CCND1基因870位点多态性同肿瘤遗传易感性关系的Meta分析

是其患肿瘤的一个遗传易感因素.     

细胞周期素D1 G870A基因多态性与胃癌易感性关系的Meta分析

摘 要：［目的］采用Meta 分析方法研究细胞周期素D1（CCND1）基因G870A多态性与胃癌易感性的关系。［方法］ 通过关键词与主题词检索PubMed,Ovid,CNKI,维普和万方数据库中有关CCND1基因G870A多态性与胃癌易感性的相关性研究,数据分析应用Review Manager 5.3和STATA 10.0 软件。［结果］ 纳入6篇文献,包括7个病例-对照试验研究,共计1283例胃癌患者为病例组与1760例非肿瘤患者为对照组。Meta分析结果显示,总人群中,CCND1基因G870A多态性与胃癌发生风险之间无显著相关性（A vs G：OR=0.90,95%CI：0.77～1.06,P=0.21;AA+AG vs GG：OR=0.85,95%CI：0.60～1.21,P=0.37;AG+GG vs AA：OR=1.15,95%CI：0.97～1.37,P=0.10）。在种族与肿瘤类型的亚组分层分析中,结果同样显示CCND1基因G870A多态性与胃癌的发生风险无明显相关性。［结论］ CCND1基因G870A多态性可能与胃癌的发生风险无关。     

OOND1基因870位点多态性同肿瘤遗传易感性关系的Meta分析

目的：综合评价细胞周期蛋白D1（Cyclin D1）基因CCND1的G870A多态性与肿瘤遗传易感性的关系。方法：以“CCND1、Cyclin D1、Bcl-1、polymorphism、cancer、细胞周期蛋白（素）D1、多态性和肿瘤”为关键词,检索Medline、EMBASE、Springerlink、Highwire、CBM、CNKI、维普和万方等中英文数据库,获得1991—01—2008—09有关CCND1基因G870A多态性同肿瘤易感性关系的研究结果。对所获文献进行质量评价、筛选和异质性检验,要求所纳入文献均为非相关的病例对照研究,均以0R值为效应指标,基因型在对照群体中的分布均符合Hardy—Weinberg遗传平衡定律。利用Rev Man4．2软件进行Meta分析。结果：共纳入26篇研究文献,累计病例7444例,对照11909例。A／G和A／A等位基因同G／G纯合子相比,0R值分别为1．10（95％CI：1．00～1．22）和1．34（95％CI：1．16～1．55）,对应的P值分别为0．06和〈0．0001。结论：CCND1 G870A能够增加携带者患肿瘤的发病风险,A／A基因型是其患肿瘤的一个遗传易感因素。     

细胞周期素D1 G870A基因多态性与头颈部肿瘤易感性的Meta分析

目的:探讨细胞周期素D1 G870A基因多态性与头颈部肿瘤易感性的关系。方法:通过计算机检索和手工检索,收集有关细胞周期素D1 G870A基因多态性与头颈部肿瘤易感性关系的文献,筛选出符合条件的文献,应用Meta分析软件对各项研究进行异质性检验,计算合并OR值及其95%可信区间,并行敏感性分析和发表偏倚的评估。结果:13篇文献纳入本研究,共计有2496例头颈部肿瘤患者和2463例对照人群。Meta分析合并结果显示与细胞周期素D1 G870A基因AA基因型比较,携带GG基因型和携带GG或GA基因型个体头颈部肿瘤发生风险的OR值分别为0.88和0.89(OR=0.88,95%CI:0.59-1.32;OR=0.89,95%CI:0.67-1.19)。通过种族的分层分析,没有发现细胞周期素D1 G870A基因多态性与头颈部肿瘤易感性在亚洲人群和欧洲人群中有差异。结论:细胞周期素D1 G870A基因多态性可能与头颈部肿瘤易感性间不存在明显相关性,但纳入研究的数量及每个研究的样本量均较少,需加大样本量进一步研究。     

