东北地区汉族人群DNA修复基因XPD单核苷酸多态性与胃癌的相关性

目的:研究核苷酸切除修复基因XPD单核苷酸多态性与东北地区汉族人群胃癌风险的关系.方法:以聚合酶链反应-限制性片段长度多态性方法分析了238例胃癌患者标本XPD基因Asp312Asn和Lys751Gln多态性,比较不同基因型与胃癌风险的关系.结果:Lys751Gln多态在胃癌患者中的分布和正常对照组差异不显著,与胃癌风险无关.胃癌患者中Asp/Asn和Asn/Asn基因型频率明显高于正常对照组(P=0.041);与携带312Asp/Asp基因型者比较,携带至少1个312Asn等位基因者(即Asp/Asn和Asn/Asn基因型)罹患胃癌的风险增加1.901倍(95%CI:1.119-3.229).结论:XPD基因Asp312Asn多态是东北地区汉族人群胃癌遗传易感因素.     

XPD Asp312Asn polymorphism is a risk factor for prostate cancer

Purpose

The association between Asp312Asn and Lys751Gln polymorphisms of Xeroderma pigmentosum Group D (XPD) and prostate cancer risk are still inconclusive. For better understanding of the effects of these two polymorphisms on prostate cancer risk, a meta-analysis was performed.

Methods

An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and prostate cancer risk was assessed by odds ratio (OR) with the corresponding 95?% confidence interval (95?% CI).

Results

A total of seven case–control studies were identified, among which five studies (1,257 cases and 1,956 controls) were eligible for Asp312Asn polymorphism and six studies (1,451 cases and 2,375 controls) were eligible for Lys751Gln polymorphism. Asp312Asn polymorphism was associated with an increased risk of prostate cancer in additive and recessive genetic models (additive model: OR?=?1.68, 95?% CI?=?1.28–2.22, P?=?0.00; recessive model: OR?=?1.65, 95?% CI?=?1.27–2.15, P?=?0.00). In the subgroup analysis, Asp312Asn polymorphism was associated with an increased risk of prostate cancer among Asians in all three genetic models (additive model: OR?=?2.09, 95?% CI?=?1.39–3.14, P?=?0.00; dominant model: OR?=?1.49, 95?% CI?=?1.12–1.98, P?=?0.01; recessive model: OR?=?1.93, 95?% CI?=?1.31–2.83, P?=?0.00). However, no significant associations were found between Lys751Gln polymorphism and prostate cancer risk in the overall analyses or the subgroup analyses by ethnicity.

Conclusions

The results of this meta-analysis indicate that the XPD Asp312Asn polymorphism is a risk factor for prostate cancer development.     

Association Between XPD Lys751Gln and Asp312Asn Polymorphisms and Hepatocellular Carcinoma Risk: A Systematic Review And Meta-Analysis

Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for DNA repair. Studies investigating the association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. The aim of this study was to quantitatively summarize the evidence for such an association.Eligible studies were identified by searching electronic databases including PubMed, Embase, Cochrane library, and CBM, Chinese Biomedical Literature Database, for the period up to October 2014. The association of XPD Lys751Gln and Asp312Asn polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).Finally, a total of 11 studies with 4322 cases and 4970 controls were included for XPD Lys751Gln polymorphism and 6 studies with 2223 cases and 2441 controls were available for XPD Asp312Asn polymorphism. With respect to XPD Lys751Gln polymorphism, statistically significant increased HCC risk was found when all studies were pooled into the meta-analysis (Gln/Gln vs Lys/Lys: OR = 1.363, 95% CI 1.065–1.744, P = 0.014; Lys/Gln vs Lys/Lys: OR = 1.205, 95% CI 1.099–1.321, P = 0.000; Gln/Gln+Lys/Gln vs Lys/Lys: OR = 1.300, 95% CI 1.141–1.480, P = 0.000). In subgroup analyses by ethnicity, source of control, Hardy–Weinberg equilibrium (HWE) in controls, hepatitis B virus (HBV) infection, and statistically significant increase of HCC risk was found in East Asians, population-based studies, studies consistent with HWE, and HBV-positive subjects, but not in mixed/other populations, hospital-based studies, studies deviating from HWE, and HBV-negative subjects. With respect to XPD Asp312Asn polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses.The results suggest that the XPD Lys751Gln polymorphism contributes to increased HCC susceptibility, especially in East Asian populations. Further, large and well-designed studies are required to validate this association.     

