凋亡通路Fas/Fasl遗传变异与胃癌发病风险的关系

目的凋亡通路Fas/Fasl在肿瘤的发生发展中起着重要作用,本文探讨Fas/Fasl遗传变异与胃癌易感性的关系。方法以聚合酶链反应-限制性片段长度多态性对218例胃癌患者和218例正常对照进行基因分型,以logistic回归的比值比（OR）及其置信区间（CI）来评估风险度。结果携带Fasl-844TC或CC基因型个体患胃瘤的发病风险均无显著性差异（OR=0.82,95%CI=0.38-1.79;OR=1.84,95%CI=0.86-3.95）。而携带Fas-1377AA基因型的个体胃癌发病风险显著增加,OR为2.13（95%CI=1.15-3.94）。联合作用与交互作用分析发现既携带Fas-1377AA又携带Fasl-844CC基因型的个体发生胃癌的OR增加到4.43（95%CI=1.85-10.62）,且Fas-1377G/A多态与Fasl-844T/C多态存在显著相乘交互作用（P=2.02×10-5）。结论 Fas–1377G/A遗传变异可增加胃癌发病风险,Fas–1377G/A与Fasl-844T/C联合与相乘交互作用共同增加胃癌发病风险。     

survivin基因启动子区-31C/G多态性与散发性结直肠癌遗传易感性的关系

目的： 探讨生存素survivin基因启动子区-31C/G单核苷酸多态性与中国华南地区散发性结直肠癌（CRC）易感性的关系。 方法: 采用聚合酶链反应-限制性片段长度多态性法（PCR-RFLP）检测华南地区711例健康人和702例CRC的survivin基因-31C/G位点单核苷酸多态性。结果: 结直肠癌患者CC基因型的频率明显高于对照人群（36.5% vs 26.2 %,2=17.89,P<0.01）,与CC基因型相比,CG、GG基因型和等位基因G携带者的CRC发病风险分别显著下降至0.61倍（95%CI=0.46-0.80,P<0.01）、0.52倍（95%CI=0.38-0.71,P<0.01）和0.58倍（95%CI=0.45-0.74,P<0.01）。结论: survivin基因-31C/G多态与CRC发病风险有关,-31G变异基因型是中国南方人群散发性结直肠癌独立保护因素。     

儿童脓毒症纤溶酶原激活物抑制剂-1基因启动子区4G/5G多态性的研究

目的探讨纤溶酶原激活物抑制剂-1（PAI-1）基因启动子区单核苷酸插入或缺失（4G/5G）多态性与广州地区汉族脓毒症患儿的相关性,对脓毒症的发生、发展和临床预后的影响。方法选取2007年4-12月广州市妇女儿童医疗中心诊治的汉族脓毒症患儿为病例组,同期收集健康查体儿童为对照组。应用等位基因特异性扩增多聚酶链（AS-PCR）法对病例组和对照组行PAI-1基因启动子区4G/5G多态性检测和分析。采用基因计数法计算各组基因型频率和等位基因频率,χ^2检验分析比较两组人群各基因型的分布差异,计算OR值及其95%CI评估各基因型的风险。结果研究期间病例组纳入148例,对照组181名。病例组和对照组PAI-1基因启动子区4G/5G多态性的基因型和等位基因频率分布差异无统计学意义（χ^2=0.79,P〉0.05）。等位基因4G（χ^2=4.35,P〈0.05）及其纯合子（χ^2=4.44,P〈0.05）与脓毒症发展相关;携带等位基因4G患儿发展至重症脓毒症的风险比5G高,OR=4.05（95%CI：1.09-15.08）,4G/4G纯合子患儿发展至重症脓毒症的风险比其他基因型高,OR=4.57（95%CI：1.11-18.78）。等位基因4G（χ^2=9.17,P〈0.05）及其纯合子（χ^2=7.35,P〈0.05）与脓毒症病死率相关,携带等位基因4G患儿脓毒症病死风险较5G高,OR=4.30（95%CI：1.50-12.29）,4G/4G纯合子患儿脓毒症病死风险较其他基因型高,OR=3.14（95%CI：1.49-6.61）。结论PAI-1基因启动子区4G/5G多态性与广州地区汉族脓毒症患儿进展及预后相关,等位基因4G及其纯合子是其高危遗传因素;PAI-1基因启动子区4G/5G点多态性与脓毒症的易感性无关。     

