The XPD Lys751Gln Polymorphism has Predictive Value in Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Systemic Review and Meta-analysis

Background: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphismregarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapyhas been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performeda meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation andoptimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligiblestudies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) wereused to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-freesurvival (PFS) and overall survival (OS). Results: A total of 17 studies including 2,286 patients met the inclusioncriteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response tooxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups. However, poor PFSand OS of CRC patients treated with oxaliplatin-based regimens were significantly related to the XPD 751Glnallele in the dominant model (PFS: HR=2.10, 95%CI: 1.65-2.67; OS: HR=3.18, 95%CI: 1.57-6.47). On stratifiedanalysis by ethnicity, these relationships were more pronounced in Asians (PFS: HR=2.49, 95%CI: 1.79-3.47;OS: HR=5.25, 95%CI: 3.46-7.94) than in Caucasians (PFS: HR=1.73, 95%CI: 1.22-2.46; OS: HR=1.78, 95%CI:1.06-2.99). Conclusions: The XPD Lys751Gln polymorphism may have prognostic value in patients with CRCundergoing oxaliplatin-based chemotherapy.     

Genetic Association between ERCC5 rs17655 Polymorphism and Colorectal Cancer Risk: Evidence Based on a Meta-analysis

Background: Previous studies evaluating the association between the excision repair cross complementinggroup 5 (ERCC5) gene rs17655 polymorphism and colorectal cancer susceptibility generated controversial results.To generate large-scale evidence on whether the ERCC5 rs17655 polymorphism might indeed be associatedwith colorectal cancer susceptibility, the present meta-analysis was performed. Materials and Methods: Datawere collected from PubMed, Embase and Web of Science, with the last report up to Apr 03, 2015. Odds ratios(ORs) with 95% confidence intervals (CIs) were used to assess the strength of any association. Results: A total ofnine studies including 5,102 cases and 6,326 controls based on the search criteria were included and significantassociations were found between ERCC5 rs17655 polymorphism CG vs GG overall (OR = 1.29, 95% CI=1.18~1.40) and in the dominant model (OR=1.23, 95% CI =1.13~1.33). On subgroup analysis by ethnicity andsource of controls, the ERCC5 rs17655 polymorphism was found to correlate with the pathogenesis of colorectalcancer among Asians and Caucasians and with hospital-based populations. Conclusions: This meta-analysissuggests that the ERCC5 rs17655 polymorphism might contribute to genetic susceptibility to colorectal cancer.     

Effect of the ERCC1 (C118T) Polymorphism on Treatment Response in Advanced Non-Small Cell Lung Cancer Patients Undergoing Platinum-Based Chemotherapy

For advanced non-small-cell lung cancer (NSCLC) cases, a platinum-based regimen is the first-line chemotherapy treatment. The excision repair cross-complementing group 1 (ERCC1) plays an important role in DNA repair and has been related to resistance to platinum chemotherapy. This study aimed to investigate the effects of the ERCC1 (C118T) polymorphism on treatment response in 26 Thai advanced NSCLC patients receiving first line platinum-based chemotherapy during January to July 2015 at King Chulalongkorn Memorial Hospital (KCMH). DNA was extracted from peripheral blood lymphocytes and the single nucleotide polymorphism of ERCC1 was genotyped using a real-time PCR method with the TaqMan assay. The distribution of C/C, C/T and T/T genotypes was 57.7 %, 34.6 % and 7.7 %, respectively. The response rate to platinum-based chemotherapy in the wild type (C/C) of ERCC1 (C118T) was better than with the variant types (C/T and T/T) but the difference was not statistically significant (29.7% vs 9.1%, P=0.274). The results showed that a genetic polymorphism in ERCC1 might influence patient response to platinum-based chemotherapy. Further multicenter studies are now required to confirm the results of our study.     