Excision repair cross-complementing group 2/Xeroderma pigmentousm complementation group D (ERCC2/XPD) genetic variations and susceptibility to diffuse large B cell lymphoma in Egypt

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous neoplasm. Although several genetic and environmental factors have been postulated, no obvious risk factors have been emerged for DLBCL in the general population. DNA repair systems are responsible for maintaining the integrity of the genome and protecting it against genetic alterations that can lead to malignant transformation. The current study aimed at investigating the possible role of ERCC2/XPD Arg156Arg, Asp312Asn and Lys751Gln genetic polymorphisms as risk factors for DLBCL in Egypt. The study included 81 DLBCL patients and 100 healthy controls. Genotyping of the studied genetic polymorphisms was performed by polymerase chain reaction–restriction fragment length polymorphism technique. Our results revealed that there was no statistical difference encountered in the distribution of ?Asp312Asn and ?Lys751Gln polymorphic genotypes between DLBCL cases and controls, thus it could not considered as molecular risk factors for DLBCL in Egyptians. However, Arg156Arg polymorphism at exon-6 conferred twofold increased risk of DLBCL (OR 2.034, 95 %CI 1.015–4.35, p = 0.43), and the risk increased when co-inherited with Lys751Gln at exon-23 (OR 3.304, 95 %CI 1.113–9.812, p = 0.038). In conclusion, ERCC2/XPD Arg156Arg polymorphism might be considered as a genetic risk factor for DLBCL in Egyptians, whether alone or conjoined with Lys751Gln.     

核苷酸切除修复基因ERCC1、XPD和XPC多态性与燃煤污染型地方性砷中毒的关系研究

目的 探讨核苷酸切除修复基因ERCCI、XPD、XPC不同基因型与燃煤污染型砷中毒发病风险的关系.方法 以贵州省兴仁县交乐村燃煤污染型砷中毒病区229例砷中毒患者作为病例组,以有相似生活习惯、无燃用高砷煤史的非砷暴露村大果朵村198名居民作为对照组,每人抽取外周静脉血约2 ml提取DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术进行ERCC1 C8092A 、XPD Lys751 Gln、XPD Asp312Asn、XPD Arg156Arg、XPC P(AT+/-)多态位点检测.结果 病例组ERCC1 C8092A位点CA/AA基因型分布频率[ CA:29.78％ (67/225)、AA:10.67％ (24/225)]显著高于对照组[CA:23.08％( 45/195)、AA:5.13％ (10/195),x2=8.116,P＜0.05];其余各基因多态位点的基因型分布频率差异无统计学意义(x2值分别为5.649、4.394、0.865、1.490,P均＞0.05).携带ERCCI 8092CA+ AA、XPD Lys751Gln+ Gln751Gln 、XPD Asp312Asn+ Asn312Asn基因型个体分别较携带ERCC1 8092CC、XPD Lys751Lys、XPD Asp312Asp基因型个体发生砷中毒的风险升高1.780、1.681、1.790倍(95％CI分别为1.174～2.698、1.081～2.615和1.014～3.158,P均＜0.05);单一的XPD 基因Arg156Arg位点、XPC基因P(AT+/-)位点对砷中毒的发病风险没有影响(P均＞0.05).结论 核苷酸切除修复基因ERCC1 C8092A、XPD Lys751 Gln和Asp312Asn位点的多态性与燃煤污染型砷中毒的发病风险有关.     

