中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
CHINESE JOURNAL OF ONCOLOGY
2012年
5期
341-347
,共7页
孙刚%王江涛%马斌林%耿中利%任光辉%单美慧%马斌%马莉莉%王岩
孫剛%王江濤%馬斌林%耿中利%任光輝%單美慧%馬斌%馬莉莉%王巖
손강%왕강도%마빈림%경중리%임광휘%단미혜%마빈%마리리%왕암
乳腺肿瘤%BARD1基因%单核苷酸多态性%遗传易感性%维吾尔族
乳腺腫瘤%BARD1基因%單覈苷痠多態性%遺傳易感性%維吾爾族
유선종류%BARD1기인%단핵감산다태성%유전역감성%유오이족
Breast neoplasms%BARD1 gene%Single nucleotide polymorphism%Genetic susceptibility%Uygur nationality
目的 探讨BARD1基因Pro24Ser(C/T)、Arg378Ser(G/C)和Val507Met( G/A)单核苷酸多态性(SNPa)与新疆维吾尔族妇女早发性乳腺癌易感性的关系.方法 采用病例-对照研究,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测新疆地区144例维吾尔族妇女早发性乳腺癌(年龄≤40岁)和136例维吾尔族健康女性BARD1基因Pr024Ser (C/T)、Arg378 Ser( G/C)和Val507Met (G/A)位点基因型,比较各位点基因型分布与维吾尔族妇女早发性乳腺癌发病风险的关系.结果 初潮年龄早、初产年龄晚和肿瘤家族史可能是新疆地区维吾尔族早发性乳腺癌患者发病的高危因素.在维吾尔族早发性乳腺癌组和健康对照组中,BARD1基因Pro24Ser (C/T)、Arg378Ser(G/C)和Val507Met( G/A)位点的各基因型频率差异有统计学意义(P＜0.05).Logistic同归分析表明,Pro24Ser(C/T)位点TT(OR =0.117,95％ CI为0.058～0.236)及显性模型CT+ TT( OR=0.279,95％CI为0.157～0.494)、Arg378Ser( G/C)位点CC(OR=0.348,95％CI为0.145～0.834)和Val507 Met( G/A)位点AA(OR=0.359,95％ CI为0.167～0.774)的改变,可以显著降低维吾尔族早发性乳腺癌发病风险,并且各位点之间存在协同作用；同时,显性模型CT+TT、GC +CC、GA +AA间的交互作用可以降低52.1％的乳腺癌发病风险(OR=0.479,95％ CI为0.230～0.995).分层分析结果显示,Pro24Ser(C/T)和Arg378Ser( G/C)位点基因突变型的保护作用在初潮年龄早和肿瘤家族史阴性患者中更为明显.随着患者初潮年龄的增加,这种保护作用逐渐降低.结论 BARD1基因Pr24Ser(C/T)、Arg378Ser(G/C)和Val507Met( G/A)位点的SNPs变化,能够显著降低新疆地区维吾尔族妇女早发性乳腺癌的发病风险,初潮年龄早和无肿瘤家族史可以增加突变等位基因的保护作用.
目的 探討BARD1基因Pro24Ser(C/T)、Arg378Ser(G/C)和Val507Met( G/A)單覈苷痠多態性(SNPa)與新疆維吾爾族婦女早髮性乳腺癌易感性的關繫.方法 採用病例-對照研究,應用聚閤酶鏈反應-限製性片段長度多態性(PCR-RFLP)方法檢測新疆地區144例維吾爾族婦女早髮性乳腺癌(年齡≤40歲)和136例維吾爾族健康女性BARD1基因Pr024Ser (C/T)、Arg378 Ser( G/C)和Val507Met (G/A)位點基因型,比較各位點基因型分佈與維吾爾族婦女早髮性乳腺癌髮病風險的關繫.結果 初潮年齡早、初產年齡晚和腫瘤傢族史可能是新疆地區維吾爾族早髮性乳腺癌患者髮病的高危因素.在維吾爾族早髮性乳腺癌組和健康對照組中,BARD1基因Pro24Ser (C/T)、Arg378Ser(G/C)和Val507Met( G/A)位點的各基因型頻率差異有統計學意義(P＜0.05).Logistic同歸分析錶明,Pro24Ser(C/T)位點TT(OR =0.117,95％ CI為0.058～0.236)及顯性模型CT+ TT( OR=0.279,95％CI為0.157～0.494)、Arg378Ser( G/C)位點CC(OR=0.348,95％CI為0.145～0.834)和Val507 Met( G/A)位點AA(OR=0.359,95％ CI為0.167～0.774)的改變,可以顯著降低維吾爾族早髮性乳腺癌髮病風險,併且各位點之間存在協同作用；同時,顯性模型CT+TT、GC +CC、GA +AA間的交互作用可以降低52.1％的乳腺癌髮病風險(OR=0.479,95％ CI為0.230～0.995).分層分析結果顯示,Pro24Ser(C/T)和Arg378Ser( G/C)位點基因突變型的保護作用在初潮年齡早和腫瘤傢族史陰性患者中更為明顯.隨著患者初潮年齡的增加,這種保護作用逐漸降低.結論 BARD1基因Pr24Ser(C/T)、Arg378Ser(G/C)和Val507Met( G/A)位點的SNPs變化,能夠顯著降低新疆地區維吾爾族婦女早髮性乳腺癌的髮病風險,初潮年齡早和無腫瘤傢族史可以增加突變等位基因的保護作用.
