驱动蛋白家族成员1B基因rs17401966位点多态性与原发性肝细胞癌遗传易感性的关联研究

The relationship between the KIFIB （rs17401966） single nucleotide polymorphism and the genetic susceptibility to Hepatocellular carcinoma

目的分析厦门市驱动蛋白家族成员1B（KIFlB）基因rsl7401966位点多态性与原发性肝细胞癌（HCC）遗传易感性的关系。方法2011年1月至2014年10月在厦门市两家三甲医院，采用个体匹配病例一对照研究设计。病例组纳人标准：调查期间根据HCC诊断依据被首次确诊为HCC、≥18岁、现住址与调查地属同一区（县）级范围、无任何其他肿瘤史的患者；排除标准：患有其他肝脏疾病，患有HCC以外的肿瘤，患有自身免疫性肝炎或中毒性肝炎，拒绝调查或由于病危状态而无法接受调查者。对照组纳入标准：与病例组患者年龄相差不超过3岁，同性别，同期在同院接受健康普查，来自同一区（县），体检合格者；排除标准：患有肝脏疾病及既往肿瘤病史者。病例组376例，对照组403例，各采集晨起空腹静脉血5ml，进行血细胞分离及基因分型。采用x2检验和f检验比较病例组、对照组的基本情况，采用多因素logistic回归模型分析KIFIB基因rsl7401966位点多态性与HCC遗传易感性的关系。结果病例组的年龄为（61．7±12．8）岁，对照组为（60．6±12．7）岁（t=1．15，P=0．251）。病例组有肿瘤家族史比例、HBV感染阳性率分别为28．7％（108／376）、26．9％（101／376），均高于对照组[15．9％（64／403）、2．7％（11／403）]（x。分别为18．65、92．02，P值均〈0．001）。rsl7401966GA、GG基因型HCC遗传易感性分别是AA基因型的0．64（0．46～0．89）、O．54（0．32～0．92）倍，G等位基因HCC遗传易感性是A等位基因的0．76（0．60-0．96）倍。HBsAg阳性者中，rsl7401966GG基因型HCC遗传易感性是AA基因型的0．12（0．02—0．75）倍，rsl7401966G等位基因HCC遗传易感性是A等位基因的0．38（0．15～O．98）倍；HBsAg阴性者中，rsl7401966位点多态性与HCC遗传易感性相关性无统计学意义，与A等位基因相比，G等位基因HCC遗传易感性的OR（95％CI）值为0．79（0．62～1．01）。结论KIFlB基因rsl7401966GG和GA基因型、G等位基因的HCC遗传易感性较低。

Objective To study the relationship between SNP rs17401966 at the KIF1B gene and the genetic susceptibility to Hepatocellular earcinoma（HCC）.Methods All study objects were recruited from two Grade A hospitals of Amoy from January 2011 to October 2014.They were surveyed in individual matching case-control study. Accepting criterias in the cases： HCC was first diagnosed based on diagnostic basis during the investigations, over 18 years old, present addresses were as same as surveyed areas in the district （county） level range, no past history of cancers; Exclusion criterias： patients with other liver diseases. The tumor patients without HCC, patients with autoimmune hepatitis or toxic hepatitis, patients who refused to be investigated or too ill to be investigated. Accepting criterias in the controls： the control who passed the physical examination matched the case in ages （no more than 3 years old） ,sex, health screening in the same hospital over the same period and district （county）;Exclusion criterias： people with liver disease or any history of cancers. This study consisted of 376 HCC patients and 403 controls, 5 ml morning fasting venous blood of all subjects were obtained to isolate cells and distribute genotype. The differenees in general information between eases and controls were tested by X2 test and t-test. The assoeiation between SNP rs17401966 and the risk of developing HCC were assessed by using the multiple factors logistic regression. Results The mean age and standard deviation for ease and control groups were （61.7 ＋ 12.8） years and （60.6＋ 12.7） years（t=l.15,P=0.251）, respectively. The proportion of family history of caneer（28.7% （108/ 376））and the HBsAg positive rate （26.9 %（101/376）） in case group were higher than these in control group （15.9% （64/403） , 2.7% （11/403）） （X2=18.65,92.02, P〈0.001 ）. In HBsAg eaITiers, GG genotype genetic susceptibility to HCC is 0.12 （0.02-0.75）times for AA genotype, and G allele susceptibility to HCC is 0.38 （0.15-0.98） times for A allelc. In HBsAg negative group,it showed no statistical significance in the relationship between SNP rs17401966 and susceptibility to HCC, and compared with the A allele, the risk for HCC of G allele is 0.79 （0.62-1.01 ）.Conelusion The results demonstrated that the presence of the GG genotype, the GA genotype and the G allele at rs17401966 of the KIF1B gene might decrease the risk for HCC.