Arsenic-induced health effects and genetic damage in keratotic individuals: involvement of p53 arginine variant and chromosomal aberrations in arsenic susceptibility

In West Bengal, India, more than 6 million people are exposed to arsenic through drinking water. Chronic arsenic exposure results in several multisystemic non-cancerous as well as cancerous effects in humans. Among non-cancerous effects, arsenic-specific skin lesions, conjunctivitis, peripheral neuropathy and respiratory diseases are prominent. One of the major consequences of chronic arsenic exposure is keratosis, the precancerous state of skin cancer. The tumor suppressor protein p53 consists of a polymorphism proline72arginine reported to be associated with various types of cancers. Previously we have reported that the p53 codon 72 arginine (Arg) homozygous genotype is associated with the development of arsenic-induced keratosis. In the present study we have investigated the distribution of health effects and chromosomal aberrations (CAs) in the individuals with keratosis. We have compared individuals with keratosis with those without arsenic-induced skin lesions but drinking similar level of arsenic-contaminated water. Attempts have also been made to find out the association of the p53 risk genotype with health effects and chromosomal aberrations. This study comprises of 349 unrelated exposed individuals (162 individuals with keratosis and 187 individuals without arsenic-specific skin lesions) from highly arsenic-affected districts of West Bengal, India. The results showed that health effects (i.e. peripheral neuropathy, conjunctivitis and respiratory illness) and chromosomal aberrations were significantly higher in the keratotic group compared to individuals with no skin lesions. Moreover, individuals with the arginine homozygous genotype showed increased levels of chromosomal aberrations compared to individuals with other genotypes; however, we did not find any significant association of the risk genotype with health effects. This study suggests that individuals with keratosis are more susceptible to arsenic-induced health effects and genetic damage and that the arginine variant of p53 can further influence the repair capacity of arsenic-exposed individuals, leading to increased accumulation of chromosomal aberrations.     

Variation in DNA repair gene XRCC3 affects susceptibility to astrocytomas and glioblastomas

The gene XRCC3 (X-ray cross complementing group 3) has the task of repairing damage that occurs when there is recombination between homologous chromosomes. Repair of recombination between homologous chromosomes plays an important role in maintaining genome integrity, although it is known that double-strand breaks are the main inducers of chromosomal aberrations. Changes in the XRCC3 protein lead to an increase in errors in chromosome segregation due to defects in centrosomes, resulting in aneuploidy and other chromosomal aberrations, such as small increases in telomeres. We examined XRCC3 Thr241Met polymorphism using PCR-RFLP in 80 astrocytoma and glioblastoma samples. The individuals of the control group (N = 100) were selected from the general population of the S?o Paulo State. Odds ratio and 95%CI were calculated using a logistic regression model. Patients who had the allele Met of the XRCC3 Thr241Met polymorphism had a significantly increased risk of tumor development (odds ratio = 3.13; 95% confidence interval = 1.50-6.50). There were no significant differences in overall survival of patients. We suggest that XRCC3 Thr241Met polymorphism is involved in susceptibility for developing astrocytomas and glioblastomas.     

A Strong Relationship Between Oral Squamous Cell Carcinoma and DNA Repair Genes

Single nucleotide polymorphisms of DNA repair genes alter protein function and modulate DNA repair efficiency in various cancers. The X-ray repair cross-complementing group (XRCC) is responsible for the repair of DNA base damage and single-strand breaks. The aim of our study was to investigate the association of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms with the susceptibility to develop oral squamous cell carcinoma (OSCC) in Turkish subjects. One hundred eleven patients with OSCC and 148 healthy controls were recruited for the study. Genetic analysis was performed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). We found that the XRCC1 Arg399Gln Gln/Gln genotype and Gln allele were risk factors for OSCC. Also, Arg/Arg genotype and Arg allele had protective effects against OSCC. Relative to XRCC3 Thr241Met polymorphism, carrying homozygote variants (Thr/Thr and Met/Met) was related with elevated OSCC risk. However, the heterozygote genotype and Thr allele variants were shown to be protective against OSCC. We suggest that XRCC1 Arg399Gln Gln/Gln genotype, Gln allele, and homozygote variants of XRCC3 Thr241Met polymorphism may be a risk factor for predisposition of OSCC in Turkish. In addition, XRCC3 Thr241Met genotype could be associated with tumor size and level of daily smoking.     

