PTEN polymorphisms and the risk of esophageal carcinoma and gastric cardiac carcinoma in a high incidence region of China
PTEN polymorphisms and the risk of esophageal carcinoma and gastric cardiac carcinoma in a high incidence region of China
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DOI：
10.1111/j.1442-2050.2007.00786.x
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发表时间：
2008-01-01
影响因子：
2.6
通讯作者：
Zhang, J. H.
中科院分区：
文献类型：
--
作者：
Ge, H.;Cao, Y. Y.;Zhang, J. H.
PTEN作为一种肿瘤抑制基因，在调节细胞生长、增殖和凋亡方面发挥着重要作用。两个常见的基因多态-9C/G和IVS4(-/+)可能改变疾病的易感性。为验证PTEN基因变异在食管鳞癌和胃腺癌发病机制中的作用，对河北省食管鳞癌高发区的350例食管鳞癌、257例贲门腺癌和634例健康对照进行了病例对照研究。采用聚合酶链式反应-限制性片段长度多态性分析(PCR-RFLP)对PTEN基因多态性进行分型。结果表明，上消化道肿瘤家族史(UGIC)显著增加食管鳞癌和GCA的发病风险(调整年龄、性别和吸烟状况的OR分别为1.73和1.67；95%CI分别为1.29~2.32和1.28~2.19)。PTEN-9C/G基因在癌症患者和对照组中的总体分布无显著差异。与PTEN IVS4-/-型相比，IVS4+/+型显著降低ESCC和GCA的发病风险，其校正OR分别为0.64(95%CI=0.44~0.94)和0.63(95%CI=0.41~0.98)。按性别、年龄、吸烟状况和UGIC家族史分层分析显示，PTEN IVS4-/+基因型仅在有UGIC家族史的人群中降低ESCC的风险(校正OR=0.55，95%CI=0.34~0.90)。IVS4+/+基因型降低男性ESCC和GCA的易感性(校正OR分别为0.61和0.57，95%CI分别为0.37~0.98和0.34~0.98)，IVS4+/+基因型仅降低55岁以下人群ESCC的发病风险(校正OR=0.43，95%CI=0.21~0.85)。此外，单倍型分析发现-9C/IVS4-单倍型增加了食管鳞癌和食管鳞癌的发病风险(OR=1.3 1和1.2 4，95%CI=1.0 8~1.5 8和1.001~1.5 3)。本研究结果提示，PTEN IVS4+/+纯合子在食管鳞癌和宫颈鳞癌的发生中可能起保护作用，而单倍型-9C/IVS4-可能是河北食管鳞癌和宫颈鳞癌高发区人群中的危险因素。
PTEN, as a tumor suppressor gene, plays an important role in regulating cell growth, proliferation, and apoptosis. Two common polymorphisms, -9C/G and IVS4 (-/+), may alter susceptibility to the disease. To test the hypothesis that the genetic variations of PTEN play a role in the etiology of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA), a population-based case-control study was conducted in 350 ESCC patients, 257 GCA patients, and 634 healthy controls from a high-incidence region of Hebei province, China. The PTEN polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). The results showed that the family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age, gender and smoking status adjusted OR = 1.73 and 1.67; 95% CI = 1.29-2.32 and 1.28-2.19, respectively). The overall distribution of the PTEN -9C/G genotype was not significantly different between cancer patients and controls. Compared with the PTEN IVS4-/- genotype, the IVS4+/+ genotype significantly decreased the risk of ESCC and GCA development, the adjusted OR was 0.64 (95% CI = 0.44-0.94) and 0.63 (95% CI = 0.41-0.98), respectively. Stratification analysis by gender, age, smoking status and family history of UGIC showed that the PTEN IVS4-/+ genotype only reduced the risk of ESCC (adjusted OR = 0.55, 95%CI = 0.34-0.90) among subjects with family history of UGIC. While the IVS4+/+ genotype decreased the susceptibility to both ESCC and GCA (adjusted OR = 0.61 and 0.57, 95% CI = 0.37-0.98 and 0.34-0.98, respectively) among male subjects, the IVS4+/+ genotype only decreased the risk of ESCC development among subjects younger than 55 years (adjusted OR = 0.43, 95% CI = 0.21-0.85). In addition, the haplotype analysis found that the -9C/IVS4- haplotype increased the risk of developing ESCC and GCA (OR = 1.31 and 1.24, 95% CI = 1.08-1.58 and 1.001-1.53). Our results suggested that the PTEN IVS4+/+ homozygote may play a protective role in the development of ESCC and GCA, while the haplotype -9C/IVS4- might be the risk factor of the development of ESCC and GCA in the high incidence region population of Hebei province, China.