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A meta-analysis of caspase 9 polymorphisms in promoter and exon sequence on cancer susceptibility.

ABSTRACT: BACKGROUND: Caspases are important regulators and executioners in apoptosis pathway and have been defined as either tumor suppressors or oncogenes. Polymorphisms in promoter and exon of caspase 9 were shown to confer genetic susceptibility to multiple cancers, but the results were inconsistent. To accomplish a more precise estimation of the relationship, a meta-analysis was performed. METHODOLOGY/PRINCIPAL FINDINGS: We assessed published studies of the association between caspase 9 polymorphisms and cancer risk from nine studies with 5,528 subjects for rs4645978, six studies with 2,403 subjects for rs105276 and two studies for rs4645981. Overall meta-analysis indicated that no evidence of an association between rs4645978 and cancers was found. Through the stratified analysis, statistically significant reduced cancer risks were observed among Caucasians (AG vs AA: OR?=?0.81, 95% CI?=?0.66-0.99, P(heterogeneity)?=?0.150 and the dominant model: OR?=?0.86, 95% CI?=?0.75-0.99, P(heterogeneity)?=?0.290) and prostate cancer. As for rs105276, Ex5+32G>A polymorphism was found with protective effect in overall meta-analysis (AA vs GG: OR?=?0.75, 95% CI?=?0.60-0.92, P(heterogeneity)?=?0.887; A vs G: OR?=?0.85, 95% CI?=?0.77-0.95, P(heterogeneity)?=?0.739 and the recessive model: OR?=?0.68, 95% CI?=?0.56-0.82, P(heterogeneity)?=?0.309) and Asians group. While for rs4645981, a statistically significant increase in risk of lung cancer was shown in Asians (T vs C: OR?=?1.23, 95% CI?=?1.07-1.42, P(heterogeneity)?=?0.399 and the dominant model: OR?=?1.22, 95% CI?=?1.04-1.43, P(heterogeneity)?=?0.660). CONCLUSIONS/SIGNIFICANCE: Our meta-analysis suggests that the caspase 9 rs4645978 most likely contributes to decreased susceptibility to cancer in Caucasians and prostate cancer. The A allele of rs105276 might be a protective factor for cancer, especially for Asians. However, it seems that rs4645981 confers increased susceptibility to lung cancer in Asians.

SUBMITTER: Xu W

PROVIDER: S-EPMC3355128 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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A meta-analysis of caspase 9 polymorphisms in promoter and exon sequence on cancer susceptibility.

Xu Wei W Jiang Shengqiang S Xu Yuanyuan Y Chen Bo B Li Yan Y Zong Feng F Zhao Weihong W Wu Jianqing J

PloS one 20120517 5

<h4>Background</h4>Caspases are important regulators and executioners in apoptosis pathway and have been defined as either tumor suppressors or oncogenes. Polymorphisms in promoter and exon of caspase 9 were shown to confer genetic susceptibility to multiple cancers, but the results were inconsistent. To accomplish a more precise estimation of the relationship, a meta-analysis was performed.<h4>Methodology/principal findings</h4>We assessed published studies of the association between caspase 9 ...[more]

PMID: 22616010

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Project description:Numerous studies have focused on the association between heme oxygenase-1 (HO-1) gene promoter polymorphisms and susceptibility to cancer; however, results remain ambiguous. The present systematic Human Genome Epidemiology review and meta-analysis aimed to clarify this association. A systematic search was used to assess the association of HO-1 gene polymorphisms with cancer susceptibility in the PubMed, Web of Science, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure databases, with all reviewed studies published before April 10, 2017. Review Manager 5.3 and Stata 12.0 software were used to perform the meta-analysis. A total of 14 studies were included in the analysis. Overall, no significant associations of the HO-1 (GT)n and T(-413)A polymorphisms with cancer susceptibility were identified. However, subgroup analyses by ethnicity and cancer type indicated that the LL and L-allele (LL+LS) genotypes of HO-1 (GT)n were associated with increased susceptibility to cancer compared with the SS+SL and SS genotypes in the following subgroups: East Asian [LL+LS vs. SS: odds ratio (OR)=1.51, 95% confidence interval (CI)=1.11-2.05, P=0.0003; LL vs. SS+SL: OR=1.44, 95% CI=1.04-2.01, P=0.03; LL vs. SS: OR=1.64, 95% CI=1.07-2.52, P=0.02]; squamous cell carcinoma (LL+LS vs. SS: OR=1.78, 95% CI=1.35-2.34, P<0.05; LL vs. SS+SL: OR=1.71, 95% CI=1.34-2.18, P<0.05; LL vs. SS: OR=2.26, 95% CI =1.62-3.14, P<0.05); and digestive tract cancer + East Asian (LL+LS vs. SS: OR=1.56, 95% CI=1.22-1.98, P<0.05; LL vs. SS: OR=1.80, 95% CI=1.06-3.05, P<0.05). These findings indicated that there was no association of the HO-1 (GT)n and T(-413)A polymorphisms with cancer susceptibility, while the L-allele genotypes (LL and LS) of HO-1 (GT)n may be susceptibility factors for cancer in East Asian, digestive tract cancer in East Asian and squamous cell carcinoma populations. Due to limitations of the reviewed studies, additional large-scale and refined studies are now required to confirm the present findings.