Association between the XRCC3 T241M polymorphism and risk of cancer: Evidence from 157 case–control studies

The T241M polymorphism in the X-ray cross-complementing group 3 (XRCC3) had been implicated in cancer susceptibility. The previous published data on the association between XRCC3 T241M polymorphism and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and XRCC3 T241M (61,861 cases and 84,584 controls from 157 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ration [OR] = 1.07, 95% confidence interval [CI] = 1.00–1.13; recessive model: OR = 1.15, 95% CI = 1.08–1.23; additive model: OR = 1.17, 95% CI = 1.08–1.28) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of bladder cancer and breast cancer, especially in Caucasians. In addition, significantly decreased lung cancer risk was also observed. In summary, this meta-analysis suggests the participation of XRCC3 T241M in the susceptibility for bladder cancer and breast cancer, especially in Caucasians, and XRCC3 T241M polymorphism is associated with decreased lung cancer risk. Moreover, our work also points out the importance of new studies for T241M association in some cancer types, such as gastric cancer, colorectal cancer, and melanoma skin cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC3 polymorphism in cancer development.     

Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis

The X-ray repair cross-complementing group 3 (XRCC3) protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539) polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31–3.01, P = 0.001). A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97–1.68, P = 0.08). In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49–3.89, p = 0.0003) and breast irradiation (OR = 1.41, 95%CI: 1.02–1.95, p = 0.04), whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26–0.86, P = 0.01). Well-designed large-scale clinical studies are required to further validate our results.     

MLH1 and XRCC1 polymorphisms in Mexican patients with colorectal cancer

DNA repair proteins maintain DNA integrity; polymorphisms in genes coding for these proteins can increase susceptibility to colorectal cancer (CRC) development. We analyzed a possible association of MLH1 -93G>A and 655A>G and XRCC1 Arg194Trp and Arg399Gln polymorphisms with CRC in Mexican patients. Genomic DNA samples were obtained from peripheral blood of 108 individuals with CRC (study group) at diagnosis and 120 blood donors (control group) from Western Mexico; both groups were mestizos. The polymorphisms were detected by PCR-RFLP. Association was estimated by calculating the odds ratio (OR). We found that the MLH1 and XRCC1 polymorphisms were in Hardy- Weinberg equilibrium. The MLH1 655A>G polymorphism in the 655G allele was associated with a 2-fold increase risk for CRC (OR = 2.04 and 95% confidence interval (95%CI) = 1.12-3.69; P < 0.01), while the MLH1 -93G>A polymorphism allele was associated with a protective effect (OR = 0.60, 95%CI = 0.40-0.89; P = 0.01 in the -93A allele and OR = 0.32, 95%CI = 0.13-0.79; P = 0.01 in the AA genotype). The XRCC1 Arg194Trp and Arg399Gln polymorphisms did not show any significant associations. In conclusion, we found that MLH1 -93G>A and 655A>G polymorphisms are associated with CRC in Mexican patients.     

Association between the XRCC3 polymorphisms and breast cancer risk: meta-analysis based on case–control studies

The previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) T241M, A4541G, and A17893G polymorphisms and breast cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between breast cancer and XRCC3 T241M (21,910 cases and 23,961 controls), A4541G (9,633 cases and 10,994 controls), and A17893G polymorphisms (10,761 cases and 12,235 controls) in different inheritance models. When all the eligible studies were pooled into the meta-analysis of XRCC3 T241M polymorphism, significantly increased risk of breast cancer was observed in recessive model (odds' ratio [OR] = 1.10, 95% confidence interval [CI] = 1.04–1.16) and in additive model (OR = 1.10, 95% CI = 1.03–1.16). No significant association was found between A4541G polymorphism and breast cancer risk. When all the eligible studies were pooled into the meta-analysis of XRCC3 A17893G polymorphism, no significant association was found in any genetic model. Additionally, when one study was deleted in the sensitive analysis, the results of XRCC3 A17893G were changed in the additive model (OR = 0.90, 95% CI = 0.82–0.99) and dominant model (OR = 0.94, 95% CI = 0.89–0.99). In summary, this meta-analysis indicates that T241M polymorphism show an increased breast cancer risk and A17893G polymorphism may be associated with decreased breast cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on XRCC3 T241M, A4541G, and A17893G polymorphisms and breast cancer risk.     