RET基因调控区遗传变异与先天性巨结肠患病风险研究

目的先天性巨结肠（HSCR）是一种复杂的先天性疾病,RET是其主要的易感性基因。本研究对RET非编码区单核甘酸多态性（SNP）-5G〉A（rs10900296）,-1A〉C（rs10900297）和intron1 C〉T（rs2435357）进行分型分析,评估RET基因调控区SNPs及单倍型与先天性巨结肠之间的相关性。方法选取115名病例组病人和139名对照组正常人群,应用聚合酶链反应（PCR）技术和直接测序的方法进行基因分型。回归模型中使用OR值和95%置信区间（CI）作为基因型危险性的评价指标。结果 -5G〉A,-1A〉C,intron1C〉T各基因型频率在病例和对照人群的分布具有显著差异。-5 AA（OR=6.26,95%CI=3.62-10.83）,-1 CC（OR=7.54,95%CI=2.06-27.66）和intron1 TT（OR=19.22,95% CI=7.54-48.99）基因型均能显著增加HSCR发病的风险。单倍型A-C-T（OR=6.28,95% CI=3.77-10.46）和双体型A-C-T/A-C-T（OR=13.62,95% CI=3.48-53.30）分析同样表明与HSCR发病风险存在较强的相关性,并呈现出一定的累积效应。结论 RET基因调控区的基因多态性可能与HSCR的发病易感性有关,支持RET通路的常见变异在HSCR的发展过程中起着重要的作用的假设。     

CyclinA2基因多态性与肝细胞肝癌易感性的关系

目的 探讨CyclinA2启动子区单核苷酸多态性与肝细胞肝癌发病风险的关系。方法 选取2012年10月~2017年9月在九江市第一人民医院确诊的原发性肝细胞肝癌患者180例,同时选择行体检的健康志愿者180例作为对照组。分别采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对cyclinA2基因的rs769236位点进行多态性检测,比较不同基因型与原发性肝细胞癌发病风险的关系。结果 rs769236 等位基因A（GA+AA）携带者患原发性肝细胞癌的风险显著高于rs769236GG野生基因型的个体（校正OR=1.825,95%CI=1.133-2.940）。结论 CyclinA2基因rs769236（G/A）位点A变异可能会增加原发性肝细胞癌的发病风险。     

环氧化酶-2功能性遗传变异与子宫内膜异位症遗传易感性的关系

目的探讨COX-2基因启动子区的单核苷酸多态位点与子宫内膜异位症遗传易感性的关系。方法采用蛋白酶K消化-饱和酚氯仿法提取外周血白细胞DNA,聚合酶链反应-限制性片段长度多态分析(PCR-RFLP)进行基因分型和序列测定。结果对照组和病例组COX-2-1195GG、AG和AA基因型频率分别是24·6%、53·3%和22·1%及14·2%、50·0%和35·8%(P<0·05)。两组中AG基因型频率无显著差异,而AA基因型频率有显著差异(P<0·05)。病例组A等位基因的频率显著高于对照组,携带一个A等位基因的患病风险为1·63,携带2个A等位基因的患病风险则为2·82,提示-1195A等位基因显著增加子宫内膜异位症的发病风险。结论COX-2基因启动子区的-1195G>A单核苷酸多态与子宫内膜异位症有关,可能是决定子宫内膜异位症个体遗传易感性的重要因素。     

PTPN11第3内含子基因多态性及H.pylori感染与广西柳州地区胃癌易感性研究

目的探讨蛋白酪氨酸磷酸酶非受体型11（PTPN11）基因多态性及幽门螺杆菌（H.pylori）感染与广西柳州地区胃癌易感性的相关性。方法通过PCR检测H.pylori的尿素酶B亚单位（UreB）基因和两步法聚合酶链反应（PCR-CTPP）对广西柳州地区238例胃癌患者及112例健康对照者的PTPN11基因第3内含子2460位点进行单链构象多态性分析（SNP）。结果胃癌组和对照组H.pylori（＋）者分别为142例（59.7%）和54例（48.2%）,H.pylori（-）者分别为96例（40.3%）和58例（51.8%）,H.pylori感染率在两组间差异有统计学意义（P〈0.05）。胃癌组和对照组PTPN11基因在该位点的基因型频率分布符合遗传平衡状态且差异无统计学意义（P〉0.05）,但两组间的等位基因分布差异有统计学意义（P〈0.05）。与G/G型相比,G/A型和A/A型不能减低胃癌的发病风险（G/A型：OR=0.642,95%CI：0.397～1.039;A/A型：OR=0.399,95%CI：0.097～1.641）;但将G/A型和A/A型合并后与G/G型相比,带有A基因的个体患胃癌的风险显著降低（OR=0.620,95%CI：0.388～0.992）。根据发病年龄、性别、吸烟史、饮酒史和H.pylori感染对胃癌的易感性进行的分层分析发现,PTPN11基因该位点SNP与胃癌的年龄、性别、吸烟史以及饮酒史无关,H.pylori阳性的A基因携带者相对于G/G型个体患胃癌的风险减少到0.52倍（OR=0.521,95%CI：0.274～0.990）。结论广西柳州地区PTPN11基因第3内含子2460位点A基因携带者能明显降低胃癌的发病风险,H.pylori感染与该位点G/G基因型之间存在交互作用。     