Project description:ObjectiveAs an update to other recent meta-analyses, the purpose of this study was to explore whether interleukin-10 (IL-10) polymorphisms and their haplotypes contribute to tuberculosis (TB) susceptibility.MethodsWe searched for published case-control studies examining IL-10 polymorphisms and TB in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Wanfang databases and the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strengths of the associations.ResultsA total of 28 studies comprising 8,242 TB patients and 9,666 controls were included in the present study. There were no significant associations between the -1082G/A, -819C/T, and -592A/C polymorphisms and TB in the pooled samples. Subgroup analyses revealed that the -819T allele was associated with an increased TB risk in Asians in all genetic models (T vs. C: OR=1.17, 95% CI=1.05-1.29, P=0.003; TT vs. CC: OR=1.37, 95% CI=1.09-1.72, P=0.006; CT+TT vs. CC: OR=1.33, 95% CI=1.09-1.63, P=0.006; TT vs. CT+CC: OR=1.17, 95% CI=1.02-1.35, P=0.03) and that the -592A/C polymorphism was significantly associated with TB in Europeans under two genetic models (A vs. C: OR=0.77, 95% CI=0.60-0.98, P=0.03; AA vs. CC: OR=0.53, 95% CI=0.30-0.95, P=0.03). Furthermore, the GCC IL-10 promoter haplotype was associated with an increased risk of TB (GCC vs. others: P=1.42, 95% CI=1.02-1.97, P=0.04). Subgroup analyses based on ethnicity revealed that the GCC haplotype was associated with a higher risk of TB in Europeans, whereas the ACC haplotype was associated with a lower TB risk in both Asians and Europeans.ConclusionsThis meta-analysis suggests that the IL-10-819T/C polymorphism is associated with the risk of TB in Asians and that the IL-10-592A/C polymorphism may be a risk factor for TB in Europeans. Furthermore, these data indicate that IL-10 promoter haplotypes play a vital role in the susceptibility to or protection against the development of TB.

Project description:BackgroundStudies investigating the association between single-nucleotide polymorphisms (SNPs) of the cytochrome P450 1B1 (CYP1B1) and prostate cancer (PCa) risk report conflicting results. To derive a more precise estimation of the relationship between CYP1B1 polymorphisms and PCa risk, a meta-analysis was performed.Methodology/principal findingsA comprehensive literature search was conducted to identify all eligible studies of CYP1B1 polymorphisms and PCa risk. A total of 14 independent studies, including 6380 cases and 5807 controls, were identified. We investigated by meta-analysis the effects of 5 polymorphisms in CYP1B1 L432V (12 studies, 5999 cases, 5438 controls), R48G (6 studies, 1647 cases, 1846 controls), N453S (4 studies, 1407 cases, 1499 controls), -13C/T (4 studies, 1116 cases, 1114 controls), and A119S (4 studies, 1057 cases, 1018 controls). There was no evidence that L432V had significant association with PCa in overall population. After subgroup analyses by ethnicity, we found that L432V was significantly associated with PCa risk in Asians (additive: OR?=?2.38, 95%CI?=?1.31-4.33, P?=?0.004; recessive: OR?=?2.11, 95%CI?=?1.17-3.79, P?=?0.01; dominant: OR?=?1.52, 95%CI?=?1.14-2.01, P?=?0.004; allelic: OR?=?1.52, 95%CI?=?1.20-1.92, P?=?0.0006). When stratified by source of controls, significantly elevated PCa risk was found in all genetic models in population based studies (additive: OR?=?1.34, 95%CI?=?1.14-1.57, P?=?0.0003; recessive: OR?=?1.25, 95%CI?=?1.09-1.43, P?=?0.002; dominant: OR?=?1.25, 95%CI?=?1.11-1.41, P?=?0.0002; allelic: OR?=?1.18, 95%CI?=?1.09-1.28, P<0.0001). For N453S, there was a significant association between N453S polymorphism and PCa risk in both overall population (dominant: OR?=?1.18, 95%CI?=?1.00-1.38, P?=?0.04) and mixed population (domiant: OR?=?1.31, 95%CI?=?1.06-1.63, P?=?0.01; allelic: OR?=?1.27, 95%CI?=?1.05-1.54, P?=?0.01). For A119S, our analysis suggested that A119S was associated with PCa risk under recessive model in overall population (OR?=?1.37, 95%CI?=?1.04-1.80, P?=?0.03).ConclusionsThe results suggest that L432V, N453S, and A119S polymorphisms of CYP1B1 might be associated with the susceptibility of PCa. Further larger and well-designed multicenter studies are warranted to validate these findings.

Dataset Information

A meta-analysis of caspase 9 polymorphisms in promoter and exon sequence on cancer susceptibility.

Publications

A meta-analysis of caspase 9 polymorphisms in promoter and exon sequence on cancer susceptibility.

Similar Datasets

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