细胞周期蛋白D1基因G870A 多态性与结直肠癌易感性的系统评价

 目的 综合评价细胞周期蛋白D1(Cyclin D1) 基因G870A多态性与结直肠癌易感性的关系.方法通过CNKI、PubMed、EMCC等数据库检索文献,获得有关Cyclin D1基因G870A多态性与结直肠癌危险性关系的研究结果,并通过Meta分析进行系统评价。所有文献均采用病例对照研究或者巢式病例对照研究,以OR值为效应指标, 基因型在对照群体中的分布均符合Hardy Weinberg 遗传平衡定律,对文献进行评价筛选、异质性检验。本次Meta分析共纳入23项研究,累计病例6 344例,对照9 018例,利用RevMan5.0对各研究原始结果进行统计处理, 对突变纯合子AA 和杂合子GA 基因型与纯合基因型GG 进行比较,并计算合并OR值及其95%可信区间(CI）。结果 AA和GA与GG基因型在病例组与健康对照组之间差异有统计学意义,OR= 1.10（95%CI：1.01～1.19, P=0.02）;按不同人群进行分层分析,亚洲人群OR= 1.11（95%CI：0.98～1.26, P=0.11）,美洲人群OR= 1.13（95%CI：0.97~1.32,P=0.12),欧洲人群OR= 1.06（95%CI：0.89～1.25, P=0.52）,大洋洲人群OR= 1.05（95%CI：0.80～1.38, P=0.73）;按不同对照进行分组分析,医院基础OR= 1.07（95%CI：0.95～1.20, P=0.28）,人群基础OR= 1.13（95%CI：1.01~1.26, P=0.04）。结论 Cyclin D1基因G870A 多态性与结直肠癌易感性总体分析在统计学上具有相关性,按不同人群进行分组分析,都不支持具有相关性;按不同对照进行分组分析,以医院基础不具有相关性,以人群为基础具有相关性。     

IL-10基因-592C>A多态性与宫颈癌易感性的Meta分析

目的:系统评估IL-10基因-592C>A多态性与宫颈癌易感性。方法:计算机检索Pubmed、EBSCO、Web of Science、中国知网、万方等数据库,搜集关于IL-10基因-592C>A多态性与宫颈癌易感性的相关研究文献。遵循文献纳入和排除标准,采用RevMan5.2软件进行Meta分析,计算、合并OR值及95%CI,最后进行偏倚分析和敏感性分析。结果:共纳入9篇文献,累计病例2 913例,对照2 037例。Meta分析结果显示,IL-10基因-592C>A多态性与宫颈癌总体发病风险之间未见显著关系(AA+CA vs CC:OR=0.92,95%CI=0.68~1.26,P=0.62;A vs C:OR=1.01,95%CI=0.82~1.23,P=0.95;AA vs CC:OR=1.04,95% CI=0.65~1.64,P=0.88;AA vs CA+CC:OR=1.08,95%CI=0.82~1.43,P=0.58;CA vs CC:OR=0.9,95%CI=0.67~1.19,P=0.45)。根据人群进行亚组分析结果显示,该基因多态性与亚洲人群及西方人群宫颈癌发病风险均无明显相关性（P>0.05）。结论:IL-10基因-592C>A多态性与宫颈癌易感性可能无关。     

CCND1 G/A位点基因多态性与肝细胞癌发生风险相关性的Meta分析

目的探讨细胞周期蛋白D1(CCND1)G/A位点基因多态性与肝细胞癌(HCC)发生风险的相关性。方法利用Pub Med、CNKI和EMbase数据库系统检索:CCND1 G/A位点基因多态性与肝细胞癌发生风险相关性的病例-对照研究。以病例组与对照组CCND1 G/A位点各种基因模型的比值比(OR)及95%可信区间(CI)为效应指标,并用Egger检验和Begg检验进行发表偏倚评价。结果有7项研究符合纳入标准。共纳入1108例肝癌患者和1477例对照。Meta分析结果表明:CCND1 G/A位点基因多态性与肝细胞癌发生风险无明显相关性,其中(AA vs GG:OR=1.33,95%CI:0.98~1.82,P=0.07;GA vs GG:OR=1.07,95%CI:0.92~1.24,P=0.37;GA+AA vs GG:OR=0.93,95%CI:0.82~1.05,P=0.23;AA vs GG+GA:OR=1.08,95%CI:0.95~1.22,P=0.24)。结论基于目前研究结果,尚不能认为CCND1 G/A位点基因多态性与肝细胞癌发生风险有显著相关性。     