ERCC1基因多态性与晚期非小细胞肺癌患者铂类化疗疗效的关系

背景与目的有关ERCC1基因多态性是否影响接受含铂化疗的晚期非小细胞肺癌患者疗效及生存的研究结果不相一致。本研究前瞻性研究90例接受含铂方案化疗的初治晚期非小细胞肺癌患者ERCC1基因C8092A和第118位密码子多态性与疗效的关系。方法全部患者均接受含铂联合方案化疗,采用测序法对患者基因型进行分型,比较不同基因型与疗效的关系。结果ERCC1C8092A基因型频率分别为CC40.0%(36/90)、CA48.9%(44/90)、AA11.1%(10/90),第118密码子基因型频率分别为CC58.9%(53/90)、CT34.4%(31/90)、TT6.7%(6/90)。C8092ACC基因型有效率与CA、AA基因型无统计学差异(33.3%vs29.6%,P=0.71),ERCC1118CC基因型患者有效率与CT和TT基因型无统计学差异(32.1%vs24.3%,P=0.43)。C8092ACC基因型患者与CA和AA基因型PFS无统计学差异(5.2个月vs5.4个月,P=0.62),ERCC1118CC基因型患者CT和TT基因型PFS无统计学差异(5.5个月vs5.3个月,P=0.59)。结论ERCC1C80...     

GSTP1, ERCC1 and ERCC2 Polymorphisms,Expression and Clinical Outcome of Oxaliplatin-based Adjuvant Chemotherapy in Colorectal Cancer in Chinese Population

Aim: Platinum agents have shown to be effective in the treatment of colorectal cancer. We assessed whethersingle nucleotide polymorphisms (SNPs) in GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln might predictthe overall survival in patients receiving oxaliplatin-based chemotherapy in a Chinese population. Methods:SNPs of GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln in 335 colorectal cancer patients were assessedusing TaqMan nuclease assays. Results: At the time of final analysis on Nov. 2011, the median follow-up periodwas 37.7 months (range from 1 to 60 months). A total of 229 patients died during follow-up. Our study showedGSTP1 Val/Val (HR=0.44, 95% CI=0.18-0.98), ERCC1 C/C (HR=0.20, 95% CI=0.10-0.79) and ERCC2 G/G(HR=0.48, 95% CI=0.19-0.97) to be significantly associated with better survival of colorectal cancer. GSTP1Val/Val, ERCC1 C/C and ERCC2 G/G were also related to longer survival among patients with colon cancer,with HRs (95% CIs) of 0.41 (0.16-0.91), 0.16 (0.09-0.74) and 0.34 (0.16-0.91), respectively. Conclusion: GSTP1,GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln genotyping might facilitate tailored oxaliplatin-basedchemotherapy for colorectal cancer patients.     

Meta-analysis of Excision Repair Cross-complementation Group 1 (ERCC1) Association with Response to Platinumbased Chemotherapy in Ovarian Cancer

Recent studies suggested that the ovarian cancers with negative excision repair cross-complementation group1 enzyme (ERCC1) expression have a better response to platinum-based chemotherapy than those with positiveERCC1 expression. The objective of this study was to evaluate whether ERCC1 expression is associated withresponse to platinum-based chemotherapy in ovarian cancers. MEDLINE, PubMed, Web of Science and CNKIdatabases were used for searching studies relating to ERCC1 protein expression and response to platinum-basedchemotherapy in ovarian cancers. Statistical analysis was based on the method for a fixed effects meta-analysis.Pooled odds ratios (ORs) with 95% confidence intervals for ERCC1 protein expression and response to platinumbasedchemotherapy were generated. Publication bias was investigated with Begg’s test. Five studies involving306 patients with ovarian cancer were included. Compared to patients with positive ERCC1 expression, thosewith negative ERCC1 expression had a better response to platinum-based chemotherapy. The pooled OR was5.264 (95% CI: 2.928 – 9.464, P < 0.001) and publication bias was not found (P = 0.904). The result was similarin both in Asians and Caucasians (P < 0.001 and P = 0.028, respectively). ERCC1 protein e     

Associations of ERCC4 rs1800067 Polymorphism with Cancer Risk: an Updated Meta-analysis