parkin基因启动子区－258T/G多态性与广西散发性帕金森病的相关性分析

【摘要】 目的：探讨广西地区parkin基因启动子区-258T/G多态性与散发性帕金森病（Sporadic Parkinson,s disease, SPD）的相关性及该多态性与PD发病年龄的关系。方法：应用聚合酶链式反应（PCR）、限制性片段长度多态性（RFLP）及DNA测序等技术,分析广西地区parkin基因-258T/G多态性在PD患者和健康对照者间分布频率的差异。结果：PD组parkin基因-258T/G多态性位点G等位基因频率显著高于正常对照组（55.20％ vs 43.33％,χ2=6.898,p＜0.05,OR=1.61,95%CI:1.13～2.30）;GG基因型频率显著高于对照组（28.00 % vs 18.33%）;（χ2=7.159,p＜0.05,OR=2.75,95%CI:1.31～5.77）。进一步将PD组按发病年龄分层发现, 50岁及50岁以上发病患者G等位基因频率显著高于对照组（58.12％ vs 43.33％ ,χ2＝8.404,p＜0.01,OR=1.82,95%CI:1.21～2.73）。GG基因型频率与对照组间差异亦有统计学意义（32.50% vs 18.33%,χ2＝8.517,p＜0.01,OR=3.45,95%CI:1.50～7.93）同时,PD组TG+GG基因型频率亦显著高于对照组（82.40% vs 68.33%,χ2＝6.551,p＜0.05,OR=2.17,95%CI:1.20～3.93）。50岁以下发病患者G等位基因频率及GG、TG+GG基因型频率虽高于正常对照组但差异无统计学意义。结论：Parkin基因核心启动子区-258T/G多态G等位基因可能增加了广西地区散发性PD发病风险,且与PD发病年龄成正相关。     

维生素D受体基因多态性与维生素D缺乏性佝偻病遗传关联性Meta分析

目的评价维生素D受体（VDR）基因多态性与维生素D缺乏性佝偻病（佝偻病）的遗传关联性。方法制定原始文献的纳入标准及检索策略,检索PubMed、Springer、Science Direct、Web of Science、中国期刊全文数据库、维普中文科技期刊数据库和万方数据库,收集VDR基因FokⅠ、ApaⅠ、BsmⅠ和TaqⅠ位点多态性与佝偻病相关性的病例对照研究,以佝偻病患儿为病例组。依据NHI-NHGRI研究工作组2007年制定的遗传关联性研究报告规范为基础,并依据相关文献选取其中的14条标准用于评价文献偏倚。以基因型频率为指标,提取数据后先确定最佳遗传模型,采用Stata 11.0软件进行Meta分析,计算合并的OR值及其95%CI。结果 19篇病例对照研究进入Meta分析。①FokⅠ位点采用共显性模型（FF基因型vsff基因型;FF基因型vsFf基因型）分析,病例组704例,对照组596例。Meta分析结果显示,亚洲人群FF基因型较ff基因型（OR=4.59,95%CI：2.98~7.07）和Ff基因型（OR=2.58,95%CI：1.79~3.73）患佝偻病的风险显著增加;高加索人群FokⅠ位点与佝偻病无显著关联性（FF基因型vsff基因型,OR=2.50,95%CI：0.76~8.19;FF基因型vsFf基因型,OR=1.18,95%CI：0.66~2.10）;非洲人群FF基因型较ff基因型患佝偻病的风险显著增加（OR=5.81,95%CI：1.21~27.98）。②ApaⅠ位点采用显性模型（AA＋Aa基因型vsaa基因型）分析,病例组338例,对照组459例。亚洲人群和非洲人群ApaⅠ位点与佝偻病均无显著关联性,OR分别为1.04（95%CI：0.72~1.49）和0.98（95%CI：0.57~1.71）;高加索人群AA＋Aa基因型患佝偻病的风险增高（OR=5.50,95%CI：1.22~24.75）。③BsmⅠ位点采用显性模型（bb基因型vsBb＋BB基因型）分析,病例组822例,对照组736例。亚洲人群BsmⅠ位点bb基因型较Bb＋BB基因型患佝偻病的风险降低（OR=0.46,95%CI：0.23~0.92）,非洲人群BsmⅠ位点与佝偻病无显著关联性（OR=1.65,95%CI：0.95~2.88）。④TaqⅠ位点采用隐性模型（TT基因型vsTt＋tt基因型）分析,病例组519例,对照组513例。亚洲人群（OR=1.22,95%CI：0.82~1.82）、高加索人群（OR=0.91,95%CI：0.35~2.35）和非洲人群（OR=1.18,95%CI：0.68~2.05）TaqⅠ位点与佝偻病无显著关联性。结论现有证据表明,亚洲人群FokⅠ位点FF基因型为患佝偻病的危险因素,而BsmⅠ位点bb基因型为佝偻病轻微的保护因素,尚不能认为ApaⅠ和TaqⅠ位点与佝偻病有关联性;由于高加索人群和非洲人群研究较少,VDR基因多态性与佝偻病的关联性尚不明确。     