The XRCC3 Thr241Met polymorphism and breast cancer risk: a case–control study in a Thai population

The X-ray repair cross-complementing group 3 gene (XRCC3) belongs to a family of genes responsible for repairing DNA double-strand breaks caused by normal metabolic processes and exposure to ionizing radiation. Polymorphisms in DNA repair genes may alter an individual's capacity to repair damaged DNA and may lead to genetic instability and contribute to malignant transformation. We examined the role of a polymorphism in the XRCC3 gene (rs861529; codon 241: threonine to methionine change) in determining breast cancer risk in Thai women. The study population consisted of 507 breast cancer cases and 425 healthy women. The polymorphism was analysed by fluorescence-based melting curve analysis. The XRCC3 241Met allele was found to be uncommon in the Thai population (frequency 0.07 among cases and 0.05 among controls). Odds ratios (OR) adjusted for age, body mass index, age at menarche, family history of breast cancer, menopausal status, reproduction parameters, use of contraceptives, tobacco smoking, involuntary tobacco smoking, alcohol drinking, and education were calculated for the entire population as well as for pre- and postmenopausal women. There was a significant association between 241Met carrier status and breast cancer risk (OR 1.58, 95% confidence interval (CI) 1.02–2.44). Among postmenopausal women, a slightly higher OR (1.82, 95% CI 0.95–3.51) was found than among premenopausal women (OR 1.48, 95% CI 0.82–2.69). Our findings suggest that the XRCC3 Thr241Met polymorphism is likely to play a modifying role in the individual susceptibility to breast cancer among Thai women as already shown for women of European ancestry.     

XRCC3 Thr241Met Is Associated with Response to Platinum-Based Chemotherapy but Not Survival in Advanced Non-Small Cell Lung Cancer

Background

A lot of studies have investigated the correlation between x-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and clinical outcomes in non-small cell cancer (NSCLC), while the conclusion is still conflicting.

Materials and Methods

We conducted this meta-analysis to evaluate the predictive value of XRCC3 Thr241Met polymorphism on response and overall survival of patients with NSCLC. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were used to estimate the association strength.

Results

A total of 14 eligible studies with 2828 patients were identified according to our inclusion criteria. Meta-analysis results showed that carriers of the variant 241Met allele were significantly associated with good response, compared with those harboring the wild 241Thr allele (Met vs. Thr, OR = 1.453, 95% CI: 1.116–1.892, P_{heterogeneity} = 0.968 and ThrMet+MetMet vs. ThrThr, OR = 1.476, 95% CI: 1.087–2.004, P_{heterogeneity} = 0.696). This significant association was observed in Caucasian population but not in Asian population. On the other hand, there was no significant association of XRCC3 Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95% CI: 0.929–1.261, P_{heterogeneity} = 0.564), and there was no difference between Asian and Caucasian population.

Conclusions

These findings suggest a predictive role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy in patients with advanced NSCLC. Additionally, we first report that the XRCC3 Thr241Met polymorphism is associated with response to platinum-based chemotherapy and highlights the prognostic value of the XRCC3 Thr241Met polymorphism.     

XRCC3 Thr241Met Polymorphism and Clinical Outcomes of NSCLC Patients Receiving Platinum-Based Chemotherapy: A Systematic Review and Meta-Analysis

Introduction

X-ray repair cross-complementing protein 3 (XRCC3) is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy.

Methods

A systematic review and meta-analysis was performed to evaluate the predictive value of XRCC3 Thr241Met polymorphism on clinical outcomes of advanced NSCLC receiving platinum-based chemotherapy. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were analyzed.

