中华预防医学杂志
中華預防醫學雜誌
중화예방의학잡지
CHINESE JOURNAL OF
2012年
1期
53-57
,共5页
鲍倩%何帮顺%陈丽萍%顾玲%聂珍琳%王书奎
鮑倩%何幫順%陳麗萍%顧玲%聶珍琳%王書奎
포천%하방순%진려평%고령%섭진림%왕서규
结直肠肿瘤%多态性,单核苷酸%DNA(胞嘧啶-5-)—甲基转移酶
結直腸腫瘤%多態性,單覈苷痠%DNA(胞嘧啶-5-)—甲基轉移酶
결직장종류%다태성,단핵감산%DNA(포밀정-5-)—갑기전이매
Colorectal neoplasms%Polymorphism,single nucleotide%DNA (cytosine-5-) methyltransferase
目的 探讨DNA甲基转移酶3B(DNMT3B)基因启动子区- 149C→T( rs2424913)和- 579 G→T (rs1569686)单核苷酸多态性与江苏汉族人群结直肠癌易感性的关系.方法 以江苏省南京市某医院于2009年1月至2010年7月确诊的544例结直肠癌患者作为病例组(包括结肠癌患者280例,直肠癌患者264例),以533名健康体检人员作为对照组.提取研究对象外周血基因组DNA,采用PCR-限制性片段长度多态性(PCR-RFLP)方法检测DNMT3B基因启动子区- 149C→T和- 579G→T单核苷酸多态性.结果 DNMT3B基因- 149C→T多态性在病例组[TT:98.90％( 538/544)；CT:1.10％( 6/544)]与对照组[TT:97.75％ (521/533)；CT:2.25％( 12/533)]中分布的差异无统计学意义(x2 =2.07,P=0.150)；在病例组与对照组中均未检测出CC基因型.DNMT3B基因- 149位点CT基因型与结直肠癌发病无相关性(校正后OR=0.48,95％CI:0.18 ～ 1.30).DNMT3B基因- 579G→T多态性在病例组[TT:90.07％ (490/544)；GT:9.19％ (50/544)；GG:0.74％ (4/544)]与对照组[TT:81.80％ (436/533)；GT:17.82％ (95/533)；GG:0.38％ (2/533)]中基因型分布的差异有统计学意义(x2=15.49,P＜0.05)；与TT基因型相比,携带GG和GT基因型可降低结直肠癌的患病风险(校正OR =0.50,95％CI:0.35 ～0.72).分层分析显示,结肠癌患者DNMT3B基因- 579G→T多态性[TT:92.50％ (259/280)；GT:7.50％ (21/280)]与对照组[TT:81.80％ (436/533)；GT:17.82％(95/533)；GG:0.38％(2/533)]相比,基因型分布差异有统计学意义(x2=13.53,P＜0.05),在结肠癌患者中未检测到GG基因型；直肠癌患者基因型分布[TT:87.50％ (231/264)；GT:10.98％(29/264)；GG:1.52％ (4/264)]与对照组[TT:81.80％(436/533)；GT:17.82％ (95/533)；GG:0.38％(2/533)]比较,差异有统计学意义(x2 =5.64,P=0.018).与TT基因型相比,携带- 579位点GG和GT基因型可降低结肠癌和直肠癌的发病风险(结肠癌:校正OR=0.38,95％ CI:0.23 ～0.63；直肠癌:校正OR=0.65,95％ CI:0.42 ～0.99).而结肠癌患者DNMT3B基因- 149C→T多态性基因型分布[TT:98.57％( 276/280)；CT: 1.43％( 4/280)]与对照组[TT:97.75％( 521/533)；CT:2.25％(12/533)]比较,差异无统计学意义(x2=0.82,P=0.366);直肠癌患者基因型分布[TTT:99.24％(262/264)；CT:0.76％ (2/264)]与对照组[TT:97.75％ (521/533)；CT:2.25％(12/533)]比较,差异也无统计学意义(x2=1.89,P=0.169).结论 在中国人群中,DNMT3B基因- 579位点G等位基因在结直肠癌发生过程中是一个潜在的保护因素,而- 149位点的基因多态性与结直肠癌的发生和发展无相关性.
