中华预防医学杂志
中華預防醫學雜誌
중화예방의학잡지
CHINESE JOURNAL OF
2011年
8期
711-716
,共6页
林贤东%陈刚%力超%张丽媛%师怡%周冬梅%郑雄伟
林賢東%陳剛%力超%張麗媛%師怡%週鼕梅%鄭雄偉
림현동%진강%력초%장려원%사이%주동매%정웅위
胃肿瘤%金属蛋白酶2组织抑制剂%基质金属蛋白酶-2%单核苷酸多态性%疾病遗传易感性
胃腫瘤%金屬蛋白酶2組織抑製劑%基質金屬蛋白酶-2%單覈苷痠多態性%疾病遺傳易感性
위종류%금속단백매2조직억제제%기질금속단백매-2%단핵감산다태성%질병유전역감성
Stomach neoplasms%Tissue inhibitor of metalloproteinase-2%Matrix metalloproteinase-2%Single nucleotide polymorphism%Genetic predisposition to disease
目的 探讨中国福建地区汉族人群基质金属蛋白酶2(MMP2)-1306C/T、基质金属蛋白酶2组织抑制剂(TIMP2) 2379C/T、TIMP2 303G/A单核苷酸多态性(SNP)与胃癌遗传易感性的关系.方法 本研究为病例-对照研究.选取福建地区组织学确诊的胃癌患者479例及年龄和性别等频数匹配的对照健康体检人群469名,采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)法进行MMP2-1306C/T、TIMP2 2379C/T、TIMP2 303G/A多态性检测,应用非条件logistic回归进行分析以评估不同基因型与胃癌发病风险及病理特征的关系.采用似然比检验分析MMP2和TIMP2基因之间的交互作用.结果 TIMP2 303G/A在病例组中GG、AG、AA分布的频率分别为55.9%(267/478)、38.7%(185/478)、5.4%(26/478),对照组中分别为53.1%(243/458)、36.9%(169/458)、10.0%(46/458),两者差异有统计学意义(χ2=7.0,P=0.03).携带G等位基因(GG+GA)的患者发生胃癌的风险是携带AA基因型的1.94倍(OR=1.9,95%CI:1.2～3.2).TIMP2 303A/G在肌层组中GG+AG、AA基因型分布频率分别为87.5%(70/80)、12.5%(10/80),而其在浆膜及浆膜外层组中分别为96.0%(382/398)、4.0%(16/398),两者差异有统计学意义(χ2=9.31,P=0.002);携带G等位基因(GG+AG)的患者发生肿瘤浸润的风险是携带AA基因型者的3.4倍(OR=3.4,95%CI:1.5～7.8).TIMP2 2379C/T在淋巴结无转移组中CC+CT、TT基因型分布频率分别为93.4%(113/121)、6.6%(8/121),而其在淋巴结转移组中分别为98.6%(349/354)、1.4%(5/354),两者差异有统计学意义(χ2=9.16,P=0.002);携带C等位基因(CC+CT)的患者发生淋巴结转移的风险是携带TT基因型者的4.9倍(OR=4.9,95%CI:1.6～15.3).MMP2-1306C/T的基因型分布与肿物大小、组织分化、组织浸润及淋巴结转移均未见相关性(χ2肿物大小=0.05,P=0.98;χ2浸润深度=1.87,P=0.39;χ2组织分型=0.55,P=0.76;χ2淋巴结转移=0.44,P=0.80;χ2TNM=2.6,P=0.28).MMP2-1306C/T的SNP与TIMP2 303A/G、TIMP2 2379C/T间无明显的交互作用(χ2值分别为0.98、0.80,P值分别为0.81、0.85).结论 TIMP2基因多态性与胃癌的发生及侵袭转移密切相关,有可能成为胃癌预后的新分子指标.
