Recessive Comparison Research Articles

Cyclin D1 (CCND1) G870A polymorphisms and cervical cancer susceptibility: a meta-analysis based on ten case-control studies.

Many studies have evaluated the association between cyclin D1 (CCND1) G870A polymorphism and cervical cancer susceptibility. However, these studies showed inconsistent results. The aim of this study was to derive a more precise estimation of this association. We searched PubMed and Embase for related studies that had been published in English, and ten case-control studies with a total of 2,864 cases and 3,898 controls were finally identified to be eligible studies in the meta-analysis. The association was assessed by summarizing the odds ratios (ORs) with the corresponding 95 % confidence intervals (CIs). Overall, there was no significant association between cyclin D1 (CCND1) G870A polymorphism and cervical cancer risk (for the allele model A vs. G: OR = 1.02, 95 % CI 0.88-1.19, p = 0.76; for the co-dominant model AA vs. GG: OR = 1.03, 95 % CI 0.75-1.41, p = 0.85; for the dominant model AA + GA vs. GG: OR = 1.00, 95 % CI 0.78-1.28, p = 0.99; for the recessive comparison AA vs. GA + GG: OR = 1.06, 95 % CI 0.85-1.32, p = 0.62). In subgroup analysis by ethnicity, no significant difference was found in both Asians and Caucasians. In summary, the present meta-analysis provides evidence that genotypes for the cyclin D1 (CCND1) G870A polymorphism may be not associated with genetic susceptibility of cervical cancer.

Genetic polymorphisms of RAD51 and XRCC3 and acute myeloid leukemia risk: a meta-analysis

Studies on gene polymorphisms of RAD51 and X-ray repair cross-complementing group 3 (XRCC3) and acute myeloid leukemia risk (AML) are conflicting and there is no recent meta-analysis. Therefore, the purpose of this study was to evaluate the effect of RAD51 G135C and XRCC3 Thr241Met genotypes on AML susceptibility. We conducted a systematic search of three databases including PubMed and EMBASE for the period up to 20 February 2013 and identified 43 relevant studies. Six eligible studies were eventually selected for RAD51 (1764 cases and 3469 controls) and six studies for XRCC3 (1352 cases and 2582 controls). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of AML associated with RAD51 and XRCC3 were appropriately calculated based on fixed- or random-effects models. The quality of studies was evaluated using the Newcastle-Ottawa Scale (NOS). Subgroup analyses were performed among Asian, Caucasian and other populations. The pooled results showed that the leukemia risk was not significantly associated with RAD51: the same results were obtained among any subgroup analysis. No significant association was demonstrated for AML risk with XRCC3 in the total population, but elevated associations were observed in Caucasians for the homozygote and recessive comparison (Met/Met vs. Thr/Thr, OR = 1.67, 95% CI = 1.09–2.57, p = 0.019; recessive model, OR = 1.78, 95% CI = 1.19–2.65, p = 0.005). This meta-analysis provides evidence that the RAD51 and XRCC3 polymorphisms are not associated with an increased risk of AML in the total population.

3R Variant of Thymidylate Synthase 5'-untranslated Enhanced Region Contributes to Colorectal Cancer Risk: A Meta-analysis

Studies investigating the association of 2R/3R polymorphism in the thymidylate synthase 5'-untranslated enhanced region (TSER) and colorectal cancer (CRC) risk have reported conflicting results. Thus, a meta-analysis was performed to summarize the data on the potential association. Pubmed, Embase and CBM databases were searched for all available studies. Links between the TSER 2R/3R polymorphism and CRC risk were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). Seven case-control studies with a total of 2723 cases and 4030 controls were included in this meta-analysis. The results showed that the 3R variant of TSER 2R/3R polymorphism contributes to CRC risk in two comparison models (OR 3R vs. 2R =1.10, 95%CI 1.02-1.18, P = 0.015; OR Homozygote comparison model = 1.22 1.04-1.43, 95%CI 1.04- 1.43, P = 0.012). Subgroup analyses by ethnicity further demonstrated a contribution in Caucasians with three comparison models (OR 3R vs. 2R = 1.10, 95%CI 1.02-1.19, P = 0.015; OR Homozygote comparison model = 1.21, 95%CI 1.03-1.41, P = 0.019; OR Recessive comparison model = 1.18, 95%CI 1.05-1.33, P = 0.008). However, the association in the Asian population was still uncertain due to the limited data (all P values were more than 0.05). Our meta-analysis suggests that the 3R variant of Thymidylate synthase 5'-untranslated enhanced region 2R/3R polymorphism contributes to gastric cancer risk in the Caucasian population, while any association in Asian populations needs further study.