Results

A number of 11 eligible studies were identified according to the inclusion criteria. Carriers of the variant XRCC3 241Met allele were significantly associated with good response to platinum-based chemotherapy (ThrMet/MetMet vs. ThrThr: OR  = 1.509, 95% CI: 1.099–2.072, P_{heterogeneity}  = 0.618). The XRCC3 Thr241Met polymorphism was not associated with OS (MetMet vs. ThrThr, HR  = 0.939, 95% CI:0.651–1.356, P_{heterogeneity}  = 0.112) or PFS (MetMet vs. ThrThr, HR  = 0.960, 95% CI: 0.539–1.710, P_{heterogeneity}  = 0.198). Additionally, no evidence of publication bias was observed.

Conclusions

This systematic review and meta-analysis shows that carriers of the XRCC3 241Met allele are associated with good response to platinum-based chemotherapy in advanced NSCLC, while the XRCC3 Thr241Met polymorphism is not associated with OS or PFS.     

Polymorphisms in <Emphasis Type="Italic">RAD51, XRCC2</Emphasis> and <Emphasis Type="Italic">XRCC3</Emphasis> genes of the homologous recombination repair in colorectal cancer—a case control study

XRCC2 and XRCC3 proteins are structurally and functionally related to RAD51 which play an important role in the homologous recombination, the process frequently involved in cancer transformation. In our previous work we show that the 135G>C polymorphism (rs1801320) of the RAD51 gene can modify the effect of the Thr241Met polymorphism (rs861539) of the XRCC3 gene. We tested the association between the 135G>C polymorphism of the RAD51 gene, the Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism (rs3218536) of the XRCC2 gene and colorectal cancer risk and clinicopathological parameters. Polymorphisms were evaluated by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) in 100 patients with invasive adenocarcinoma of the colon and in 100 sex, age and ethnicity matched cancer–free controls. We stratified the patients by genotypes, tumour Duke’s and TNM stage and calculated the linkage of each genotype with each stratum. Carriers of Arg188Arg/Me241tMet, His188His/Thr241Thr and His188His/G135G genotypes had an increased risk of colorectal cancer occurrence (OR 5.70, 95% CI 1.10–29.5; OR 12.4, 95% CI 1.63–94.9; OR 5.88, 95% CI 1.21–28.5, respectively). The C135C genotype decreased the risk of colorectal cancer singly (OR 0.06, 95% CI 0.02–0.22) as well as in combination with other two polymorphisms. TNM and Duke’s staging were not related to any of these polymorphisms. Our results suggest that the 135G>C polymorphism of the RAD51 gene can be an independent marker of colorectal cancer risk. The Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism of the XRCC2 gene can modify the risk of colorectal cancer.     

Genetic polymorphisms of the DNA repair gene and risk of nasopharyngeal carcinoma

Context: X-ray repair cross-complementing groups 1 and 3 (XRCC1 and XRCC3) and xeroderma pigmentosum group D (XPD) are mainly involved in base excision repair, homologous recombination repair, and nucleotide excision repair of DNA repair pathways, respectively. Previous studies have demonstrated that their gene polymorphisms were associated with some cancer susceptibility. Objective and design: To investigate the effect of XPD Lys751Gln, XRCC1 Arg399Gln, Arg194Trp, Arg280His, and XRCC3 Thr241Met polymorphisms on the risk of nasopharyngeal carcinoma (NPC), a population-based case-control study of 153 NPC patients and 168 healthy controls among Sichuan population was conducted. Results: Our results showed that XRCC1 codon 194 Trp allele was associated with an increased risk of NPC (odds ratio [OR] = 1.828, 95% confidence interval [CI]: 1.286-2.598), and XPD codon 751Gln allele was associated with a borderline decrease of NPC (OR = 0.600, 95% CI: 0.361-1.000); combination analysis showed that individuals with both putative genotypes of XPD codon 751 Lys/Lys and XRCC1 codon 194 Arg/Trp or Trp/Trp have a significantly elevated risk of NPC (OR = 2.708, 95% CI: 1.338-5.478). Conclusion: The results indicated that XRCC1 codon 194 Trp allele and XPD codon 751 Lys allele may be contributing factors in the risk of NPC.     