目的 探討中國福建地區漢族人群基質金屬蛋白酶2(MMP2)-1306C/T、基質金屬蛋白酶2組織抑製劑(TIMP2) 2379C/T、TIMP2 303G/A單覈苷痠多態性(SNP)與胃癌遺傳易感性的關繫.方法 本研究為病例-對照研究.選取福建地區組織學確診的胃癌患者479例及年齡和性彆等頻數匹配的對照健康體檢人群469名,採用基質輔助激光解吸電離飛行時間質譜(MALDI-TOF-MS)法進行MMP2-1306C/T、TIMP2 2379C/T、TIMP2 303G/A多態性檢測,應用非條件logistic迴歸進行分析以評估不同基因型與胃癌髮病風險及病理特徵的關繫.採用似然比檢驗分析MMP2和TIMP2基因之間的交互作用.結果 TIMP2 303G/A在病例組中GG、AG、AA分佈的頻率分彆為55.9%(267/478)、38.7%(185/478)、5.4%(26/478),對照組中分彆為53.1%(243/458)、36.9%(169/458)、10.0%(46/458),兩者差異有統計學意義(χ2=7.0,P=0.03).攜帶G等位基因(GG+GA)的患者髮生胃癌的風險是攜帶AA基因型的1.94倍(OR=1.9,95%CI:1.2～3.2).TIMP2 303A/G在肌層組中GG+AG、AA基因型分佈頻率分彆為87.5%(70/80)、12.5%(10/80),而其在漿膜及漿膜外層組中分彆為96.0%(382/398)、4.0%(16/398),兩者差異有統計學意義(χ2=9.31,P=0.002);攜帶G等位基因(GG+AG)的患者髮生腫瘤浸潤的風險是攜帶AA基因型者的3.4倍(OR=3.4,95%CI:1.5～7.8).TIMP2 2379C/T在淋巴結無轉移組中CC+CT、TT基因型分佈頻率分彆為93.4%(113/121)、6.6%(8/121),而其在淋巴結轉移組中分彆為98.6%(349/354)、1.4%(5/354),兩者差異有統計學意義(χ2=9.16,P=0.002);攜帶C等位基因(CC+CT)的患者髮生淋巴結轉移的風險是攜帶TT基因型者的4.9倍(OR=4.9,95%CI:1.6～15.3).MMP2-1306C/T的基因型分佈與腫物大小、組織分化、組織浸潤及淋巴結轉移均未見相關性(χ2腫物大小=0.05,P=0.98;χ2浸潤深度=1.87,P=0.39;χ2組織分型=0.55,P=0.76;χ2淋巴結轉移=0.44,P=0.80;χ2TNM=2.6,P=0.28).MMP2-1306C/T的SNP與TIMP2 303A/G、TIMP2 2379C/T間無明顯的交互作用(χ2值分彆為0.98、0.80,P值分彆為0.81、0.85).結論 TIMP2基因多態性與胃癌的髮生及侵襲轉移密切相關,有可能成為胃癌預後的新分子指標.
목적 탐토중국복건지구한족인군기질금속단백매2(MMP2)-1306C/T、기질금속단백매2조직억제제(TIMP2) 2379C/T、TIMP2 303G/A단핵감산다태성(SNP)여위암유전역감성적관계.방법 본연구위병례-대조연구.선취복건지구조직학학진적위암환자479례급년령화성별등빈수필배적대조건강체검인군469명,채용기질보조격광해흡전리비행시간질보(MALDI-TOF-MS)법진행MMP2-1306C/T、TIMP2 2379C/T、TIMP2 303G/A다태성검측,응용비조건logistic회귀진행분석이평고불동기인형여위암발병풍험급병리특정적관계.채용사연비검험분석MMP2화TIMP2기인지간적교호작용.결과 TIMP2 303G/A재병례조중GG、AG、AA분포적빈솔분별위55.9%(267/478)、38.7%(185/478)、5.4%(26/478),대조조중분별위53.1%(243/458)、36.9%(169/458)、10.0%(46/458),량자차이유통계학의의(χ2=7.0,P=0.03).휴대G등위기인(GG+GA)적환자발생위암적풍험시휴대AA기인형적1.94배(OR=1.9,95%CI:1.2～3.2).TIMP2 303A/G재기층조중GG+AG、AA기인형분포빈솔분별위87.5%(70/80)、12.5%(10/80),이기재장막급장막외층조중분별위96.0%(382/398)、4.0%(16/398),량자차이유통계학의의(χ2=9.31,P=0.002);휴대G등위기인(GG+AG)적환자발생종류침윤적풍험시휴대AA기인형자적3.4배(OR=3.4,95%CI:1.5～7.8).TIMP2 2379C/T재림파결무전이조중CC+CT、TT기인형분포빈솔분별위93.4%(113/121)、6.6%(8/121),이기재림파결전이조중분별위98.6%(349/354)、1.4%(5/354),량자차이유통계학의의(χ2=9.16,P=0.002);휴대C등위기인(CC+CT)적환자발생림파결전이적풍험시휴대TT기인형자적4.9배(OR=4.9,95%CI:1.6～15.3).MMP2-1306C/T적기인형분포여종물대소、조직분화、조직침윤급림파결전이균미견상관성(χ2종물대소=0.05,P=0.98;χ2침윤심도=1.87,P=0.39;χ2조직분형=0.55,P=0.76;χ2림파결전이=0.44,P=0.80;χ2TNM=2.6,P=0.28).MMP2-1306C/T적SNP여TIMP2 303A/G、TIMP2 2379C/T간무명현적교호작용(χ2치분별위0.98、0.80,P치분별위0.81、0.85).결론 TIMP2기인다태성여위암적발생급침습전이밀절상관,유가능성위위암예후적신분자지표.
