摘要目的 探讨性激素结合球蛋白基因Asp327Asn( rs6259)位点单核苷酸多态性与肝细胞肝癌(HCC)发生的关系.方法 以2007年1月至2010年6月广西某两家医院的621例HCC患者为病例组,以同期、同医院621例非肿瘤患者为对照,对Asp327Asn位点进行单核苷酸多态性(SNP)分型,并以多因素非条件logistic回归模型分析不同基因型人群HCC发生风险及基因型与环境因素的交互作用,采用Kaplan-Meier生存分析探讨各基因型与HCC发病年龄的关系.结果 Asp/Asp、Asp/Asn、Asn/Asn基因型在病例组中的频率分别为86.31％( 536/621)、12.40％( 77/621)、1.29％(8/621),在对照组中的分别为81.00％ (503/621)、17.39％( 108/621)、1.61％( 10/621),差异有统计学意义(x2=6.465.P＜0.05).多因素logistic回归结果表明,与携带基因型Asp/Asp个体相比,携带Asn/Asn或Asp/Asn基因型者发生HCC的风险降低(校正后OR =0.63,95％ CI:0.40～0.98).交互作用分析发现,该位点多态性与饮酒(校正后OR=3.45,95％ CI:1.74 ～6.83)、乙型肝炎病毒(HBV)感染(校正后OR=40.77,95％ CI:21.60 ～76.97)存在交互作用.生存分析显示,具有饮酒史的男性HCC患者中,携带Asp/Asp基因型者的发病年龄为(47.99±0.75)岁,比携带等位基因Asn基因型者[(53.68±2.07)岁]提前约6年(x2=6.91,P＜0.01).结论 性激素结合球蛋白基因Asp327Asn位点多态性可能与HCC发生风险和发病年龄有关.

abstractsObjective This study aims to investigate the correlation between polymorphism of sex hormone-binding globulin (SHBG) Asp327Asn (rs6259) locus and occurence of hepatocellular carcinoma (HCC).Methods 621 cases with HCC and 621 cancer-free controls from two hospitals of Guangxi were recruited from January,2007 to June,2010.Single nucleotide polymorphisms (SNP) of SHBG Asp327Asn were detected by AB17500 Fast Real-Time fluorescence quantitative PCR.Multivariate unconditional logistic regression was applied to analyze risk of HCC among different genotypes carriers and their interaction with the exposure factors.The Kaplan-Meier survival analysis was used to detect the relationship between onset age of HCC and genotypes.Results The frequencies of Asp/Asp,Asp/Asn and Asn/Aan genotype in case group were 86.31％ ( 536/621 ),12.40％ ( 77/621 ) and 1.29％ ( 8/621 ),respectively; while those in control group were 81.00％ ( 503/621 ),17.39％ ( 108/621 ) and 1.61％ ( 10/621 ),respectively,Significant difference in the genotype frequencies distribution was found between case and control groups ( x2 =6.465,P＜0.05).Compared with those harboring Asp/Asp genotype,multivariate logistie regression analysis revealed that the HCC risk of Ash/Asn + Asp/Asn genotype carriers was significantly decreased ( adjusted OR =0.63,95％ CI:0.40 -0.98 ).Interaction analysis showed that there was interaction between the polymorphisms and two exposure factors,drinking ( adjusted OR =3.45,95％ CI:1.74 - 6.83 ) and HBVinfection( adjusted OR =40.77,95％ CI:21.60 - 76.97 ).Among those male patients with history of drinking,survival analysis indicated that the mean age of onset of individuals harboring Asp/Asp genotypes ( (47.99 ±0.75 ) years-old) was 6 years earlier than those with Asn/Asn or Asp/Asn genotypes( (53.68 ±2.07) years-old) (x2 =6.91,P＜0.01).Conclusion Polymorphism of SHBG(Asp327Asn) may be associated with both the risk of HCC occurence and onset age of HCC.