Background: Results from previous studies concerning the association of ERCC4 rs1800067 polymorphismwith risk of cancer were inconsistent. To explore the exact relation with susceptibility, we conducted the presentmeta-analysis. Materials and Methods: Literature of electronic databases including PubMed, Web of Science,EMBASE, Wanfang and Chinese National Knowledge Infrastructure (CNKI) were systematically searched. ORsand their 95%CIs were used to assess the strength of associations between ERCC4 polymorphism and cancerrisk. Results: There was no significant association between ERCC4 rs1800067 AA or AG genotypes and overallrisk of cancer (AA vs. GG: OR=0.998, 95%CI=0.670-1.486, P=0.992; AG vs. GG: OR=0.970, 95%CI=0.888-1.061, P=0.508). A dominant genetic model also did not demonstrate significant association of (AA+AG)genotype carriers with altered risk of overall cancer (OR=0.985, 95%CI=0.909-1.068, P=0.719). In addition,no significant association was observed between A allele of ERCC4 rs1800067 A/G polymorphism and alteredcancer risk compared with G allele (OR=0.952, 95%CI=0.851-1.063, P=0.381). Subgroup analysis suggestedthat AA genotype carriers were significantly associated with decreased risk of glioma compared with wild-typeGG genotype individuals (OR=0.523, 95%CI=0.275-0.993, P=0.048). For subgroup of lung cancer, A allele ofERCC4 rs1800067 A/G polymorphism was significantly associated with decreased risk of lung cancer comparedwith G allele (OR=0.806, 95%CI=0.697-0.931, P=0.003). Conclusions: This meta-analysis indicated that ERCC4rs1800067 A/G polymorphism might not be associated with risk of overall cancer. However, individuals with theAA genotype were associated with significantly reduced risk of glioma compared with wild-type GG genotype;The A allele was associated with significantly reduced risk of lung cancer compared with G allele. Future largescalestudies performed in multiple populations are warranted to confirm our results.     

结肠癌组织中ERCC1表达及其临床意义

目的探讨结肠癌组织中ERCC1表达及其临床意义。方法应用采用免疫组化（即用型二步法）检测其ERCC1表达水平,术后均以奥沙利铂为主的方案化疗,所有入组患者随访3年以上。结果结肠癌组织中ERCC1表达阳性率为51%。ERCC1表达与患者性别、年龄、病理类型无明显相关性;与肿瘤局部浸润有关,但与淋巴结转移及TNM分期无明显相关性;ERCC1阴性患者,术后经奥沙利铂为主的方案化疗后2、3、4和5年生存率均高于阳性患者,经Logrank检验,两者有显著性差异;Cox回归分析显示ERCC1表达为结肠癌患者独立预后因素。结论ERCC1蛋白表达阴性患者应用以奥沙利铂为主的方案化疗可能获得生存受益;ERCC1表达水平可作为结肠癌患者术后辅助化疗方案的选择及预后判断的指标之一。     

ERCC1和XRCC1基因多态性与接受奥沙利铂化疗晚期大肠癌患者生存期的关系

目的: 探讨DNA损伤修复基因ERCC1 Asn118Asn和XRCC1 Arg399Gln多态性与接受奥沙利铂一线化疗的中国晚期大肠癌患者生存期的关系。 方法: 99例晚期大肠癌患者化疗前抽取静脉血并提取DNA,以real-time PCR法对ERCC1、XRCC1基因进行SNP分型。患者接受奥沙利铂为主的化疗方案化疗,比较不同基因型与患者生存期的关系。 结果: ERCC1 Asn118Asn基因位点在所研究的中国大肠癌患者中的突变频率为:C/C50.51%、C/T41.41%、T/T8.08%;XRCC1 Arg399Gln基因突变频率为:G/G52.53%、G/A38.38%、A/A9.09%。99例晚期大肠癌患者中位TTP为7个月。ERCC1C/C基因型患者中位TTP10个月,C/T+T/T型患者中位TTP5个月,二者有显著统计学差异(P<0.01);XRCC1G/G基因型中位TTP10个月,G/A+A/A基因型中位TTP5个月,二者比较差异有显著性(P<0.01)。两个基因联合多态性分析发现,同时携带ERCC1C/C和XRCC1G/G基因型、ERCC1C/C和XRCC1G/A+A/A基因型、ERCC1C/T+T/T和XRCC1G/G基因型、以及ERCC1C/T+T/T和XRCC1G/A+A/A基因型的患者中位TTP分别为11个月、6个月、5个月和5个月,4组比较差异有显著性(P<0.01)。 结论: ERCC1 Asn118Asn、XRCC1 Arg399Gln基因多态性与中国晚期大肠癌患者接受奥沙利铂一线化疗后的生存期有关。     

Prognostic Significance of Beclin-1 Expression in Colorectal Cancer: a Meta-analysis

Objective: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers.However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed toevaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients.Materials and Methods: All related studies were systematically searched in Pubmed, Embase, Springer andChinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed todetermine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were includedin our analysis. Results: Our data showed that high Beclin-1 expression in patients with CRC was associatedwith poor prognosis in terms of tumor distant metastasis (OR=2.090, 95%CI=1.061-4.119, p=0.033) and overallsurvival (RR=1.422, 95%CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1over-expression and tumor differentiation (OR=1.711, 95%CI=0.920-3.183, p=0.090). In addition, there was noevidence of publication bias as suggested by Egger’s tests for tumor distant metastasis (p=1.000), differentiation(p=1.000) and OS (p=0.308). Conclusions: Our present meta-analysis indicated that elevated Beclin-1 expressioniss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as anefficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.     