目的 探討DNA甲基轉移酶3B(DNMT3B)基因啟動子區- 149C→T( rs2424913)和- 579 G→T (rs1569686)單覈苷痠多態性與江囌漢族人群結直腸癌易感性的關繫.方法 以江囌省南京市某醫院于2009年1月至2010年7月確診的544例結直腸癌患者作為病例組(包括結腸癌患者280例,直腸癌患者264例),以533名健康體檢人員作為對照組.提取研究對象外週血基因組DNA,採用PCR-限製性片段長度多態性(PCR-RFLP)方法檢測DNMT3B基因啟動子區- 149C→T和- 579G→T單覈苷痠多態性.結果 DNMT3B基因- 149C→T多態性在病例組[TT:98.90％( 538/544)；CT:1.10％( 6/544)]與對照組[TT:97.75％ (521/533)；CT:2.25％( 12/533)]中分佈的差異無統計學意義(x2 =2.07,P=0.150)；在病例組與對照組中均未檢測齣CC基因型.DNMT3B基因- 149位點CT基因型與結直腸癌髮病無相關性(校正後OR=0.48,95％CI:0.18 ～ 1.30).DNMT3B基因- 579G→T多態性在病例組[TT:90.07％ (490/544)；GT:9.19％ (50/544)；GG:0.74％ (4/544)]與對照組[TT:81.80％ (436/533)；GT:17.82％ (95/533)；GG:0.38％ (2/533)]中基因型分佈的差異有統計學意義(x2=15.49,P＜0.05)；與TT基因型相比,攜帶GG和GT基因型可降低結直腸癌的患病風險(校正OR =0.50,95％CI:0.35 ～0.72).分層分析顯示,結腸癌患者DNMT3B基因- 579G→T多態性[TT:92.50％ (259/280)；GT:7.50％ (21/280)]與對照組[TT:81.80％ (436/533)；GT:17.82％(95/533)；GG:0.38％(2/533)]相比,基因型分佈差異有統計學意義(x2=13.53,P＜0.05),在結腸癌患者中未檢測到GG基因型；直腸癌患者基因型分佈[TT:87.50％ (231/264)；GT:10.98％(29/264)；GG:1.52％ (4/264)]與對照組[TT:81.80％(436/533)；GT:17.82％ (95/533)；GG:0.38％(2/533)]比較,差異有統計學意義(x2 =5.64,P=0.018).與TT基因型相比,攜帶- 579位點GG和GT基因型可降低結腸癌和直腸癌的髮病風險(結腸癌:校正OR=0.38,95％ CI:0.23 ～0.63；直腸癌:校正OR=0.65,95％ CI:0.42 ～0.99).而結腸癌患者DNMT3B基因- 149C→T多態性基因型分佈[TT:98.57％( 276/280)；CT: 1.43％( 4/280)]與對照組[TT:97.75％( 521/533)；CT:2.25％(12/533)]比較,差異無統計學意義(x2=0.82,P=0.366);直腸癌患者基因型分佈[TTT:99.24％(262/264)；CT:0.76％ (2/264)]與對照組[TT:97.75％ (521/533)；CT:2.25％(12/533)]比較,差異也無統計學意義(x2=1.89,P=0.169).結論 在中國人群中,DNMT3B基因- 579位點G等位基因在結直腸癌髮生過程中是一箇潛在的保護因素,而- 149位點的基因多態性與結直腸癌的髮生和髮展無相關性.
목적 탐토DNA갑기전이매3B(DNMT3B)기인계동자구- 149C→T( rs2424913)화- 579 G→T (rs1569686)단핵감산다태성여강소한족인군결직장암역감성적관계.방법 이강소성남경시모의원우2009년1월지2010년7월학진적544례결직장암환자작위병례조(포괄결장암환자280례,직장암환자264례),이533명건강체검인원작위대조조.제취연구대상외주혈기인조DNA,채용PCR-한제성편단장도다태성(PCR-RFLP)방법검측DNMT3B기인계동자구- 149C→T화- 579G→T단핵감산다태성.결과 DNMT3B기인- 149C→T다태성재병례조[TT:98.90％( 538/544)；CT:1.10％( 6/544)]여대조조[TT:97.75％ (521/533)；CT:2.25％( 12/533)]중분포적차이무통계학의의(x2 =2.07,P=0.150)；재병례조여대조조중균미검측출CC기인형.DNMT3B기인- 149위점CT기인형여결직장암발병무상관성(교정후OR=0.48,95％CI:0.18 ～ 1.30).DNMT3B기인- 579G→T다태성재병례조[TT:90.07％ (490/544)；GT:9.19％ (50/544)；GG:0.74％ (4/544)]여대조조[TT:81.80％ (436/533)；GT:17.82％ (95/533)；GG:0.38％ (2/533)]중기인형분포적차이유통계학의의(x2=15.49,P＜0.05)；여TT기인형상비,휴대GG화GT기인형가강저결직장암적환병풍험(교정OR =0.50,95％CI:0.35 ～0.72).분층분석현시,결장암환자DNMT3B기인- 579G→T다태성[TT:92.50％ (259/280)；GT:7.50％ (21/280)]여대조조[TT:81.80％ (436/533)；GT:17.82％(95/533)；GG:0.38％(2/533)]상비,기인형분포차이유통계학의의(x2=13.53,P＜0.05),재결장암환자중미검측도GG기인형；직장암환자기인형분포[TT:87.50％ (231/264)；GT:10.98％(29/264)；GG:1.52％ (4/264)]여대조조[TT:81.80％(436/533)；GT:17.82％ (95/533)；GG:0.38％(2/533)]비교,차이유통계학의의(x2 =5.64,P=0.018).여TT기인형상비,휴대- 579위점GG화GT기인형가강저결장암화직장암적발병풍험(결장암:교정OR=0.38,95％ CI:0.23 ～0.63；직장암:교정OR=0.65,95％ CI:0.42 ～0.99).이결장암환자DNMT3B기인- 149C→T다태성기인형분포[TT:98.57％( 276/280)；CT: 1.43％( 4/280)]여대조조[TT:97.75％( 521/533)；CT:2.25％(12/533)]비교,차이무통계학의의(x2=0.82,P=0.366);직장암환자기인형분포[TTT:99.24％(262/264)；CT:0.76％ (2/264)]여대조조[TT:97.75％ (521/533)；CT:2.25％(12/533)]비교,차이야무통계학의의(x2=1.89,P=0.169).결론 재중국인군중,DNMT3B기인- 579위점G등위기인재결직장암발생과정중시일개잠재적보호인소,이- 149위점적기인다태성여결직장암적발생화발전무상관성.