The polymorphism of DNA repair genes XRCC1, XRCC3 and the level of chromosomal aberrations in the Uranium workers

Association between the polymorphism of DNA repair genes XRCC1 Arg399ln and XRCC3 Thr241Met and the frequency of chromosomal aberrations in the uranium workers was studied. The Gln/Gln genotype of gene XRCC1 was associated with a significant increase in the number of chromosomal aberrations as compared to the corresponding homozygous wild type Arg/Arg (p < 0.05). The frequency of chromosomal aberrations in heterozygous carriers of the XRCC3gene Thr/Met was lower than in the homozygous carriers of the wild type Thr/Thr (p < 0.001).     

Interleukin-10 gene polymorphisms and chronic/aggressive periodontitis susceptibility: A meta-analysis based on 14 case-control studies

Interleukin-10 (IL-10) has been described as an anti-inflammatory cytokine and IL-10 gene polymorphisms was associated with altered interleukin-10 levels, therefore, we aimed to conduct a meta-analysis assessing the association of IL-10 genetic polymorphisms with the risk of both chronic periodontitis (CP) and aggressive periodontitis (AgP). Electronic databases were acquired from PubMed, Embase, the Sinomed and WANFANG. Fourteen studies with 1438 patients and 1303 control subjects investigated the association of the three single-nucleotide polymorphisms (SNPs) of IL-10 (-1082A>G, -819C>T, -592C>A) and chronic/aggressive periodontitis risk were brought into this study. We found that there was no association between IL-10 -1082 gene polymorphism and periodontitis risk (either CP or AgP), even when we separately investigated sub-group analysis among Caucasians. The -819 polymorphism seemed to be a genetic risk factor to CP among Caucasians (T allele vs. C allele: OR=1.55, 95%CI=1.07-2.24; CT vs. CC: OR=1.64, 95%CI=1.00-2.67). When excluding one study deviated from HWE, the results showed that the T allele carriers had a significantly risk of CP in overall population (T allele vs. C allele: OR=1.23, 95%CI=1.03-1.48). Furthermore, the results of this meta-analysis showed that -592 polymorphism was associated with a significantly increased risk of CP (A allele vs. C allele: OR=1.38, 95%CI=1.04-1.85; AA vs. CA+CC: OR=1.39, 95%CI=1.05-1.85 for overall analysis; A allele vs. C allele: OR=1.97, 95%CI=1.36-3.86; AA vs. CC: OR=3.70, 95%CI=1.32-10.39; CA vs. CC: OR=2.22, 95%CI=1.36-3.64, AA+CA vs. CC: OR=2.35, 95%CI=1.46-3.79 for Caucasian descent analysis). This meta-analysis suggested that IL-10 -819 and -592 gene polymorphisms were associated with CP, especially among Caucasians. Further research is needed to assess possible gene-gene or gene-environment-lifestyle interactions on periodontal disease..     

The BARD1 Cys557Ser variant and risk of familial breast cancer in a South-American population

Since the discovery of the BRCA1 and BRCA2 genes, much work has been carried out to identify further breast cancer (BC) susceptibility genes. BARD1 (BRCA1-associated ring domain) was originally identified as a BRCA1-interacting protein but has also been described in tumor-suppressive functions independent of BRCA1. Some association studies have suggested that the BARD1 Cys557Ser variant might be associated with increased risk of BC, but others have failed to confirm this finding. To date, this variant has not been analyzed in Spanish or South-American populations. In this study, using a case-control design, we analyzed the C-terminal Cys557Ser change in 322 Chilean BC cases with no mutations in BRCA1 or BRCA2 and in 570 controls in order to evaluate its possible association with BC susceptibility. BARD1 Cys557Ser was associated with an increased BC risk (P = 0.04, OR = 3.4 [95 % CI 1.2-10.2]) among cases belonging to families with a strong family history of BC. No difference between single cases affected with age <50 years at diagnosis (n = 117) and controls was observed for carriers of Cys/Ser genotype. It is likely that this variant is not involved in BC risk in this group of women. We also analyzed a possible interaction between BARD1 557Ser/XRCC3 241Met variants considering the role of both genes in the maintenance of genome integrity. The combined genotype Cys/Ser-carrier with the XRCC3 241Met allele was associated with an increased BC risk (P = 0.02, OR = 5.01 [95 % CI 1.36-18.5]) among women belonging to families with at least three BC and/or ovarian cancer cases. Our results suggest that BARD1 557Ser and XRCC3 241Met may play roles in BC risk in women with a strong family history of BC. Nevertheless there is no evidence of an interaction between the two SNPs. These findings should be confirmed by other studies and in other populations.     

