Adıyaman University, Adıyaman School of Health, Department of Nursing, 02040 Adıyaman, Turkey.
Gene. 2012 May 1;498(2):264-9. doi: 10.1016/j.gene.2012.02.040. Epub 2012 Feb 26.
The tumor suppressor gene Ras association domain family 1 isoform A (RASSF1A) regulates cell cycle regulation, apoptosis and microtubule stability and is inactivated by promoter hypermethylation at a high frequency in hepatocellular carcinoma (HCC). A guanine (G)/thymine (T) common single nucleotide polymorphism (SNP) at first position of codon 133 in RASSF1A gene determines an alanine (Ala) to serine (Ser) (Ala133Ser) amino acidic substitution which may alter cancer risk by influencing the function of RASSF1A protein.
To determine the association of the RASSF1A Ala133Ser polymorphism with the risk of HCC development in a Turkish population, a hospital-based case-control study was designed consisting of 236 subjects with HCC and 236 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the RASSF1A Ala133Ser polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.
Allele and genotype associations of RASSF1A Ala133Ser polymorphism with HCC susceptibility were observed in comparisons between the patient and control samples (P<0.001). Risk of HCC development in this Turkish population was significantly increased in carriers of the Ser133 variant allele of Ala133Ser polymorphism (Ala/Ser and Ser/Ser genotypes) when compared with homozygote Ala/Ala genotype (OR=5.47, 95% CI=3.63-8.25, P=0.001).
Because our results suggest for the first time that the Ser133 allele of RASSF1A Ala133Ser polymorphism may be a genetic susceptibility factor for HCC in the Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different ethnic origins.
肿瘤抑制基因 Ras 相关结构域家族 1 异构体 A（RASSF1A）调节细胞周期调控、细胞凋亡和微管稳定性，在肝细胞癌（HCC）中高频失活与启动子超甲基化有关。RASSF1A 基因密码子 133 位第一位的鸟嘌呤（G）/胸腺嘧啶（T）常见单核苷酸多态性（SNP）决定了丙氨酸（Ala）到丝氨酸（Ser）（Ala133Ser）的氨基酸取代，这可能通过影响 RASSF1A 蛋白的功能改变癌症风险。
为了确定 RASSF1A Ala133Ser 多态性与土耳其人群 HCC 发病风险的关系，进行了一项基于医院的病例对照研究，该研究包括 236 例 HCC 患者和 236 例年龄、性别、吸烟和饮酒状况相匹配的无癌症对照。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析确定 RASSF1A Ala133Ser 多态性的基因型频率。
在患者和对照样本之间的比较中，观察到 RASSF1A Ala133Ser 多态性与 HCC 易感性的等位基因和基因型关联（P<0.001）。与 Ala/Ala 纯合基因型相比，Ala133Ser 多态性的 Ser133 变体等位基因（Ala/Ser 和 Ser/Ser 基因型）携带者在土耳其人群中 HCC 发病风险显著增加（OR=5.47，95%CI=3.63-8.25，P=0.001）。
由于我们的结果首次表明，RASSF1A Ala133Ser 多态性的 Ser133 等位基因可能是土耳其人群 HCC 的遗传易感性因素，因此需要进一步的独立研究来验证我们在更大系列以及不同种族起源的患者中的发现。
