Kordi Tamandani D M, Sobti R C, Shekari M
Department of Biotechnology, Panjab University, Chandigrah, India.
Clin Exp Obstet Gynecol. 2008;35(3):183-6.
Cervical cancer is the second most common cancer among women in the world, with approximately 470,000 new cases and 231,000 deaths occurring each year. Incidence is greater in developing countries such as India, where this is the most common female malignancy with almost 100,000 new cases each year. Apoptosis must be considered as a safe mechanism that controls the integrity of the cell erasing abnormal clones and it is likely that failure of apoptosis constitutes a key factor responsible for tumor formation, progression and resistance to drugs. The Fas gene plays a key role in regulation of apoptotic cell death and corruption of this signaling pathway has been shown to participate in immune escape and tumorgenesis.
A single-nucleotide polymorphism at -670 of Fas gene promoter (A/G) was examined in a total of 400 blood samples from normal healthy women and cervical cancer patients, using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique.
Significant association was observed for AG (OR = 3.0, 95% CI = (1.68-5.09, p < 0.001) and combined AG+GG (OR = 2.54, 95% CI = 1.47-4.40, p < 0.001) genotype with risk of cervical cancer. Heterozygous genotype (AG) in SCC showed a highly significant association with risk of cervical cancer (OR = 2.57, 95% CI = 1.47-4.50 p <0.001). Similarly, combined AG+GG genotype had a 2.25-fold risk for SCC patients (OR = 2.25, 95% CI = 1.30-3.90, p < 0.001). There was high increase risk of cervical cancer in passive smokers with AG and combined (AG+GG) genotypes (OR = 4.6, 95% CI = 2.07-10.32, p < 0.001 - OR = 4.9, 95% CI = 2.20-10.32, p < 0.001), respectively.
This is the first study to provide evidence for the association of a Fas -670 (A/G) gene polymorphism with the risk of cervical cancer in a North Indian population.
宫颈癌是全球女性中第二大常见癌症，每年约有47万新发病例和23.1万例死亡。在印度等发展中国家发病率更高，在印度宫颈癌是最常见的女性恶性肿瘤，每年新增病例近10万例。细胞凋亡必须被视为一种控制细胞完整性、清除异常克隆的安全机制，细胞凋亡失败很可能是肿瘤形成、进展及耐药的关键因素。Fas基因在调控凋亡性细胞死亡中起关键作用，该信号通路的破坏已被证明参与免疫逃逸和肿瘤发生。
采用聚合酶链反应和限制性片段长度多态性（PCR-RFLP）技术，对400份来自正常健康女性和宫颈癌患者的血液样本检测Fas基因启动子-670位点的单核苷酸多态性（A/G）。
观察到AG（比值比=3.0，95%置信区间=（1.68 - 5.09），p<0.001）以及AG + GG合并基因型（比值比=2.54，95%置信区间=1.47 - 4.40，p<0.001）与宫颈癌风险显著相关。在鳞状细胞癌中杂合基因型（AG）与宫颈癌风险高度显著相关（比值比=2.57，95%置信区间=1.47 - 4.50，p<0.001）。同样，AG + GG合并基因型在鳞状细胞癌患者中有2.25倍风险（比值比=2.25，95%置信区间=1.30 - 3.90，p<0.001）。携带AG和（AG + GG）合并基因型的被动吸烟者患宫颈癌风险大幅增加（分别为比值比=4.6，95%置信区间=2.07 - 10.32，p<0.001；比值比=4.9，95%置信区间=2.20 - 10.32，p<0.001）。
这是第一项为印度北部人群中Fas -670（A/G）基因多态性与宫颈癌风险之间的关联提供证据的研究。