XPD基因单核苷酸多态性与晚期非小细胞肺癌对铂类药物敏感性的关系

目的 研究DNA修复基因着色性干皮病基因(XPD) Lys751Gln和XPD Asp312Asn基因多态性与非小细胞肺癌化疗铂类敏感性的关系.方法 收集经病理学确诊的晚期非小细胞肺癌87例,所有病例化疗前抽静脉血,提取DNA,用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测XPD Lys751Gln和XPD Asp312Asn基因型,比较不同基因型与铂类化疗疗效的关系及与无进展生存时间的关系.结果 总有效率43.7%,CR 3例(3.45%),PR 35例(40.23%),SD 20例(22.99%),PD 29例(33.33%),携带XPD751Lys/Lys、Lys/GIn基因型的患者,客观有效(CR+PR)分别为36例(48.6%)、2例(15.4%)二者相比差异有统计学意义(P=0.026).携带XPD 312Asp/Asp、Asp/Asn基因型的患者,客观有效(CR+PR)分别为35例(40.23%)、3例(30.0%)二者相比差异无统计学意义(P=0.556).携带XPD751 Lys/Lys、Lys/Gln与XPD312 Asp/Asp、Asp/Asn基因型的患者无进展生存时间(PFS)分别为6.7和5.9个月、6.5和6.4个月,无统计学意义(P=0.170、P=0.674).Cox回归模型分析显示XPD751位点基因型为Lys/Gln的患者疾病进展风险是基因型为Lys/Lys的患者的2.383倍(P=0.006).XPD751位点基因型为Lys/Gln可能是疾病进展较早的因素.结论 XPD Lys751Gln单核苷酸多态性与晚期非小细胞肺癌铂类药物耐药有关.未发现XPD基因单核苷酸多态性与无进展生存时间相关,但XPD751位点基因型为Lys/Gln可能是疾病进展较早的危险因素.     

XPC Lys939Gln polymorphism,smoking and risk of sporadic colorectal cancer among Malaysians

AIM: To investigate the risk association of xeroderma pigmentosum group C (XPC ) Lys939Gln polymorphism alone and in combination with cigarette smoking on colorectal cancer (CRC) predisposition. METHODS: Peripheral blood samples of 510 study subjects (255 CRC patients, 255 controls)were collected. DNA was extracted and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. The association between polymorphic genotype and CRC predisposition was determined using the OR and 95%CI. RESULTS: The frequency of the homozygous variant (Gln/Gln) genotype was significantly higher in cases compared with controls (16.0% vs 10.2%, P = 0.049). The Gln/Gln genotype of XPC showed a significantly higher association with the risk of CRC (OR = 1.884; 95%CI: 1.082-3.277; P = 0.025). In the case of allele frequencies, variant allele C was associated with a significantly increased risk of CRC (OR = 1.375; 95%CI: 1.050-1.802; P = 0.020). Moreover, the risk was markedly higher for those who were carriers of the Gln/Gln variant genotype and were also cigarette smokers (OR = 3.409; 95%CI: 1.061-10.949; P = 0.032). CONCLUSION: The XPC Gln/Gln genotype alone and in combination with smoking increases the risk of CRC among Malaysians.     

Lack of association between XPD Lys751Gln and Asp312Asn polymorphisms and colorectal cancer risk: a meta-analysis of case�Ccontrol studies

Purpose  

The published data on the association between xeroderma pigmentosum group D (XPD) Lys751Gln and Asp312Asn polymorphisms and colorectal cancer remained controversial. The present meta-analysis of literatures was performed to derive a more precise estimation of the relationship.     