DNA repair genes XRCC1 and XRCC3 polymorphisms and their relationship with the level of micronuclei in breast cancer patients

Breast cancer (BC) is the most prevalent type worldwide, besides being one of the most common causes of death among women. It has been suggested that sporadic BC is most likely caused by low-penetrance genes, including those involved in DNA repair mechanisms. Furthermore, the accumulation of DNA damage may contribute to breast carcinogenesis. In the present study, the relationship between two DNA repair genes, viz., XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms, and the levels of chromosome damage detected in 65 untreated BC women and 85 healthy controls, was investigated. Chromosome damage was evaluated through micronucleus assaying, and genotypes determined by PCR-RFLP methodology. The results showed no alteration in the risk of BC and DNA damage brought about by either XRCC1 (Arg399Gln) or XRCC3 (Thr241Met) action in either of the two groups. Nevertheless, on evaluating BC risk in women presenting levels of chromosome damage above the mean, the XRCC3Thr241Met polymorphism was found to be more frequent in the BC group than in the control, thereby leading to the conclusion that there is a slight association between XRCC3 (241 C/T) genotypes and BC risk in the subgroups with higher levels of chromosome damage.     

Association of -619C/T polymorphism in CDSN gene and psoriasis risk: a meta-analysis

Previous studies investigating the association between corneodesmosin (CDSN) polymorphisms and psoriasis risk have provided inconsistent results. The aim of our study was to clarify the effects of CDSN -619C/T polymorphism on psoriasis risk by conducting a meta-analysis. We conducted searches of the published literature in Pubmed and Embase databases up to October 2010. Six studies with a total of 842 psoriasis cases and 981 healthy controls were retrieved. Statistical analysis was performed with the programs Review Manager (version 5.0.24) and Stata (version 9.2). Meta-analysis results showed that there was no significant difference in CDSN -619C/T genotype distribution between psoriasis and control in the comparisons of C allele vs T allele, CC vs CT + TT, CC + CT vs TT, CC vs TT, and CC vs CT (respectively: OR = 1.28, 95%CI = 0.82-2.00, P = 0.28; OR = 1.33, 95%CI = 0.80-2.21, P = 0.28; OR = 1.23, 95%CI = 0.80-1.91, P = 0.35; OR = 1.41, 95%CI = 0.64-3.12, P = 0.40; OR = 1.30, 95%CI = 0.81-2.06, P = 0.27). In the subgroup analysis by ethnicity, results also showed no significant association between CDSN -619C/T polymorphism and susceptibility to psoriasis in both Caucasian and Asian populations. In conclusion, this meta-analysis suggests that CDSN -619C/T polymorphism may not be associated with susceptibility to psoriasis.     

The SNP rs1883832 in CD40 Gene and Risk of Atherosclerosis in Chinese Population: A Meta-Analysis

Background

The complications of atherosclerosis such as coronary and cerebrovascular disease, are the most prevalent causes of mortality and morbidity worldwide. A single nucleotide polymorphism (SNP) rs1883832 (-1C/T) in CD40 gene has been recently suggested to contribute to the susceptibility to atherosclerosis in Chinese population; however, previous genetic association studies yielded inconsistent results.

Methods

A meta-analysis of eligible studies reporting the association between rs1883832 and atherosclerosis in Chinese population was carried out.

