Humar Bostjan, Graziano Francesco, Cascinu Stefano, Catalano Vincenzo, Ruzzo Anna M, Magnani Mauro, Toro Tumi, Burchill Tudor, Futschik Matthias E, Merriman Tony, Guilford Parry
Cancer Genetics Laboratory, University of Otago, Dunedin, Aotearoa, New Zealand.
Oncogene. 2002 Nov 21;21(53):8192-5. doi: 10.1038/sj.onc.1205921.
Truncating mutations in the gene for the cell to cell adhesion protein E-cadherin are the most consistent genetic alterations observed in sporadic and hereditary diffuse gastric cancer (DGC). In addition to these inactivating mutations, a CDH1 promoter polymorphism at position -160 has been reported to lead to transcriptional downregulation of the gene in vitro. We therefore performed a case-control study to investigate whether this variant is associated with an increased susceptibility to DGC. The frequency of the -160A allele was significantly higher (P<0.005) in 53 diffuse gastric cancer cases compared to 70 matched controls. The odds ratio associated with the A-allele was 2.27 for CA-heterozygotes (95%CI 1.16-4.44) and 7.84 for AA-homozygotes (95%CI 2.89-21.24). Two additional polymorphisms (the 48+6T-->C and the 2076C-->T variant) were genotyped and shown to be equally distributed among cases and controls. Haplotype analysis with the three polymorphisms confirmed an association with disease (P<0.004). However, this analysis suggested the -160C-->A CDH1 promoter polymorphism may be in linkage disequilibrium with a distinct aetiological locus or acts in combination with other functional variants in or near the CDH1 region.
细胞间黏附蛋白E-钙黏蛋白基因的截短突变是散发性和遗传性弥漫性胃癌（DGC）中最一致的基因改变。除了这些失活突变外，据报道，-160位的CDH1启动子多态性会导致该基因在体外转录下调。因此，我们进行了一项病例对照研究，以调查该变体是否与DGC易感性增加有关。与70名匹配对照相比，53例弥漫性胃癌病例中-160A等位基因的频率显著更高（P<0.005）。CA杂合子与A等位基因相关的优势比为2.27（95%CI 1.16-4.44），AA纯合子为7.84（95%CI 2.89-21.24）。另外两个多态性（48+6T→C和2076C→T变体）进行了基因分型，结果显示在病例组和对照组中分布均匀。对这三个多态性进行单倍型分析证实与疾病有关（P<0.004）。然而，该分析表明，-160C→A CDH1启动子多态性可能与一个独特的病因位点处于连锁不平衡状态，或者与CDH1区域内或附近的其他功能变体共同起作用。