XRCC1 Arg399Gln位点多态性与乳腺癌易感性的Meta分析

[目的]评估X射线交叉互补修复基因1(X-ray repair cross complementing protein 1,XRCC1)基因Arg399Gln位点单核苷酸多态性与高加索及亚洲人群乳腺癌(breast cancer,BC)易感性的关系。[方法]检索Pub Med、Embase、中国期刊全文数据库(CNKI)、万方数据库、中国生物医学文献数据库(CBM)和中文科技期刊全文数据库(VIP)等数据库,获取有关XRCC1 Arg399Gln位点多态性与高加索及亚洲人群乳腺癌易感性关系的病例对照研究的资料,以病例组及对照组XRCC1 Arg 399Gln等位基因分布的比值比(OR)为效应指标,应用Meta分析软件Review Manager(version 5.0.10)对各研究原始数据进行统计处理及异质性检验,计算合并OR值及其95%可信区间。[结果 ]共纳入24项病例对照研究,包括15151例乳腺癌患者和17179例对照。Meta分析结果显示,XRCC1 Arg399Gln位点Gln/Gln突变型可能会增加亚洲人群乳腺癌的发病风险[Gln/Gln vs.Arg/Arg亚洲组:OR=1.20(95%CI:1.03~1.39),P=0.02;Gln/Gln vs.Arg/Arg+Arg/Gln亚洲组:OR=1.20(95%CI:1.04~1.38),P=0.01。Gln/Gln vs.Arg/Arg OR=1.01(95%CI:0.94~1.09),Z=0.35,POR=0.73;Gln/Gln+Arg/Gln vs.Arg/Arg OR=1.02(95%CI:0.95~1.09,Z=0.58,POR=0.56;Gln/Gln vs.Arg/Arg+Arg/Gln OR=1.01(95%CI:0.95~1.08),Z=0.33,POR=0.74)。[结论]XRCC1 Arg399Gln位点Gln/Gln突变型可能与亚洲人群乳腺癌易感性相关。     

CYP1A1和GSTM1基因多态性与肺癌易感性的Meta分析

目的探讨CYP1A1和GSTM1基因多态性与个体肺癌易感性的关系。方法全面检索相关文献,应用Meta分析方法对各研究进行数据的合并与分析。结果共8篇文献入选,累计肺癌病例1067人,对照1416人,分别对CYP1A1*A和GSTM1-、CYP1A1*B/C和GSTM1+、CYP1A1*B/C和GSTM1-联合基因型进行统计分析。异质性检验χ2值分别为6.43、8.83与9.63,P>0.05,文献有同质性,各合并OR及95%CI分别为1.36(1.09~2.77)、1.65(1.26~2.15)和2.01(1.57~2.59)。结论CYP1A1和GSTM1突变基因型为罹患肺癌的易感基因型,且两者存在协同作用,在肿瘤防治方案中应加以重视从而采取相应措施达到有效预防肿瘤的目的。     

EPHX1 A415G基因多态性与胃肠道肿瘤易感性的Meta分析

目的 探讨微粒体环氧化物水解酶（EPHX1）A415G基因多态性与胃肠道肿瘤易感性的关系。方法 计算机检索PubMed、EMBASE、CBM、维普、万方及中国知网数据库,检索时间截至2013年5月,收集关于EPHX1 A415G基因多态性与胃肠道肿瘤易感性的研究。由2名评价者按照纳入和排除标准独立选择文献、提取资料、评价质量。采用STATA 110软件进行Meta分析,计算合并OR值及其95％CI并行敏感性分析和发表偏倚的评估。结果 最终纳入18篇文献,包括5852例胃肠道肿瘤患者和8710例对照人群。纳入的结果在GG vs. AA、GA vs. AA、GG/GA vs. AA和GG vs. GA/AA基因型的比较模型中均无异质性。各遗传模型Meta分析结果显示,EPHX1 A415G基因多态性与胃肠道肿瘤遗传易感性的关联性无统计学意义［GG vs. AA： OR=1.063,95％CI： 0.888～1.273;GA vs. AA： OR=0.935,95％CI： 0.867～1.009;GG/GA vs. AA： OR=0.948,95％CI： 0.882～1.020;GG vs. GA/AA： OR=1.091,95％CI： 0.913～1.304］。结论 EPHX1 A415G基因多态性与胃肠道肿瘤易感性之间无明显相关性。     

Specific CCND1 G870A Alleles Associated with Breast Cancer Susceptibility: a Meta-analysis of 5,528 Cases and 5,353 Controls