Association between esophageal cancer risk and EPHX1 polymorphisms:A meta-analysis

AIM:To summarize the relationship between p.Tyr113His and p.His139Arg polymorphisms in microsomal epoxide hydrolase(EPHX1)and risk for esophageal cancer(EC).METHODS:The MEDLINE/PubMed and EMBASE databases were searched for studies of the association between EPHX1 polymorphisms and EC risk that were published from the database inception date to April2013.A total of seven case-control studies,including seven on p.Tyr113His(cases,n=1118;controls,n=1823)and six on p.His139Arg(cases,n=861;controls,n=1571),were included in the meta-analysis.After data extraction by two investigators working independently,the meta-analyses were carried out with STATA 11.0 software.Pooled odds ratios and 95%CI were calculated using a fixed-effects model or a random-effects model,as appropriate.RESULTS:The pooled EPHX1 p.Tyr113His polymorphism data showed no significant association with EC in any of the genetic models(OR=1.00,95%CI:0.70-1.48 for Tyr/His vs Tyr/Tyr;OR=1.10,95%CI:0.77-1.57 for His/His vs Tyr/Tyr;OR=1.06,95%CI:0.75-1.49 for a dominant model;OR=1.09,95%CI:0.89-1.34 for a recessive model).Similar results were obtained from the p.His139Arg polymorphism analysis(Arg/His vs His/His:OR=1.02,95%CI:0.84-1.23;Arg/Arg vs His/His:OR=0.96,95%CI:0.60-1.54;OR=1.03,95%CI:0.78-1.37 for the dominant model;OR=0.97,95%CI:0.61-1.56 for the recessive model).Subgroup analyses for ethnicity,subtype of EC,and source of controls(population-based or hospital-based)showed trends that were consistent with the pooled analysis(reported above),with no significant associations found.CONCLUSION:This meta-analysis suggests that the p.Tyr113His and p.His139Arg polymorphisms in EPHX1may not be associated with EC development.     

Xeroderma pigmentosum group D 751 polymorphism as a predictive factor in resected gastric cancer treated with chemo-radiotherapy

INTRODUCTION The xeroderma pigmentosum group D (XPD) gene en- codes a protein required for nucleotide excision repair (NER). This product recognizes and repairs a wide range of structurally unrelated lesions such as bulky adducts caused by UV light, envir…     

Prognostic importance of DNA repair gene polymorphisms of <Emphasis Type="Italic">XRCC1</Emphasis> Arg399Gln and <Emphasis Type="Italic">XPD</Emphasis> Lys751Gln in lung cancer patients from India

Purpose Inter individual variation in lung cancer susceptibility may be modulated in part through genetic polymorphisms in the DNA repair genes, especially the genes involved in the Base Excision Repair (BER) and nucleotide excision repair (NER) pathway. Two of the genetic polymorphisms, XRCC1Arg399Gln and XPD Lys751Gln have been extensively studied in the association with lung cancer risk, although published studies have been inconclusive. Methods In order to verify the role of the common variant alleles in the XPD gene, we have genotyped 211 lung cancer patients and 211 healthy controls using PCR-RFLP assays in a hospital based, case-control study in an Indian population. Logistic regression models were fit to examine the relationship between the log odds of lung cancer and each covariate. Overall Survival in relation to various genotypes and clinicopathological factors were analyzed using Kaplan Meier estimates and hazard ratios were calculated using Cox Regression analysis. Results The carriers of XRCC1 399 AA genotypes were at higher risk of lung cancer (OR = 2.1, 95% CI:1.224–3.669, P = 0.007) than carriers of GG genotype. Subjects carrying 751 AC genotype were at an increased risk of carcinoma of the lung (OR = 1.8; 95% CI:1.233–2.807, P = 0.003) than subjects with AA genotypes. Compared to the XRCC1 399 GG/ XPD 751 AA reference genotype, the combined variants, XRCC1 399 GG/ XPD 751 AC+CC (OR = 1.9, 95% CI: 1.037–3.481), P = 0.03), XRCC1 399 GA+AA/ XPD 751 AA (OR = 1.7, 95% CI: 1.020–2.833, P = 0.04), XRCC1 399 GA+AA/XPD 751 AC+CC (OR = 2.7, 95% CI: 1.582–4.864, P = 0.01), had significantly higher odds ratios. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival, the risk being significant for the XRCC1 gene polymorphism (P = 0.01 by log-rank test). The hazard of dying was significant for the XRCC1 399 AA genotype (HR = 3.04, 95%CI: 1.393–6.670, P = 0.005). Higher tumour stage also came out as significant predictors of patient death. Conclusions These findings suggest that genetic polymorphisms in the DNA repair genes may modulate overall lung cancer susceptibility and that pathological stage and XRCC1 Arg399Gln independently predicted overall survival among Indian lung cancer patients.     

