性激素结合球蛋白基因多态性与肝细胞肝癌发生的关系

Correlation between polymorphism of sex hormonebinding globulin and occurence of hepatocellular carcinoma

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0R=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DR=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。

Objective This study aims to investigate the correlation between polymorphism of sex hormone-binding globulin （SHBG） Asp327Asn （ rs6259 ） locus and oeeurence 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 nueleotide polymorphisms （SNP） of SHBG Asp327Asn were detected by ABI7500 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 Ash/Ash 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 logistic regression analysis revealed that the HCC risk of Asn/Asn ＋ Asp/Ash 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 HBV infection（ 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.