Objective This study was to explore the correlations between genetic variants in MMP2-1306C/T,TIMP2 2379C/T,TIMP2 303G/A and the genetic susceptibility to gastric carcinoma(GC) in Fujian province,China.Methods A case-control study was conducted.Polymorphisms of MMP2-1306C/T,TIMP2 2379C/T,TIMP2 303G/A in 479 gastric carcinoma patients and 469 cancer-free controls,frequency-matched by age and sex,were determined by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry(MALDI-TOF-MS).Multivariate logistic regression analysis was used to evaluate the correlations between the polymorphisms with the susceptibility to gastric cancer.Tests for an interaction between the MMP2-1306C/T and TIMP2 2379C/T or TIMP2 303G/A were performed using the likelihood ratio test.Results The frequencies of GG,AG,AA of TIMP2 303G/A in gastric cancer group were 55.9%(267/478),38.7%(185/478) and 5.4%(26/478); and those in control group were 53.1%(243/458),36.9%(169/458) and 10.0%(46/458),which showed a significant difference between the patient and control groups (χ2=7.0,P=0.03).As compared with AA genotype,patients with GG+AG had a significantly higher risk of the cancer with OR of 1.94 (95%CI:1.2-3.2).The frequencies of GG+AG and AA of TIMP2 303G/A in the muscle group were 87.5%(70/80),12.5%(10/80),however,those in the serosa and beyond group were 96.0%(382/398),4.0%(16/398),respectively,which showed a significant difference between the patient in muscle group and the serosa and beyond group(χ2=9.32,P=0.002).As compared with AA genotype,patients with GG+AG had a significantly higher risk in tumor invasion with OR of 3.4(95%CI:1.5-7.8).The frequencies of CC+CT,TT of TIMP2 2379C/T in the lymphoma node non-metastasis group were 93.4% (113/121),and 6.6%(8/121),but those in the lymphoma node metastasis group were 98.6% (349/354) and 1.4%(5/354),respectively,which showed a significant difference between the patient in the lymphoma node non-metastasis group and in the lymphoma node metastasis group in genotype distributions of TIMP2 2379C/T(χ2=9.16,P=0.002).As compared with TT genotype,patients with CC+CT had a significantly higher risk in lymph node metastasis with OR of 4.9 (95%CI:1.6-15.3).MMP2-1306C/T genotype was not associated with tumor size,tissue differentiation,invasion,TNM nor lymph node metastasis of gastric carcinoma (χ2tumor size=0.05,P=0.98; χ2depth of invasion=1.87,P=0.39; χ2histological type=0.55,P=0.76;χ2LN metastasis=0.44,P=0.80; χ2TNM=2.6,P=0.28).There was no significant interaction between the polymorphisms of the two genes observed (χ2 values were 0.98 and 0.80,P values were 0.81 and 0.85).Conclusion Polymorphism of TIMP2 is significantly related with occurrence and development of GC and maybe acts as a new biomarker of GC in prognosis.