ERCC1蛋白在老年晚期非小细胞肺癌组织中的表达及临床意义

目的：探讨切除修复交叉互补基因1（ERCC1）在老年晚期非小细胞肺癌（NSCLC）组织中的表达情况及其临床意义。方法采用免疫组化法检测76例老年晚期NSCLC患者肿瘤组织中ERCC1的表达水平。结果76例老年晚期非小细胞肺癌组织中ERCC1蛋白表达阳性率为36．84％,与患者性别、病理类型、分化程度、临床分期及吸烟指数无关;ERCC1表达阳性组化疗有效率（17．86％）低于阴性组（43．75％）,差异有统计学意义（P＜0．05）;ERCC1表达阳性组中位生存期（MST）（10个月）短于阴性组（14个月）,但差异无统计学意义（P＞0．05）。结论 ERCC1蛋白表达水平是铂类药物化疗疗效的一个预测指标,有助于非小细胞肺癌个体化化疗方案的制定。     

大肠癌ERCC1的表达及其临床意义

目的探讨ERCC1在大肠癌中的表达及其临床意义。方法应用免疫组化方法检测了手术切除的59例大肠癌组织中ERCC1表达。采用卡方检验、Kaplan-Meiner生存曲线、Log-rank检验,分析其与临床病理特征的关系及对生存期的影响。结果 59例结直肠癌中,ERCC1阳性率为28.8%（17/59）。ERCC1表达情况与组织病理分化程度、性别、浸润深度、部位、有无淋巴结转移及临床分期无关（P〉0.05）。ERCC1在≤60岁的25例中阳性率为44.0%（11/25）,〉60岁的34例中阳性率为17.6%（6/34）,两者比较有统计学意义（P〈0.05）。ERCC1阴性病例4年生存率54.8%,ERCC1阳性病例4年生存率23.5%,两者差异无统计学意义（P〉0.05）。结论 ERCC1与肿瘤分化程度、临床分期、有无淋巴结转移及浸润深度等无关,提示ERCC1与肿瘤的不良生物学行为无关。对于以铂类为化疗基础的大肠癌,ERCC1阳性表达者,预后可能要差一些。     

胞苷脱氨酶基因遗传变异对结直肠癌患者术后辅助卡培他滨为基础化疗方案疗效的影响

摘 要：［目的］ 探讨胸苷脱氨酶（CDA）基因遗传变异对结直肠癌患者术后辅助卡培他滨为基础的化疗方案疗效及安全性的影响。［方法］ 纳入215例术后接受辅助化疗的结直肠癌患者。收集患者外周血提取DNA用来进行CDA多态性位点基因分型。另外,收集85例结直肠癌患者的化疗前外周血单核细胞（PBMC）提取RNA对CDA mRNA表达水平进行测定。对基因型和基线临床资料进行相关性分析。基因型和预后的单变量分析用Kaplan-Meier生存分析方法,并通过Cox风险比例模型对其他变量进行校正。［结果］ CDA基因启动子区域的多态性位点rs532545和疗效相关。rs532545位点在结直肠癌患者中的分布频率为：GG型157例（73.02%）,GA型53例（24.65%）,AA型5例（2.33%）,最小等位基因频率为0.15,三种基因型分布频率符合哈迪温伯格平衡（P=0.834）。预后比较将GA和AA型患者合并,对不同基因型患者进行预后分析发现,GA/AA和GG基因型患者的3年无疾病生存（DFS）率分别为81.03%和62.42%,差异具有统计学意义（P=0.002）。两种基因型患者的5年总生存（OS）率分别为72.41%和53.50%,差异具有统计学意义（P=0.016）。对DFS构建多变量的Cox模型校正之后GA/AA基因型对DFS的影响仍然具有统计学意义（OR=0.55,P=0.011）。另外,进一步在85例外周血单核细胞的mRNA表达分析中发现,携带A等位基因的患者相对于野生型GG型患者,外周血单核细胞中CDA的mRNA表达明显较高,并具有统计学意义（P<0.001）。［结论］ CDA基因rs532545位点可能通过影响该基因mRNA的表达进而使结直肠癌患者从卡培他滨的治疗当中获益。     