Association between α1-antichymotrypsin signal peptide −15A/T polymorphism and the risk of Alzheimer’s disease: a meta-analysis

No consensus has been recently reached at the relationship between the α1-antichymotrypsin (ACT) signal peptide -15A/T polymorphism and Alzheimer’s disease (AD) risk. Thus, our study aimed to better assess this association by performing a meta-analysis, including 4,212 cases and 4,039 controls from 29 studies. Odds ratios (ORs) with the 95% confidence interval (CI) were used to assess the strength of relationship between ACT -15A/T polymorphism and AD risk. Overall, a borderline statistically significant association was detected under recessive model comparison in all subjects (AA vs. AT+TT: OR 1.12, 95% CI 1.01-1.25, P = 0.04). But in subgroup analysis by ethnicity, no significant association was found in Caucasians, Asians, or Africans. Moreover, after exclusion of one study which affect the heterogeneity, the ACT A allele and AA genotype were statistically associated with late-onset AD (LOAD) risk (AA vs. TT: OR 1.25, 95% CI 1.06-1.48, P = 0.007, A vs. T: OR 1.12, 95% CI 1.03-1.21, P = 0.008), especially in Caucasians. In conclusion, our study suggests that the common α1-antichymotrypsin signal peptide -15A/T polymorphism may not be a major risk factor for AD. However, the polymorphism is capable of increasing LOAD risk.

Nucleotide excision repair gene ERCC1 polymorphisms contribute to cancer susceptibility: a meta-analysis

Individual studies of the associations between excision repair cross-complimentary group 1 (ERCC1) polymorphisms and cancer susceptibility have shown inconclusive results. To derive a more precise estimation of the relationship between three well-characterised polymorphisms on ERCC1 and the risk of cancer, we performed a meta-analysis based on 48 publications. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the associations. We found that ERCC1 17677A (rs3212961) variant genotypes were associated with significantly increased overall risk of cancer without substantial heterogeneity (AA versus CC, OR = 1.36, 95% CIs: 1.10-1.68; AC versus CC: OR = 1.11, 95% CIs: 0.99-1.26; dominant comparison: AA/AC versus CC: OR = 1.15, 95% CIs: 1.02-1.29; recessive comparison: AA versus AC/CC: OR = 1.25, 95% CIs: 1.05-1.49). The ERCC1 19007 C (rs11615) allele had null effects on overall risk of cancer; but in the stratified analyses, we observed an elevated association in Asian populations with homozygote variants and hospital-based controls. In addition, during further stratified analyses of cancer groups, homozygote variants were found that are associated with lung cancer and smoking-related cancers. Also, the observed ERCC1 19007 C heterozygote variant contributes to the development of skin cancer. However, the ERCC1 8092C > A (rs3212986) polymorphism did not appear to have an effect on cancer risk. Additionally, no evidence of publication bias was observed in these polymorphisms. Our meta-analysis supports the conclusion that the ERCC1 17677A > C and ERCC1 19007T > C polymorphisms, but not the ERCC1 8092C > A polymorphism, are low-penetrance risk factors for cancer development.