XPD gene polymorphisms and the effects of induction chemotherapy in cytogenetically normal de novo acute myeloid leukemia patients

Background

Cytogenetically normal acute myeloid leukemia (AML) represents nearly half of newly diagnosed de novo AML cases. XPD is one of the DNA repair proteins, whose genetic polymorphisms are thought to affect their function as regards response to chemotherapeutic drugs and chemotherapy-induced toxicities.

Subjects and methods

We investigated the XPD Asp312Asn and Lys751Gln polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in 51 newly diagnosed cytogenetically normal de novo AML patients. The response to the standard induction chemotherapy protocol and chemotherapy-induced toxicities were monitored.

Results

The XPD Asp312Asn GG genotype was the most frequent (57%) followed by the GA variant (37%), and the AA variant was the least frequent (6%). As regards the XPD Lys751Gln polymorphism, the AA genotype was the most frequent (49%), followed by the AC (39%) and CC (12%) variants. These variants were not associated with age, sex, FAB subtype, CNS infiltration, chemotherapy-induced hepatotoxicity, nephrotoxicity, or metabolic toxicity. The XPD Lys751Gln CC polymorphic variant was associated with chemotherapy-induced cardiotoxicity and lower chance to achieve response to induction chemotherapy.

Conclusion

XPD Lys751Gln and not Asp312Asn polymorphism was associated with chemotherapy-induced cardiotoxicity and response to induction chemotherapy in newly diagnosed cytogenetically normal AML patients. Pretreatment assay of XPD Lys751Gln may help to anticipate cardiotoxicity in those at risk. Moreover, it may be considered a prognostic marker in AML cases. However, further large scale research is needed to verify its usefulness.     

DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency

Coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. In this study, we investigated the effects of the XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on the presence and the severity of CAD. We also investigated the presence of DNA damage in the peripheral lymphocytes of patients with CAD by using the micronucleus (MN) test and the effect of XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on this damage. The study population consisted of 147 patients with angiographically documented CAD and 48 healthy controls. No association between XPD Lys751Gln or XRCC1 Arg399Gln polymorphisms and the presence or the severity of CAD was observed. On the other hand, a significantly higher frequency of MN was observed in CAD patients compared with controls (5.7 ± 1.9 vs 5.0 ± 2.1, respectively, P = 0.018). We found an elevated frequency of MN in CAD patients with the XPD 751Gln allele (Gln/Gln genotype) or the XRCC1 399Gln (Arg/Gln or Gln/Gln genotypes) allele compared with the XPD 751Lys (Lys/Lys genotype) allele or XRCC1 399 Arg (Arg /Arg genotype) allele, respectively. These preliminary results suggest that XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms may not be a significant risk factor for developing CAD. In addition, our results indicate that the MN frequency is associated with presence, but not severity, of CAD and is related to the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms, suggesting an elevated frequency of MN in CAD patients with the XPD 751Gln or XRCC1 399Gln alleles.     

APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans

AIM: To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.METHODS: Two hundred forty-seven colorectal cancer (CRC) patients and three hundred cancer-free controls were enrolled in this study. Four polymorphisms (OGG1 Ser326Cys, APE1 Asp148Glu, -141T/G in the promoter region, and XRCC1 Arg399Gln) in components of the base excision repair pathway were determined in patient blood samples using polymerase chain reaction with confronting two-pair primers. The baseline information included age, gender, family history of cancer, and three behavioral factors [smoking status, alcohol consumption, and body mass index (BMI)]. χ² tests were used to assess the Hardy-Weinberg equilibrium, the distributions of baseline characteristics, and the four gene polymorphisms between the cases and controls. Multivariate logistic regression analyses were conducted to analyze the correlations between the four polymorphisms and CRC risk, adjusted by the baseline characteristics. Likelihood ratio tests were performed to analyze the gene-behavior interactions of smoking status, alcohol consumption, and BMI on polymorphisms and CRC susceptibility.RESULTS: The APE1 148 Glu/Glu genotype was significantly associated with an increased risk of colorectal cancer (OR = 2.411, 95%CI: 1.497-3.886, P < 0.001 relative to Asp/Asp genotype). There were no associations between OGG1, XRCC1, or APE1 promoter polymorphisms and CRC risk. A multivariate analysis including three behavioral factors showed that the APE1 148 Glu/Glu genotype was associated with an increased risk for CRC among both smokers and non-smokers, non-drinkers and individuals with a BMI ≥ 25 kg/m² (ORs = 2.356, 3.299, 2.654, and 2.581, respectively). The XRCC1 399 Arg/Gln genotype was associated with a decreased risk of CRC among smokers and drinkers (OR = 0.289, 95%CI: 0.152-0.548, P < 0.001, and OR = 0.327, 95%CI: 0.158-0.673, P < 0.05, respectively). The APE1 promoter polymorphism -141 T/G genotype was associated with a reduced risk of colorectal cancer among subjects with a BMI < 25 kg/m² (OR = 0.214, 95%CI: 0.069-0.660, P < 0.05 relative to T/T genotype). There were significant gene-behavior interactions between smoking status and XRCC1 Arg399Gln, as well as BMI and APE1 -141T/G polymorphism (all P < 0.05).CONCLUSION: APE1 Asp148Glu is associated with increased CRC risk and smoking alters the association between XRCC1 Arg399Gln and CRC risk in the Chinese Han population.     

MiR-146a rs2910164 polymorphism increases risk of gastric cancer: A meta-analysis

AIM: To systematically evaluate the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer.METHODS: A comprehensive electronic search was conducted for articles published up until January 27, 2014 in Medline (PubMed), Excerpta Medica Database (Embase), the Cochrane Library and Google Scholar. Only case-control studies published in English that evaluated the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer were included. Furthermore, only studies with sufficient data allowing for calculation of odds ratio (OR) and corresponding 95% confidence interval (CI) were included. These values were used in the quantitative synthesis to assess the strength of the association between the miR-146a rs2910164 polymorphism and risk of gastric cancer.RESULTS: The database search identified 1002 eligible studies, of which seven (comprising 4112 cases and 5811 controls) were included for the meta-analysis. The results indicate that miR-146a rs2910164 polymorphism is more likely to be associated with gastric cancer risk. In the overall analysis, a significantly increased cancer risk was found in the heterozygote (GG vs GC) comparison (OR = 1.14, 95%CI: 1.03-1.27; P = 0.01 for pooled OR). In the ethnicity subgroup analysis, a similar result was found among Caucasians (OR = 1.36, 95%CI: 1.01-1.85; P = 0.04 for pooled OR). In the stratified analysis by quality of studies, a significantly increased cancer risk was found in the heterozygote comparison among high quality studies (OR = 1.12, 95%CI: 1.01-1.26; P = 0.04 for pooled OR). When stratified on the basis of sample size, a significantly increased cancer risk was found among small sample size subgroups for the allelic (G vs C: OR = 1.16, 95%CI: 1.03-1.30; P = 0.01), homozygote (GG vs CC: OR = 1.33, 95%CI: 1.03-1.73; P = 0.03) and recessive model (GG vs GC + CC: OR = 0.05, 95%CI: 0.00-0.10; P = 0.03) comparisons.CONCLUSION: The miR-146a rs2910164 polymorphism is associated with increased gastric cancer risk, particularly evident in high quality studies with small sample sized Caucasian populations.     

