, but substantially lower in African descent [25,29–31]. Furthermore, ER status may be particularly important given that some GWAS findings are specific to ER-positive and ER-negative cancers [5,33] and because a higher proportion of African American are diagnosed with ER- negative cancers [34,35], resulting in risk differences. Moreover, it is possible that variation at this locus has modest effects on BC, but environmental factors may predominate in its progress, and mask the effects of this variation. Specific environmental factors like lifestyle and diabetes that have been already well studied in recent decades [36]. It is still unknown whether the lifestyle character- istics of different populations influence the association between these polymorphisms and BC. The unconsidered factors mixed together may cover the role of the two polymorphisms in Africans/ African-Americans. Meta-analysis is often dominated by a few large studies, which markedly reduces the evidence from smaller studies. By considering sample size, significantly increased BC susceptibility in 5p12 common variations was also found both in Table 3. Results of meta-analysis for 5p12-rs4415084 polymorphism and BC risk.
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ESR1 Gene Polymorphisms and Prostate Cancer Risk: A HuGE Review and Meta-Analysis.

ESR1 Gene Polymorphisms and Prostate Cancer Risk: A HuGE Review and Meta-Analysis.

To explore the association between ESR1 gene polymorphisms and prostate cancer risk, we performed a meta-analysis on 2,165 prostate cancer cases and 3,361 controls. This is the first meta- analysis exploring the relationship between prostate cancer and the ESR1 gene polymorphisms. When all the eligible studies were pooled into the meta-analysis, the results showed that ESR1 PvuII (C.T) and XbaI (A.G) polymorphisms were not associated with the risk of prostate cancer, yet many studies have inferred that ESR1 gene polymorphisms were related to the onset and develop of prostate cancer [11,12,26,37,41–43]. A possible reason for the controversy is that a considerable degree of heterogeneity existed among the other studies due to differences in sample sizes, exposure estimates, ethnicity, source of controls and other potential confounding variables. Therefore, we performed a stratified analysis based on ethnicity and country. The results showed that ESR1 PvuII (C.T) polymorphism might increase the risk of prostate cancer among Asian populations, especially among Indian population. ESR1 XbaI (A .G) polymorphism was confirmed to be associated with increased risk of prostate cancer among American population under the allele model, but not among Japanese and Indian populations. However, pooled estimates for Indian population was slightly higher than that for American population, and only pooled OR under the allele model was significant and might lead to unacceptably low levels of statistical power. Therefore, this result should be verified by large, well-designed epidemiologic population-based studies. Ethnic
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Vitamin D Receptor and Calcium-Sensing Receptor Gene Polymorphisms in Hypercalciuric Stone-Forming Patients

Vitamin D Receptor and Calcium-Sensing Receptor Gene Polymorphisms in Hypercalciuric Stone-Forming Patients

Several studies about common allelic variations in VDR in disorders of calcium metabolism, using Bsm I, Apa I, Taq I and Fok I restriction enzymes have been per- formed, but the results were controversial [12–32] . While some studies disclosed an association between VDR polymorphism and bone mineral density (BMD) [12–15] , others did not [16–19] . Although the link between stone formation and VDR has not yet been clarified, and these polymorphisms do not alter the amino acid sequence of the VDR protein, allelic differences in the 3 ⴕ untranslated region may alter the regulation of messenger RNA stabil- ity and/or translation and thus affect vitamin D activity, or even mediate calcitriol action in the regulation of ex- pression of other target genes involved in renal tubular calcium reabsorption [12, 27, 33] . In addition, even if a specific VDR genotype does not provide evidence for a VDR defect per se, it could be a marker for the disease that could aid in the identification of a possible disease locus [12] . Evaluation of VDR polymorphisms among kidney stone formers, hypercalciuric or not, have shown distinct findings [16, 20–32] . Some investigators found a positive association between polymorphic variations in VDR gene with risk or recurrence of stone formation [27– 29] but other studies were negative [30, 31] . As for urinary calcium, a few studies reported higher calcium excretion related to specific genotypes [21, 24, 32] while others did not [20, 22, 25, 26] .
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Lack of an association between two BER gene polymorphisms and breast cancer risk: a meta-analysis.

Lack of an association between two BER gene polymorphisms and breast cancer risk: a meta-analysis.

Breast cancer is currently the most common cancer and one of the main causes of cancer-related death in the world, which has become a major public health challenge [1]. It is a multifactorial disease caused by complex genetic and environmental factors [2]. Genetic variation in DNA repair genes can cause altered DNA repair function, resulting in accumulation of DNA damage, followed by cell apoptosis or unregulated cell growth and cancer. Individual variations in DNA damage and repair have been associated with breast cancer susceptibility and highlight the importance of DNA damage/repair in the development of the disease. Among DNA repair systems, the base excision repair (BER), which is an important pathway responsible for the repair of base damage and single strand breaks caused by X-rays, oxygen radicals, and alkylating agents, has been associated with risk of cancers [3–6].
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Association of vitamin D receptor BsmI gene polymorphism with risk of tuberculosis: a meta-analysis of 15 studies.

Association of vitamin D receptor BsmI gene polymorphism with risk of tuberculosis: a meta-analysis of 15 studies.

Although a previous meta-analysis conducted by Gao et al suggested the BsmI polymorphism was related to host susceptibil- ity to TB in Asians [16], evidence for overall populations was still insignificant. In our meta-analysis, the number of studies included was almost twice as that reported by Gao et al (15 vs. 9), which can provide enough statistical power to detect modest difference. We first reported that the VDR BsmI gene polymorphism was associated with decreased TB risk in overall populations. Additionally, there are some limitations which need to be addressed. First, although all most control sources were popula- tion-based which might be represent of the general population, we could not obtain enough individual information and a more precise adjusted OR for other covariates such as age, sex and environment factors was not allowed. Secondly, the number of
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Genetic polymorphisms of GSTM1, GSTT1, and GSTP1 with prostate cancer risk: a meta-analysis of 57 studies.

Genetic polymorphisms of GSTM1, GSTT1, and GSTP1 with prostate cancer risk: a meta-analysis of 57 studies.

We used crude ORs with corresponding 95% CIs as a measure of the association between GSTM1, GSTT1 and GSTP1 polymor- phisms and risk of PCa. The significance of the pooled OR was determined by the Z test and P value (two-tailed) ,0.05 was considered significant. In our study, the I 2 test was used to assess the heterogeneity between studies (I 2 ,25% no heterogeneity; I 2 = 25–50% moderate heterogeneity; I 2 .50% large or extreme heterogeneity) [19]. The heterogeneity was considered statistically significant with I 2 .50% or P,0.10. When there was no heterogeneity (I 2 #50% or P$0.10), the fixed-effects model (the Mantel-Haenszel method) was used, otherwise, the random-effects model (the DerSimonian and Laird method) was used when the heterogeneity existed (I 2 .50% or P,0.10) [20,21]. Subgroup analyses were performed by ethnicity, source of controls and gene- gene combinations. In addition, sensitivity analysis was performed by omitting each study in turn to assess the stability of results. To determine the evidence of publication bias, the funnel plot and Egger’s test were both used. An asymmetric plot suggested possible publication bias. For the interpretation of Egger’s test, statistical significance was defined as P,0.05 [22]. All the statistical analyses were performed with MIX statistical software (Version 1.7 for windows).
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