목적 탐토BARD1기인Pro24Ser(C/T)、Arg378Ser(G/C)화Val507Met( G/A)단핵감산다태성(SNPa)여신강유오이족부녀조발성유선암역감성적관계.방법 채용병례-대조연구,응용취합매련반응-한제성편단장도다태성(PCR-RFLP)방법검측신강지구144례유오이족부녀조발성유선암(년령≤40세)화136례유오이족건강녀성BARD1기인Pr024Ser (C/T)、Arg378 Ser( G/C)화Val507Met (G/A)위점기인형,비교각위점기인형분포여유오이족부녀조발성유선암발병풍험적관계.결과 초조년령조、초산년령만화종류가족사가능시신강지구유오이족조발성유선암환자발병적고위인소.재유오이족조발성유선암조화건강대조조중,BARD1기인Pro24Ser (C/T)、Arg378Ser(G/C)화Val507Met( G/A)위점적각기인형빈솔차이유통계학의의(P＜0.05).Logistic동귀분석표명,Pro24Ser(C/T)위점TT(OR =0.117,95％ CI위0.058～0.236)급현성모형CT+ TT( OR=0.279,95％CI위0.157～0.494)、Arg378Ser( G/C)위점CC(OR=0.348,95％CI위0.145～0.834)화Val507 Met( G/A)위점AA(OR=0.359,95％ CI위0.167～0.774)적개변,가이현저강저유오이족조발성유선암발병풍험,병차각위점지간존재협동작용；동시,현성모형CT+TT、GC +CC、GA +AA간적교호작용가이강저52.1％적유선암발병풍험(OR=0.479,95％ CI위0.230～0.995).분층분석결과현시,Pro24Ser(C/T)화Arg378Ser( G/C)위점기인돌변형적보호작용재초조년령조화종류가족사음성환자중경위명현.수착환자초조년령적증가,저충보호작용축점강저.결론 BARD1기인Pr24Ser(C/T)、Arg378Ser(G/C)화Val507Met( G/A)위점적SNPs변화,능구현저강저신강지구유오이족부녀조발성유선암적발병풍험,초조년령조화무종류가족사가이증가돌변등위기인적보호작용.
Objective To investigate the association between single nucleotide polymorphisms (SNPs) of BARD1 gene and susceptibility of early-onset breast cancer in Uygur women in Xinjiang.Methods A case-control study was designed to explore the genotypes of Pro24Ser (C/T),Arg378Ser ( G/C) and Val507Met (G/A) of BARD1 gene,detected by PCR-restriction fragment length polymorphism (PCR-RFLP) assay,in 144 early-onset breast cancer cases of Uygur women ( ≤40 years) and 136 cancerfree controls matched by age and ethnicity.The association between SNPs of BARD1 gene and risk of early-onset breast cancer in Uygur women was analyzed by unconditional logistic regression model.Results Early age at menarche,late age at first pregnancy,and positive family history of cancer may be important risk factors of early-onset breast cancer in Uygur women in Xinjiang.The frequencies of genotypes of Pro24Ser (C/T),Arg378Ser (G/C) and Val507Met (G/A) of BARD1 gene showed significant differences between the cancer cases and cancer-free controls ( P ＜ 0.05 ).Compared with wild-type genotype Pro24Ser CC,it showed a lower incidence of early-onset breast cancer in Uygur women with variant genotypes of Pro24Ser TT ( OR =0.117,95％ CI =0.058-0.236),and dominance-genotype CT + TT ( OR =0.279,95％ CI =0.157-0.494),or Arg378Ser CC (OR =0.348,95％ CI=0.145-0.834) and Val507Met AA(OR =0.359,95％ CI =0.167-0.774).Furthermore,SNPS in three polymorphisms would have synergistic effects on the risk of breast cancer.In addition,the SNP-SNP interactions of dominance-genotypes( CT + TT,GC + CC and GA + AA ) showed a 52.1％ lower incidence of early-onset breast cancer in Uygur women ( OR =0.479,95 ％ CI =0.230-0.995 ).Stratified analysis indicated that the protective effect of carrying T variant genotype (CT/TT) in Pro24Ser and carrying C variant genotype (GC/CC) in Arg378Ser were more evident in subjects with early age at menarche and negative family history of cancer.With an older menarche age,the protective effect was weaker.Conclusions SNPs of Pro24Ser(C/T),Arg378Ser (G/C) and Val507Met (G/A) of BARD1 gene are associated with significantly decreased risk of early-onset breast cancer in Uygur women in Xinjiang.Early age at menarche and negative family history of cancer can enhance the protective effect of mutant allele.