Polymorphisms in DNA repair genes and therapeutic outcomes of AML patients from SWOG clinical trials

Repair of damage to DNA resulting from chemotherapy may influence drug toxicity and survival in response to treatment. We evaluated the role of polymorphisms in DNA repair genes APE1, XRCC1, ERCC1, XPD, and XRCC3 in predicting therapeutic outcomes of older adults with acute myeloid leukemia (AML) from 2 Southwest Oncology Group (SWOG) clinical trials. All patients received standard chemotherapy induction regimens. Using logistic and proportional hazards regression models, relationships between genotypes, haplotypes, and toxicities, response to induction therapy, and overall survival were evaluated. Patients with XPD Gln751C/Asp312G ('D') haplotype were more likely to have complete response (OR = 3.06; 95% CI, 1.44-6.70) and less likely to have resistant disease (OR = 0.32; 95%CI, 0.14-0.72) than patients with other haplotypes. ERCC1 polymorphisms were significantly associated with lung (P = .037) and metabolic (P = .041) toxicities, and patients with the XRCC3 241Met variant had reduced risk of liver toxicity (OR = 0.32; 95%CI, 0.11-0.95). Significant associations with other toxicities were also found for variant XPD genotypes/haplotypes. These data from clinical trials of older patients treated for AML indicate that variants in DNA repair pathways may have an impact on both outcomes of patients and toxicities associated with treatments. With validation of results in larger samples, these findings could lead to optimizing individual chemotherapy options.     

XRCC1和XPD单核苷酸多态性与非小细胞肺癌铂类药物化疗敏感性的关系

目的研究X线修复交叉互补基因1（XRCC1）和着色性干皮病基因（XPD）单核苷酸多态性与老年晚期非小细胞肺癌（NSCLC）铂类药物化疗敏感性关系。方法应用聚合酶链反应结舍限制性片段长度多态性（PCR-RFLP）的方法检测81例以铂类药物为主要化疗方案的NSCLC患者XRCC1 Arg399Gln和XPD Lys751Gin基因型多态性，采用非条件Logistic回归分析不同基因型与化疗疗效的关系。结果81例患者化疗总有效率为35．8％，其中完全缓解（CR）、部分缓解（PR）、稳定（SD）和进展（PD）患者分别为0、29、31、21例。携带至少1个XRCC1 399Arg等位基因的患者化疗敏感性是携带Gln／Gln基因型患者的4.52倍（OR=4．52，95％CI=1.11—18．38）。未发现XPD Lys751Gin遗传多态与化疗敏感性相关。结论XRCC1 Arg399Gln多态可能与晚期NSCLC铂类药物化疗敏感性有关。     

Toll-like receptor 4 and NOD2／CARD15 mutations in Hungarian patients with Crohn＇s disease： Phenotype-genotype correlations

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.     

Clinical outcome of small hepatocellular carcinoma after different treatments:A meta-analysis