CASP3和 CASP9基因多态性与胃癌遗传易感性的关联研究

目的 探讨凋亡相关基因caspase 3 (CASP3)、caspase 9 (CASP9)单核苷酸多态性与胃癌遗传易感性的关系.方法 采用以自然人群为基础的病例对照研究设计,对278例胃癌患者和以同年龄(± 5岁)、同性别、同居住地匹配为原则获得的278名对照进行研究.CASP3 rs12108497和 CASP9 rs4646018多态位点的基因分型采用聚合酶链反应-限制性片段长度多态性的方法分析.非条件Logistic回归分析计算基因多态与胃癌风险的相关性.结果 携带 CASP3 rs12108497 TC、CC基因型者患胃癌的风险较TT基因型者分别增加45%(OR=1.45,95%CI:1.01～2.07)和117% (OR=2.17,95%CI:1.15～4.08).未发现 CASP9 rs4646018基因多态与胃癌发病风险间存在显著关联.多基因模型显示携带1个或2个风险基因型的个体胃癌易感性增高(OR=1.60,95%CI:1.12～2.30).分层分析表明,携带1个或2个风险基因型的个体罹患胃癌的危险度在男性个体(OR=1.62,95%CI:1.05～2.49)、吸烟者(OR=1.87,95%CI:1.12～3.12)、饮酒者(OR=1.92,95%CI:1.02～3.65)和无肿瘤家族史者(OR=1.78,95%CI:1.18～2.68)中尤为明显.结论 CASP3 rs12108497 多态性会增加胃癌的发病风险.CASP9 rs4646018多态性与胃癌发病风险无关.

Abstract：

Objective To investigate the association between the apoptosis genes CASP3 (rs12108497) and CASP9 (rs4646018) polymorphisms and the risk of developing stomach cancer. Methods In this population-based case-control study, 278 cases with stomach cancer and 278 age (±5 years), gender, and residential area matched controls were recruited. The genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The unconditional Logistic regression analysis was utilized to calculate the odds ratios (OR) and 95% confidence intervals (CI). Results The individuals with TC, CC genotypes of rs12108497 locus had significantly increased risk of stomach cancer in comparison to those carrying TT genotype (OR=1.45, 95% CI: 1.01-2.07 for TC; OR=2.17, 95%CI: 1.15-4.08 for CC). However, the rs4646018 locus of CASP9 gene polymorphism was not related to stomach cancer risk. Compared with the subjects carrying the both low-risk genotypes, those carrying 1 or 2 high-risk genotypes had a noteworthy increased risk of stomach cancer (OR=1.60, 95% CI: 1.12-2.30). The combined high-risk genotypes appeared to be more evident in subjects of male (OR=1.62, 95% CI: 1.05-2.49), ever-smokers (OR=1.87, 95%CI: 1.12-3.12), ever-drinkers (OR=1.92, 95%CI:1.02-3.65) and no family history of cancer (OR=1.78, 95%CI: 1.18-2.68). Conclusion The current findings suggest that the polymorphism of CASP3 rs12108497 might be associated with the risk of stomach cancer. However, the CASP9 rs4646018 polymorphism may not be related to the stomach cancer risk.     