Expression of ERCC1, MSH2 and PARP1 in Non-small Cell Lung Cancer and Prognostic Value in Patients Treated with Platinum-based Chemotherapy

Purpose: To evaluate the prognostic value of the expression of excision repair cross-complementation groupl (ERCC1), MutS protein homolog 2 (MSH2) and poly ADP-ribose polymerase 1 (PARP1) in non-small-cell lungcancer patients receiving platinum-based postoperative adjuvant chemotherapy. Methods: Immunohistochemistrywas applied to detect the expression of ERCC1, MSH2 and PARP1 in 111 cases of non-small cell lung cancerparaffin embedded surgical specimens. Through og-rank survival analysis, we evaluated the prognostic valueof the ERCC1, MSH2, PARP1 and the related clinicopathological factors. COX regression analysis was used todetermine whether ERCC1, MSH2 and PARP1 were independent prognostic factors. Results: In the enrolled111 non-small cell lung cancer patients, the positive expression rate of ERCC1, MSH2 and RARP1 was 33.3%,36.9% and 55.9%, respectively. ERCC1 (P<0.001) and PARP1 (P=0.033) were found to be correlated with thesurvival time while there was no correlation for MSH2 (P=0.298). Patients with both ERCC1 and PARP1 negativecancer had significantly longer survival time than those with ERCC1 (P=0.042) or PARP1 (P=0.027) positivealone. Similalry, the survival time of patients with both ERCC1 and PARP1 positive cancer was shorter thanthose with ERCC1 (P=0.048) or PARP1 (P=0.01) positive alone. Conclusion: Patients with ERCC1 or PARP1negative non-small cell lung cancer appear to benefit from platinum-based postoperative adjuvant chemotherapy.     

Neutrophil-related Variables Have Different Prognostic Effect Based on Primary Tumor Location in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy

BackgroundClinical data reported a relationship between neutrophil-related variables and poor prognosis in patients with metastatic colorectal cancer (mCRC), but only platelet-to-lymphocyte ratio has been reported as prognostic.Patients and MethodsA retrospective analysis of 145 patients with mCRC, who received chemotherapy at the department of Oncology of the Ospedale Civile di Sanremo in 2010 to 2013, was performed, and a Cox model was built.ResultsIn the model, some variables were independently related with overall survival (OS) (resection of the primary tumor, number of drugs included in the first-line chemotherapy regimen), whereas neutrophil-related ones were not. However, after stratification by tumor location, neutrophil-related variables appeared associated with a poor survival among patients with a left-sided mCRC, and in particular, among those ones with a rectal tumor (hazard ratio, 3.732; 95% confidence interval, 1.575-8.845).ConclusionNeutrophil-related variables predicted outcome in patients with left-sided mCRC only. A high prevalence of consensus molecular subtype 4 CRC in patients with metastatic cancer of the rectum is suggested.     

ERCC1和XRCC3基因多态性在接受含铂方案化疗NSCLC中的疗效预测作用

[目的]探讨DNA修复基因ERCC1 118和XRCC3 241多态性对于接受一线含铂化疗方案的非小细胞肺癌（NSCLC）患者的疗效预测作用。[方法]130例晚期接受含铂化疗的NSCLC患者进入研究．应用Taqman探针结合实时荧光PCR方法分析其外周血基因多态性．分析ERCC1 118和XRCC3 241多态性与疗效、疾病进展时间和总体生存期之间的关系。[结果]130例患者的总体有效率为20％．中位生存时间为15个月．ERCC1 118和XRCC3 241多态性与疗效无显著相关性。ERCC1 118基因型C/T或T/T患者的生存时间显著延长（P=0.003）。Cox多因素分析显示,ERCC1 118基因型C/T或T/T以及化疗有效患者的生存期显著延长。[结论]DNA修复基因ERCC1 118基因型C／T或T/T多态性可以延长NSCLC患者铂类治疗后的生存时间．     