Results

Pooling 7 eligible case-control studies involving 2129 patients and 1895 controls demonstrated a significant association between rs1883832 and atherosclerosis under dominant model [odds ratio (OR) = 1.631, 95% confidence interval [CI] [1.176, 2.260] in Chinese population with evident heterogeneity. Meta-regression analysis indicated that the heterogeneity could be completely explained by disease category. In subgroup analysis, rs1883832 conferred ORs of 2.866 (C/C versus T/T, 95%CI [2.203, 3.729]) and 1.680 (C/T versus T/T, 95%CI [1.352, 2.086]) for coronary artery disease (CAD) under co-dominant model without heterogeneity. Similar results were obtained for acute coronary syndrome (ACS) (C/C versus T/T, 3.674, 95%CI [2.638, 5.116]; C/T versus T/T, 1.981, 95%CI [1.483, 2.646]). The other genetic models including dominant, recessive and additive models, yielded consistent results without heterogeneity for CAD and ACS, respectively. However, a protective role was found for C allele in ischemic stroke (IS) under recessive model (0.582, 95%CI [0.393, 0.864]) and additive model (0.785, 95%CI [0.679, 0.909]) with reduced heterogeneity.

Conclusions

This meta-analysis provided evidence of association of rs1883832 C allele with an overall increased risk of atherosclerosis but distinct effect of C allele on CAD (including ACS) and IS in Chinese population, respectively.     

Analysis of the polymorphisms XRCC1Arg194Trp and XRCC1Arg399Gln in gliomas

XRCC genes (X-ray cross-complementing group) were discovered mainly for their roles in protecting mammalian cells against damage caused by ionizing radiation. Studies determined that these genes are important in the genetic stability of DNA. Although the loss of some of these genes does not necessarily confer high levels of sensitivity to radiation, they have been found to represent important components of various pathways of DNA repair. To ensure the integrity of the genome, a complex system of DNA repair was developed. Base excision repair is the first defense mechanism of cells against DNA damage and a major event in preventing mutagenesis. Repair genes may play an important role in maintaining genomic stability through different pathways that are mediated by base excision. In the present study, we examined XRCC1Arg194Trp and XRCC1Arg399Gln polymorphism using PCR-RFLP in 80 astrocytoma and glioblastoma samples. Patients who had the allele Trp of the XRCC1Arg194Trp polymorphism had an increased risk of tumor development (OR = 8.80; confidence interval at 95% (95%CI) = 4.37-17.70; P < 0.001), as did the allele Gln of XRCC1Arg399Gln (OR = 1.01; 95%CI = 0.53-1.93; P = 0.971). Comparison of overall survival of patients did not show significant differences. We suggest that XRCC1Arg194Trp and XRCC1Arg399Gln polymorphisms are involved in susceptibility for developing astrocytomas and glioblastomas.     

XRCC3 Thr241Met polymorphism and risk of acute myeloid leukemia in a Romanian population

Background

DNA repair systems have a critical role in maintaining the genome integrity and stability. DNA repair gene polymorphisms may influence the capacity to repair DNA damage, and thus lead to an increased cancer susceptibility. X-ray repair cross-complementing groups 3 (XRCC3), a DNA repair gene, may be involved in acute myeloid leukemia susceptibility. The objective of the current study was to investigate the association of Thr241Met polymorphism of XRCC3 gene with the risk of acute myeloid leukemia (AML).

Methods

This study included 78 AML patients and 121 healthy individuals without cancer. We used polymerase chain reaction-restriction fragment length polymorphism assay to determine XRCC3 genotypes.

Results

The XRCC3 variant genotype (Thr/Met+Met/Met) was more frequent in AML patients than in healthy controls (OR = 2.76, 95% CI: 1.52-4.98, P = 0.001). Our study revealed a statistically significant association between variant genotype (Thr/Met+Met/Met) and AML de novo compared to secondary AML (P = 0.007). No significant associations were found between any genotype and age at diagnosis, number of white blood cells and subtype of AML. Overall survival of patients with Thr/Thr genotype was better than those of variant Thr/Met and Met/Met genotypes.

Conclusions

Our findings indicate that the XRCC3 Thr241Met polymorphism may be a genetic risk factor for AML, particularly in male patients with de novo AML from the central part of Romania.