基质金属蛋白酶-1(-1607)1G/2G基因多态性与鼻咽癌相关性研究

MMP-1(-1607)1G/2G gene polymorphism and susceptibility to nasopharyngeal carcinoma in Han population in Yunnan China

目的研究基质金属蛋白酶-1(matri xmetalloproteinases-1,MMP-1)(-1607)1G/2G基因单核苷酸多态性与云南汉族鼻咽癌发病风险、各临床参数及预后相关性。方法按病例对照研究,利用聚合酶链反应-限制性片段长度多态性(restriction fragment lengthpolymorphism-PCR,RFLP-PCR),对241例云南籍汉族鼻咽癌患者和272例云南籍汉族健康对照进行基因分型,分析基因型与云南汉族鼻咽癌发病风险及预后关系。结果分别携带1G2G、2G2G基因型个体罹患鼻咽癌风险性是携带1G1G基因型者3.10倍和9.93倍;2G等位基因与T分期、颈淋巴结转移、临床分期明显相关(P<0.05)。吸烟与MMP-1(-1607)2G等位基因存在相加交互作用;MMP-12G等位基因与患者预后不良相关,且2G2G基因型为独立预后影响因素。结论MMP-1(-1607)1G/2G多态性是云南汉族鼻咽癌遗传易感因素,与吸烟暴露呈现交互作用,同时与鼻咽癌预后相关。

OBJECTIVE The aim of this study was to investigate the susceptibility and prognostic implications of the MMP-1（-1607）1G/2G polymorphism to NPC in Han population in Yunnan China.METHODS Two hundred and forty one cases with NPC and 272 matched cancer-free controls were genotyped for the MMP-1（-1607）1G/2G polymorphism by polymerase chain reaction-restriction fragment length polymorphism（PCRRFLP）.RESULTS The MMP-1（-1607）2G allele showed a significant influence on the susceptibility to NPC（OR =4.35,95%CI 2.66～7.10,P0.001）.By using the 1G1G genotype as reference,a significant association was found between the 2G2G genotype（OR =9.93,95%CI 5.38～18.32,P0.001） and 1G2G（OR =3.10,95%CI 1.85～5.19,P0.001）.The MMP-1（-1607） 2G allele was associated with the risk of developing NPC.An association was ascertained with MMP-1（-1607） 2G allele among large tumor size（T3,T4）,lymph node metastasis and advanced stages（Ⅲ,IV）（P 0.05）.Furthermore,smoking may increase the risk of developing NPC interacting with MMP-1（-1607） 1G/2G polymorphisms.The MMP-1（-1607）2G allele showed a significant association with reduced 5-year survival rate of subjects.Especially,MMP-1（-1607） 2G2G genotype was independent prognostic factor in NPC（RR=3.10,P0.001）.CONCLUSION The MMP-1（-1607）2G allele may represent a marker for the increased risk and poor prognosis of nasopharyngeal carcinoma.