Objective To explore the correlation between the polymorphism in the DNA methyltransferase-3B( DNMT3B ) gene promoter single nucleotide polymorphism ( SNP ) - 149C → T (rs2424913) and- 579G→T (rs1569686)and the genetic susceptibility to colorectal cancer in Jiangsu population.Methods Genomic DNA was extracted from the leukocyte cell of blood samples collected from 544 colorectal cancer(CRC) patients (including 280 cases of colon cancer and 264 cases of rectal cancer)since January 2009 and July 2010,in a hospital,Jiangsu Province.The same samples were collected from the other 533 control subjects.Polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing analysis were employed to assess the polymorphism of DNMT3B gene promoter - 149C→T and - 579G→T.Results For DNMT3B - 149C→T,no significant deviation was observed in the genotype distributions of polymorphisms between CRC cases (TT: 98.90％ (538/544);CT: 1.10％ (6/544)) and controls (TT: 97.75％ (521/533) ; CT: 2.25％ (12/533) ) (x2 =2.07,P =0.15).The CC genotype was not detected in either patients or control subjects.The DNMT3B -149CT genotype was not associated with the risk of CRC ( adjusted OR =0.48,95 ％ CI:0.18 - 1.30).For DNMT3B - 579G→T,the genotype distributions of polymorphisms in CRC patients ( TT: 90.07％ (490/544) ; GT:9.19％ (50/544); GG: 0.74％ (4/544)) were significantly different from those in control group (TT:81.80％ (436/533) ; GT: 17.82％ (95/533) ; GG: 0.38％ (2/533) ) (x2 =15.49,P ＜ 0.05 ).The results showed that the -579 G allele could significantly decrease the risk of CRC (adjusted OR =0.50,95％ CI:0.35 - 0.72) in comparison with the - 579 TT genotype.In addition,stratification analysis showed that for DNMT3B- 579G→T,the genotype distributions of polymor-phisms in colon cancer (TT: 92.50％(259/280); GT: 7.50％ (21/280)) were significantly different from those in the controls (TT: 81.80％(436/533) ; GT: 17.82％ (95/533) ; GG: 0.38％ (2/533)) ( x2 =13.53,P ＜0.05) ; and similar result was found in rectal cancer (TT: 87.50％ (231/264) ; GT: 10.98％ (29/264) ; GG: 1.52％ (4/264)) and controls (TT: 81.80％ (436/533); GT: 17.82％ (95/533); GG: 0.38％ (2/533)) (x2=5.64,P=0.018).G allele carriers could decrease the risk of colon cancer ( adjusted OR =0.38,95％ CI: 0.23 -0.63 ),and the risk of rectal cancer ( adjusted OR =0.65,95％ CI: 0.42 - 0.99 ).However,for DNMT3B -149C→T,there were no significant deviation in the genotype distributions of polymorphisms between colon cancer ( TT: 98.57％ (276/280) ; CT: 1.43 ％ ( 4/280 ) ) and controls ( TT: 97.75 ％ ( 521/533 ) ; CT:2.25％ (12/533)) (x2 =0.82,P =0.366); and there was no significant deviation between rectal cancer (TT: 99.24％ (262/264); CT: 0.76％ (2/264)) and controls (TT: 97.75％ (521/533); CT: 2.25％(12/533) ) either ( x2 =1.89,P =0.169 ).Conclusion Our research demonstrates that the - 579 G allele is a potential protective factor for the occurrence of CRC,however,the polymorphism of DNMT3B - 149 gene shows no close correlation with the occurrence and development of CRC among Chinese population.