Association between the TPH1 A218C polymorphism and risk of mood disorders and alcohol dependence: Evidence from the current studies

Several studies have assessed the association between genetic polymorphisms of tryptophan hydroxylase (TPH1) and risk of mood disorders and alcohol dependence, with controversial results. Our aim was to assess the association of TPH1 A218C polymorphism (rs1800532) with mood disorders, including major depressive disorder and bipolar disorder, and alcohol dependence by using meta-analysis. Data were collected from the related literatures published until November 25, 2010 from MEDLINE, EMBASE and ISI Web of Science databases, and meta-analysis stratified by ethnicity was performed in either fixed or random effect model as appropriate by using Stata Statistical Package (version 10.0). Twenty-seven individual studies were included in the current study, among which, there were 9 studies for bipolar disorder, with 1951 cases and 2161 controls, 14 studies for major depressive disorder, with 2340 cases and 3204 controls, and 4 studies for alcohol dependence, with 601 cases and 711 controls. We found that in Caucasian population, the TPH1 218AA genotype was significantly associated with increased bipolar disorder risk (recessive comparison: OR, 1.42; Bonferroni-adjusted P=0.006; homozygote comparison: OR, 1.63; Bonferroni-adjusted P=0.072), and elevated alcohol dependence risk (recessive comparison: OR, 1.83; Bonferroni-adjusted P=0.012), while the association was not significant in Asian population. Moreover, the A218C polymorphism did not appear to have any effect on major depressive disorder risk either in Caucasians or in Asians. The TPH1 A218C polymorphism is a potential biomarker for bipolar disorder and alcohol dependence risk in Caucasian population.

RAD51 135G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies

Growing evidence suggests that RAD51 plays a pivotal role in the repair of DNA double-strand breaks and the maintenance of genomic stability. A single nucleotide polymorphism, 135G/C, has been identified in the 5' untranslated region of the RAD51 gene and has been shown to influence gene transcription activity. Previous studies yielded conflicting results as to the association of 135G/C polymorphism with breast cancer. We aimed to assess the effect of 135G/C of RAD51 on breast cancer susceptibility with the use of a meta-analysis. We performed a meta-analysis of 21 published case-control studies up to April 2010. We found that the CC genotype was associated with a significantly increased risk of breast cancer when compared with the GG, CG, and CG/GG genotypes. Subgroup analyses showed that individuals carrying the CC genotype were associated with an elevated tumor risk in European populations and in sporadic breast cancer. After stratified analyses according to manuscript quality, the CC genotype was associated with a significantly increased risk of breast cancer compared with the CG genotype in studies of both higher and lower quality. However, significantly elevated risk was found in studies of higher quality, but not in studies of lower quality when homozygote and a recessive comparison model were tested. This meta-analysis indicates that RAD51 135G/C polymorphism may be identified as a susceptibility locus for breast cancer.

CASP8 polymorphisms contribute to cancer susceptibility: evidence from a meta-analysis of 23 publications with 55 individual studies

Several potentially functional polymorphisms of CASP8 encoding an apoptotic enzyme, caspase 8, have been implicated in cancer risk, but individually published studies showed inconclusive results. We performed a meta-analysis of 23 publications with a total of 55 174 cancer cases and 59 336 controls from 55 individual studies. We summarized the data on the associations between three studied CASP8 polymorphisms (G>C D302H, -652 6N del and Ex14-271A>T) and cancer risk and performed subgroup analysis by ethnicity, cancer type, study design and etiology. We found that D302H CC and CG variant genotypes were associated with significantly reduced overall risk of cancers using conservative random genetic models [homozygote comparison: odds ratios (OR) = 0.79; 95% confidence interval (CI): 0.69-0.92; dominant comparison: OR = 0.93, 95% CI: 0.89-0.98; recessive comparison: OR = 0.81, 95% CI: 0.71-0.93). In further stratified analyses, the reduced cancer risk remained for subgroups of Caucasians, breast or estrogen-related cancers, and hospital- or population-based studies, except for an elevated risk for brain tumors. Similarly, the -652 6N del polymorphism was also associated with significantly reduced overall risk of cancers (homozygote comparison: OR = 0.84, 95% CI: 0.75-0.94; dominant comparison: OR = 0.88, 95% CI: 0.81-0.96; recessive comparison: OR = 0.90, 95% CI: 0.82-0.99) and all subgroups analyzed. However, the Ex14-271A>T polymorphism did not appear to have an effect on cancer risk. These results suggest that CASP8 D302H and -652 6N del polymorphisms are potential biomarkers for cancer risk.