AIM:To compare clinical outcomes between surgical resection(RES)and nonsurgical-RES(nRES)ablation therapies for small hepatocellular carcinoma(HCC).METHODS:MEDLINE,Embase and Cochrane Library databases were systematically searched for studies of RES and nRES treatments for small HCC between January 2003 and October 2013.The clinical outcome measures evaluated included overall survival rate,disease-free survival rate,adverse events,and local recurrence rate.Odds ratios(ORs)with 95%CIs were calculated using either the fixed effects model or random effects model.Theχ2 and I2 tests were calculated to assess the heterogeneity of the data.Funnel plots were used to assess the risk of publication bias.RESULTS:Our analysis included 12 studies that consisted of a total of 1952 patients(RES vs nRES),five studies that consisted of 701 patients[radiofrequency ablation(RFA)vs percutaneous ethanol injection(PEI)],and five additional studies[RFA vs RFA+transcatheter arterial chemoembolization(TACE)]that all addressed the treatment of small HCC.For cases of RES vs nRES,there was no significant difference in the 1-year(OR=0.99,95%CI:0.87-1.12,P=0.85)or 3-year(OR=0.97,95%CI:0.84-1.11,P=0.98)overall survival rate;however,there was a significant increase in the RES group in the 5-year overall survival rate(OR=0.81,95%CI:0.68-0.95,P=0.01).The 1-year(OR=0.94,95%CI:0.82-1.08,P=0.37)and 5-year(OR=0.99,95%CI:0.85-1.14,P=0.85)disease-free survival rates showed no significant differences between the two groups.The3-year disease-free survival rate(OR=0.81,95%CI:0.69-0.96;P=0.02)was higher in the RES group.For cases of RFA vs PEI,our data analysis indicated that RFA treatment was associated with significantly higher2-year(OR=0.76,95%CI:0.58-0.99,P=0.043)and3-year(OR=0.73,95%CI:0.54-0.98,P=0.039)overall survival rates;however,there were no significant differences in the 1-year(OR=0.92,95%CI:0.72-1.17,P=0.0502)overall survival rate or incidence of adverse events(OR=1.84,95%CI:0.76-4.45,P=0.173).For cases of RFA vs RFA+TACE,there were no significant differences in the 1-year(OR=1.17,95%CI:0.88-1.56,P=0.27)or 3-year(OR=1.25,95%CI:0.90-1.73,P=0.183)overall survival rate;however,the 5-year overall survival rate(OR=3.19,95%CI:1.51-6.74,P=0.002)in patients treated by RFA+TACE was higher than that treated by RFA alone.CONCLUSION:Surgical resection is superior to nonsurgical ablation for the treatment of small HCC.Among the studies analyzed,RFA is the most efficacious single nonsurgical ablation treatment.     

TNF-a-308 polymorphism and risk of digestive system cancers:A meta-analysis

AIM:To evaluate the association between the tumour necrosis factor alpha-308(TNF-a-308)gene polymorphism and the risk of digestive system cancers.METHODS:All eligible case-control studies published up to December 2012 were identified by searching PubMed,Web of Science,Embase and China National Knowledge Internet without language restrictions.The risk of digestive system cancers associated with the TNF-a-308 polymorphism was estimated for each study using odds ratio(OR)together with its 95%CI,respectively.Cochrane Collaboration RevMan 5.1 was used to perform the analysis.Aχ2-test-based Q statistic test and an I2test were performed to assess the betweenstudy heterogeneity.When the Q test was significant(P<0.05)or I2>50%,the random effects model was used,otherwise the fixed effects model was used.RESULTS:Fifty-eight studies from fifty-five publications with a total of 9986 cancer patients and 15511 healthy controls were included.Overall,a significant association was found between the TNF-a-308 polymorphism and the risk of digestive system cancers[dominant model:OR=1.23,95%CI:1.09-1.39,(G/A)vs(G/G):OR=1.15,95%CI:1.02-1.28,(A/A)vs(G/G):OR=1.44,95%CI:1.19-1.73,recessive model:OR=1.38,95%CI:1.15-1.66].Furthermore,when the analysis was stratified by ethnicity,similar results were observed in both the Asian and Caucasian populations,except for the dominant model and heterozygote comparisons in the Asian population[dominant model:OR=1.24,95%CI:0.99-1.56,(G/A)vs(G/G):OR=1.09,95%CI:0.96-1.24].When the cancer type subgroups were examined,similar results were detected in gastric and hepatocellular carcinomas;however,no significant association was observed among other digestive system cancers.CONCLUSION:The TNF-a-308 gene polymorphism may be significantly associated with the risk of gastric and hepatocellular carcinomas,but not colorectal,pancreatic,or oesophageal cancer,in the Asian population.