Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer

被引：0
作者：
机构：
[1] National Cancer Center Research Institute,Genetics Division
[2] 5-1-1 Tsukiji,Department of Health Policy and Management
[3] Chuo-ku,Department of Surgical Oncology
[4] Keio University School of Medicine,Pathology of Clinical Laboratory Division
[5] 35 Shinanomachi,First Department of Pathology
[6] Shinjuku-ku,Department of Surgery
[7] National Cancer Center Hospital,Department of Endoscopy
[8] 5-1-1 Tsukiji,Department of Internal Medicine
[9] Chuo-ku,Department of Molecular Pathology
[10] National Cancer Center Hospital,Department of Internal Medicine
[11] 5-1-1 Tsukiji,Solution Division 4
[12] Chuo-ku,Statistical Genetics Analysis Division
[13] Hamamatsu University School of Medicine,Science Solutions Division
[14] 1-20-1 Handayama,undefined
[15] Hamamatsu-shi,undefined
[16] Iwata City Hospital,undefined
[17] 512-3 Ohkubo,undefined
[18] Iwata-shi,undefined
[19] Nippon Medical School Hospital,undefined
[20] 1-1-5 Sendagi,undefined
[21] Bunkyo-ku,undefined
[22] Aichi Cancer Center Hospital,undefined
[23] 1-1 Kanokoden,undefined
[24] Chikusa-ku,undefined
[25] Shikoku Cancer Center,undefined
[26] 160 Kou,undefined
[27] Minamiumemoto-cho,undefined
[28] Matsuyama-shi,undefined
[29] Hiroshima University Graduate School of Biomedical Sciences,undefined
[30] 1-2-3 Kasumi,undefined
[31] Minami-ku,undefined
[32] Keio University School of Medicine,undefined
[33] 35 Shinanomachi,undefined
[34] Shinjuku-ku,undefined
[35] SNP Research Center,undefined
[36] The Institute of Physical and Chemical Research (RIKEN),undefined
[37] 1-7-22 Suehiro-cho,undefined
[38] Tsurumi-ku,undefined
[39] Bioinfomatics Group,undefined
[40] Research and Development Center,undefined
[41] Hitachi Government and Public Corporation System Engineering Ltd.,undefined
[42] 2-4-18 Toyo,undefined
[43] Koto-ku,undefined
[44] Bio-IT Business Promotion Center,undefined
[45] Solution Development Laboratories,undefined
[46] NEC Corporation,undefined
[47] NEC,undefined
[48] 5-7-1 Shiba,undefined
[49] Minato-ku,undefined
[50] StaGen Co.,undefined
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Nature Genetics | 2008年 / 40卷
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摘要：
Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38–1.89, P = 1.11 × 10−9). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r2 = 0.995, D′ = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56–2.33, P = 8.01 × 10−11). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.
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页码：730 / 740
页数：10
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