MTHFR C677T Polymorphism and Pancreatic Cancer Risk:a Meta-analysis

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate,and the role of the MTHFR C677T polymorphism in pancreatic carcinogenesis is still controversial. Method: Aliterature search was performed using Pubmed and CNKI databases for published studies through May 2012.We performed a meta-analysis of all relevant case-control studies that examined the association between MTHFRC677T polymorphism and pancreatic cancer risk. Results: Finally, 9 individual case-control studies with a totalof 1,299 pancreatic cancer cases and 2,473 controls were included into this meta-analysis. Results: This metaanalysisshowed there was an obvious association between MTHFR C677T polymorphism and pancreatic cancerrisk in East Asians (for allele model, OR = 1.67, 95%CI 1.11-2.51; For homozygote model, OR = 2.77, 95%CI1.40-5.48; for recessive model, OR = 1.96, 95%CI 1.54-2.50; for dominant model, OR = 2.11, 95%CI 1.01-4.41).However, no significant association was found in Caucasians. Conclusion: The MTHFR C677T polymorphismis associated with pancreatic cancer risk, and a race-specific effect may exist in this association. More studieswith a larger sample size are needed to further clarify this association.     

The Cyclin D1 G870A Polymorphism and Colorectal Cancer Susceptibility: A Meta-analysis of 20 Populations

Purpose: Studies of the association between the cyclin D1 (CCND1) G870A genetic polymorphism and riskof colorectal cancer (CRC) have generated conflicting results. In order to derive a more precise estimation, ameta-analysis was here performed. Materials and methods: An extensive search of relevant studies was carriedout as a meta-analysis of twenty studies with 5,975 cases and 8,333 controls. Results: Overall, a significantlyelevated colorectal cancer risk was associated with variant allele 870A when all studies were pooled (AA vs.GG: OR = 1.23, 95%CI = 1.04-1.44; GA vs. GG: OR = 1.13, 95%CI = 1.01-1.26; dominant model: OR = 1.16,95%CI = 1.03-1.31). In the subgroup analysis by ethnicity, significantly increased risks were detected amongCaucasians (AA vs. GG: OR = 1.27, 95%CI = 1.04-1.44; and dominant model: OR = 1.17, 95%CI = 1.02-1.34).With stratification into sporadic CRC and hereditary nonpolyposis colorectal cancer (HNPCC), the formerdemonstrated increased cancer susceptibility (AA vs. GG: OR = 1.24, 95%CI = 1.04-1.48; dominant model:OR = 1.17, 95%CI = 1.04-1.33). However, no significant associations were found in either Asians or HNPCCpatients for any genetic model. Conclusion: The results suggest that the cyclin D1 870A allele is a low-penetrantrisk factor for development of sporadic colorectal cancer, especially among Caucasians.     

The Exonuclease 1 Glu589Lys Gene Polymorphism and Cancer Susceptibility: Evidence Based on a Meta-analysis

Background: Published studies on the association between the exonuclease 1 (EXO1) Glu589Lys polymorphismand cancer susceptibility have yielded conflicting results. Thus, a meta-analysis of published studies was performedto assess the possible association. Materials and Methods: All eligible case-control studies published up to January2013 on the association between the EXO1 Glu589Lys polymorphism and cancer susceptibility were identified bysearching PubMed, Web of Science, Science Direct and hand search. Either fixed-effect or random-effect modelswere used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) using the ComprehensiveMeta-Analysis software version 2.2. Results: A total of 4,391 cancer cases and 4,339 controls from 10 studieswere included. Overall, no significant association between the EXO1 Glu589Lys polymorphism and cancersusceptibility was observed in either genetic model. However; in subgroup analyses by cancer type, a significantassociation between EXO1 Glu589Lys and lung cancer risk was found (Lys vs Glu: OR=1.23, 95%CI=1.07-1.41, pheterogeneity=0.05). Further, subgroup analysis by ethnicity indicated that there was a statistically increasedcancer risk in Asians (Lys vs Glu: OR=1.42, 95%CI=1.30-1.55, pheterogeneity=0.07; Lys/Lys vs Glu/Glu: OR=1.93,95%CI=1.20-3.12, pheterogeneity=0.01; Lys/Lys+Glu/Lys vs Glu/Glu: OR=1.52, 95%CI=1.37-1.68, pheterogeneity=0.42;Lys/Lys vs Glu/Lys+Glu/Glu: OR=1.68, 95%CI=1.07-2.65, pheterogeneity=0.02). However, significant association wasabsent in Caucasians. Conclusions: This meta-analysis suggests, for the first time, that the EXO1 Glu589Lyspolymorphism is not associated with overall cancer susceptibility, although marginal associations were found forlung cancer and Asian subgroups. Additional well-designed studies with larger sample size focusing on differentethnicities and cancer types are needed to confirm these findings.