Background: The Cyclin D1(CCND1) G870A polymorphism may be associated with breast cancer, but theevidence from individual studies is inconclusive. The aim of this study was to investigate the correlation betweenthe CCND1 G870A polymorphism and breast cancer risk in a meta-analysis. Materials and Methods: Wesearched Pubmed and analysed 11 articles on 5,528 cases and 5,353 controls before February 1, 2012. Results:we found there are significant association for AA versus GG and AA versus GA/GG. No significant associationswere found for GA versus GG, GA/AA versus GG. There are significant association for AA versus GG ,and AAversus GA/GG in Caucasians. We didn’t find any significant main effects for G870A polymorphism on breastcancer risk either in recessive or dominant models in Asians. Conclusion: This meta-analysis suggests that AAof the CCND1 G870A polymorphism is associated with breast cancer susceptibility.     

Cyclin D1 A870G polymorphism and the risk of colorectal cancer and adenoma

Cyclin D1 (CCND1) plays a key role in cell cycle control, particularly in the transition from G1 to S phase, which is regulated by cyclin-dependent kinases. A common adenine to guanine polymorphism (A870G) in the CCND1 gene has been associated with a longer-life protein and an increased risk of colorectal cancer and adenoma in some studies. Among subjects with hereditary nonpolyposis colorectal cancer, the A870G polymorphism has also been associated with a younger age of onset of colorectal cancer. We analysed 181 colorectal cancer cases and 475 matched controls and 524 adenoma cases and 517 matched controls within women in the Nurses' Health Study (NHS) cohort, 171 colorectal cancer cases and 347 matched controls and 372 adenoma cases and 712 matched controls nested within men in the Health Professionals' Follow-Up Study (HPFS) cohort, and 258 colorectal cancer cases and 415 matched controls within men in the Physicians' Health Study (PHS) cohort to assess the risk associated with the CCND1 A870G genotype. Moreover, we assessed whether CCND1 genotype modified the effect of a sporadic (nonsyndromic) family history of colorectal cancer as well as the effect of other dietary and lifestyle risk factors for colorectal cancer and adenoma. In all cohorts combined, the CCND1 polymorphism did not show statistically significant associations to risk of colorectal cancer (odds ratio (OR) for A allele carriers, 1.04; 95% confidence interval (95% CI), 0.82-1.32) or adenoma (OR, 0.96; 95% CI, 0.79-1.18). The CCND1 A870G genotype was associated with a modest, although nonsignificantly elevated risk of colorectal cancer (OR, 1.59; 95% CI, 0.98-2.57) in women. In contrast, the polymorphism was not associated with increased risk of adenoma in either men or women. Among participants with the A870G genotype, a family history of colorectal cancer conferred a substantially greater risk of colorectal cancer in the women (P for interaction=0.06) and adenoma in the men (P for interaction=0.02). Current postmenopausal hormone (PMH) use was associated with a significant reduction in the risk of colorectal cancer and adenoma among women with the A870G genotype, whereas there was no effect of PMH use among those with the GG genotype. The CCND1 polymorphism appeared to confer a modest elevation in the risk of colorectal cancer among women. Moreover, the A870G genotype may enhance the protective effect of postmenopausal oestrogen use on the development of colorectal neoplasia.     

The CCND1 G870A Gene Polymorphism and Leukemia or Non-Hodgkin Lymphoma Risk: a Meta-analysis

In recent years, mounting evidence has indicated that the CCND1 G870A gene polymorphism, which impacts the mitotic cell cycle, may influence leukemia or non-Hodgkin lymphoma risk. Unfortunately, the previous results were inconsistent. Therefore, a meta-analysis was performed to obtain a more precise estimation of any association. We conducted a search in PubMed, Embase and CNKI covering all published papers up to March, 2014. A total of 9 publications including 10 case-control studies met the inclusion criteria. Odds ratios (ORs) and their 95% confidence intervals (95%CIs) were applied to assess association. The pooled ORs showed significant association in non-Hodgkin lymphoma (comparison A vs G: OR= 1.114, 95%CI=1.053-1.179, p=0.000; homozygote comparison AA vs GG: OR=1.245, 95%CI=1.110-1.396, p=0.000; heterozygote comparison AG vs GG: OR=1.095, 95%CI=1.000-1.199, p=0.05; dominant model AA/GA vs GG: OR=1.137, 95%CI=1.043-1.239, p=0.003; and recessive model AA vs GA/GG: OR=1.177, 95%CI=1.066-1.301, p=0.001). However, there was no association between the CCND1 G870A polymorphism and leukemia risk. In conclusion, the CCND1 G870A polymorphism may increase risk of non-Hodgkin lymphoma, but not leukemia. However, more primary large scale and well-designed studies are still required to evaluate the interaction of CCND1 G870A polymorphism with leukemia and non-Hodgkin lymphoma risk.     