Cyclooxygenase-2 Polymorphisms and Susceptibility to Colorectal Cancer: A Meta-Analysis

Purpose

Four polymorphisms, -765G>C, -1195G>A, 8473T>C, and Val511Ala, in the cyclooxygenase-2 (COX-2) gene were identified to be associated with colorectal cancer (CRC) risk. However, the results are inconsistent. The objective of this meta-analysis was to evaluate the association between these four polymorphisms and the risk of CRC.

Materials and Methods

All eligible case-control studies published up to December 2012 on the association between the four polymorphisms of COX-2 and CRC risk were identified by searching PubMed and Web of Science. The CRC risk associated with the four polymorphisms of the COX-2 gene was estimated for each study by odds ratio (OR) together with its 95 % confidence interval (CI), respectively.

Results

A total of 15 case-control studies were included. Overall, no evidence has indicated that the -1195A allele, -765C allele, 8473C allele, and 511Ala allele are associated with susceptibility to CRC (-1195G>A: OR=1.11, 95 % CI: 0.82-1.51, p=0.78; -765G>C: OR=1.08, 95 % CI: 0.96-1.21, p=0.07; 8473T>C: OR=1.03, 95 % CI: 0.89-1.18, p=0.91; Val511Ala: OR=0.71, 95 % CI: 0.46-1.09, p=0.94). However, stratified analysis with ethnicity indicated that individuals with -765GC or GC/CC genotypes had an increased risk of CRC among Asian populations (GC vs. GG: OR=1.05, 95 % CI: 0.87-1.28, p=0.03; GC+CC vs. GG: OR=1.08, 95 % CI: 0.96-1.21, p=0.07).

Conclusion

This meta-analysis indicated that -765G>C polymorphism was significantly associated with susceptibility to CRC in Asian populations.     

The Cox-2 -1195 G > A polymorphism and cancer risk: a meta-analysis of 25 case-control studies

Cyclooxygenase 2 (Cox-2, a rate-limiting enzyme in the conversion of arachidonic acid to prostanoids) has been implicated in several physiological and pathological processes, and it has been reported that polymorphisms in the regulatory region of Cox-2 might influence its expression, contributing to the interindividual susceptibility to cancer. However, results from published studies on the association between the Cox-2 -1195G > A polymorphism and the risk of cancer are conflicting. We performed a meta-analysis based on 25 case-control studies, including a total of 9482 cancer cases and 12?206 controls to derive a more precise estimation of the association and its possible influence on cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The overall results indicated that the variant genotypes moderately increased risk of cancer (AA/AG versus GG, OR = 1.15, 95% CI: 1.02-1.31). In the stratified analysis for the -1195G > A polymorphism, a proximate association was observed in Asian populations (AA/AG versus GG, OR = 1.28, 95% CI: 1.12-1.46), but no significant association except for oesophageal cancer and 'others' was found when stratified by cancer type. In conclusion, our meta-analysis indicates that -1195G > A of Cox-2 is a low penetration risk factor for cancer.     

脂氧素A4抑制内毒素诱导的人支气管上皮细胞环氧合酶2及前列腺素E2的表达

目的: 探讨脂氧素A₄对人支气管上皮细胞(HBECs)环氧合酶2(COX-2)表达的影响。方法: 应用不同浓度(0.1、1、10 mg/L)的内毒素(LPS)刺激HBECs 9 h,或者用1 mg/L LPS分别刺激HBECs不同时点(3 h、6 h、9 h)后,测定HBECs的COX-2 mRNA表达和细胞上清液前列腺素E₂(PGE₂)水平。应用不同浓度 (0、100、400 μmol/L) 的脂氧素A₄作用于经过LPS(1 mg/L)刺激培养9 h的HBECs,采用酶联免疫吸附法(ELISA)检测细胞上清液PGE₂的水平, 同时分别应用RT-PCR和Western blotting分别检测HBECs COX-2 mRNA及蛋白的表达。结果: LPS刺激培养条件下HBECs的COX-2 mRNA表达及其上清液PGE₂水平增加,并呈时间、剂量依赖性。脂氧素A₄能抑制LPS刺激培养HBECs COX-2蛋白和mRNA的表达及上清液PGE₂的水平,并呈剂量依赖性。结论: 脂氧素A₄能抑制LPS诱导的HBECs COX-2表达及上清液PGE₂的水平。     