<Emphasis Type="Italic">CCND1</Emphasis> G870A polymorphism contributes to breast cancer susceptibility: a meta-analysis

Cyclin D1 (CCND1), a key cell cycle regulatory protein that governs the cell cycle progression from G1 to S phase, can promote cell proliferation or induce growth arrest and apoptosis. Since the identification of a well-characterized functional polymorphism, G870A in exon 4 of CCND1, several molecular epidemiological studies were conducted in recent years to evaluate the association between G870A and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis on 5,371 cases with breast cancer and 5,336 controls from 7 published case-control studies showed that the variant allele 870A was associated with a significantly increased risk of breast cancer (AA vs. GG: OR = 1.18, 95% CI = 1.06–1.32; AG vs. GG: OR = 1.12, 95% CI = 1.01–1.23; AA/AG vs. GG: OR = 1.14, 95% CI = 1.04–1.25) without any between-study heterogeneity. In the stratified analysis by race, we found that the increased breast cancer risk associated with G870A polymorphism was more evident in Caucasians (OR = 1.14, 95% CI = 1.01–1.28, P = 0.88 for heterogeneity test), but not significant in Asians (OR = 1.10, 95% CI = 0.85–1.42, P = 0.05 for heterogeneity test). The results suggest that CCND1 G870A polymorphism may contribute to breast cancer development, especially in Caucasians. Additional well-designed large studies were required for the validation of this association in different populations. Cheng Lu and Jing Dong contributed equally to this work.     

Methylenetetrahydrofolate reductase C677T polymorphism and cervical cancer risk: a meta-analysis

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate,and the role of MTHFR C677T polymorphism in cervical carcinogenesis is still controversial. Method: Weperformed a meta-analysis of all relevant case-control studies that examined any association between the C677Tpolymorphism and cervical cancer risk. We estimated summary odds ratios (ORs) with their confidence intervals(CIs) to assess links. Results: Finally, 10 studies with a total of 2113 cervical cancer cases and 2804 controls wereincluded. Results from this meta-analysis showed that significantly elevated cervical cancer risk was associatedwith the MTHFR T allele in the Asian population under conditions of two genetic comparison models (for TTvs. CC, OR = 1.37, 95%CI 1.00-1.87, P = 0.050; for TT vs. TC+CC: OR = 1.34, 95%CI 1.01-1.77, P = 0.039).However, there was no obvious association between the MTHFR C677T polymorphism and cervical cancer riskin the other populations. Conclusion: The MTHFR C677T polymorphism is associated with cervical cancer riskin Asians, while any possible link in the Caucasian population needs further studies.     

CCND1 G870A polymorphism and risk for head and neck cancer: a meta-analysis

CCND1 plays a critical role in cell cycle control and may contribute to head and neck cancer. We performed a meta-analysis of eleven case–control studies that examined the association between CCND1 G870A polymorphism and head and neck cancer risk. Overall, no significant association of this polymorphism with head and neck cancer was found (for AA vs. GG: OR = 0.96, 95% CI = 0.59–1.58, P < 0.01 for heterogeneity; for GA vs. GG: OR = 1.00, 95% CI = 0.74–1.35, P < 0.01 for heterogeneity; for the dominant model GA/AA vs. GG: OR = 0.98, 95% CI = 0.69–1.39, P < 0.01 for heterogeneity; for the recessive model AA vs. GG/GA: OR = 0.94, 95% CI = 0.66–1.33, P < 0.01 for heterogeneity). In subgroup analysis by ethnicity, we also did not find any significant association in European and Asians populations. All the results were not materially altered in any genetic model after the studies which did not fulfill Hardy–Weinberg equilibrium were excluded. In conclusion, our meta-analysis strongly suggested that the CCND1 G870A polymorphism is not associated with head and neck cancer risk.