IL-6-174G／C多态性与肺癌无相关性：基于2901例肺癌患者和3234例对照的Meta分析

目的为准确评估IL-6-174G／C多态性与肺癌危险度的关系。我们采用了Meta分析的方法。通过检索Medline、EMBASE、OVID和中国生物医学数据库中至2012年12月为止发表的所有病例对照研究文献,筛选数据,计算合并的OR值和95％可信区间（95％CI）。最终纳人5篇文献,包括病例2901例,对照3234例。meta分析后发现,IL-6-174C等位基因并不能明显升高肺癌危险度（CCvs．GG：OR=1.06,95％CI=0．92-1．23;GCVS．GG：OR=1．05,95％CI=0．83～1．32;CC＋GCVS．GG：OR=1．01,95％CI=1．90-1．13;CCVS．GC＋GG：OR=1．08,95％CI=0．95～1．23）。漏斗图和Egger＇s检验没有发现发表偏倚,肺癌病理学和吸烟状态亚组分析示：IL-6-174G／C多态性与肺癌危险度无明显相关性。尽管存在一些局限,确切评估IL-6-174G／C与肺癌的危险度,有待于今后设计更好,样本量更大的研究。     

Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson’s disease susceptibility in Chinese Han population

Objective: The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinson’s disease (PD) susceptibility in Chinese Han population. Methods: The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using χ² test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. Results: On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). Conclusions: COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association.     

Polymorphisms of tumor necrosis factor-alpha are associated with increased susceptibility to gastric cancer: a meta-analysis

We conducted a meta-analysis to assess the association between tumor necrosis factor-alpha (TNF-alpha) gene TNFA-308 (G > A) and TNFA-857 (C > T) polymorphisms and gastric cancer (GC) susceptibility. We also performed subgroup analyses based on ethnicity (Caucasian, east Asian, and other populations) and tumor location [noncardia gastric cancer (NCGC)]. There were 3,335 GC patients and 5,286 controls for TNFA-308, and 1,118 GC patients and 1,591 controls for TNFA-857 in our analysis. Overall, allele contrast (A vs. G) of TNFA-308 polymorphism produced significant results in worldwide populations [Pheterogeneity = 0.05, random-effects (RE) odds ratio (OR) 1.19; 95% confidence interval (CI) 1.03-1.37, P = 0.02] and Caucasian populations (Pheterogeneity = 0.15, fixed-effects (FE), OR 1.27; 95% CI 1.11-1.45, P = 0.0005). Similar results were also obtained in recessive models and homozygote contrasts. No significant association was observed in NCGC and east Asian subgroup analysis. T variant of TNFA-857 produced significant results only in allele contrast (Pheterogeneity = 0.38, FE OR 1.17; 95% CI 1.01-1.35, P = 0.04). In conclusion, TNFA-308 locus of TNF-alpha would be a risk factor for GC, especially in Caucasian populations. Besides, TNFA-857 locus may be related to GC risk, which demonstrated changeability of results in different contrasts.     

Association between EGFR polymorphisms and the risk of lung cancer

Target: The study aimed to investigate the role of epidermal growth factor receptor (EGFR) rs6965469 and rs763317 polymorphisms in the occurrence and development of lung cancer. Methods: We used polymerase chain reaction-ligation detection reaction (PCR-LDR) method to detect the genotypes of EGFR rs6965469 and rs763317 polymorphisms and the data were analyzed by GeneMapper software. Odds ratios (ORs) with 95% confidence intervals (CIs) was calculated by χ² test to estimate the significance difference of genotype and allele frequencies in case and control groups. ORs and 95% CIs were adjusted by logistic regression analysis with age, gender, drinking and smoking. The genotypes distributions of control group were tested by Hardy-Weinberg equilibrium (HWE). Results: The genotypes frequencies of controls for rs6965469 and rs763317 polymorphims were consistent with HWE. The distribution of rs6965469 TT genotype in two groups was significantly different (P<0.05) and TT genotype was associated with an increased risk of lung cancer (OR=6.92, 95% CI=1.33-36.00). AA genotype and A allele of rs763317 were also the susceptible factors of lung cancer. Individuals with AA genotype or A allele were more likely to suffer lung cancer (AA vs. GG: OR=7.20, 95% CI=1.33-39.07; A vs. G: OR=2.61, 95% CI=1.04-6.59). Conclusions: The EGFR rs6965469 and rs763317 polymorphisms may be risk factors for lung cancer.