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

被引：328

作者：

Sakamoto, Hiromi ^{[1
]}

Yoshimura, Kimio ^{[1
,2
]}

Saeki, Norihisa ^{[1
]}

Katai, Hitoshi ^{[3
]}

Shimoda, Tadakazu ^{[4
]}

Matsuno, Yoshihiro ^{[4
]}

Saito, Daizo ^{[3
]}

Sugimura, Haruhiko ^{[5
]}

Tanioka, Fumihiko ^{[6
]}

Kato, Shunji ^{[7
]}

Matsukura, Norio ^{[7
]}

Matsuda, Noriko ^{[7
]}

Nakamura, Tsuneya ^{[8
]}

Hyodo, Ichinosuke ^{[9
]}

Nishina, Tomohiro ^{[9
]}

Yasui, Wataru ^{[10
]}

Hirose, Hiroshi ^{[11
]}

Hayashi, Matsuhiko ^{[11
]}

Toshiro, Emi ^{[3
]}

Ohnami, Sumiko ^{[1
]}

Sekine, Akihiro ^{[12
]}

Sato, Yasunori ^{[1
]}

Totsuka, Hirohiko ^{[13
]}

Ando, Masataka ^{[14
]}

Takemura, Ryo ^{[15
]}

Takahashi, Yoriko ^{[16
]}

Ohdaira, Minoru ^{[16
]}

Aoki, Kenichi ^{[16
]}

Honmyo, Izumi ^{[16
]}

Chiku, Suenori ^{[17
]}

Aoyagi, Kazuhiko ^{[1
]}

Sasaki, Hiroki ^{[1
]}

Ohnami, Shumpei ^{[18
]}

Yanagihara, Kazuyoshi ^{[19
]}

Yoon, Kyong-Ah ^{[20
]}

Kook, Myeong-Cherl ^{[20
]}

Lee, Yeon-Su ^{[20
]}

Park, Sook Ryun ^{[20
]}

Kim, Chan Gyoo ^{[20
]}

Choi, Il Ju ^{[20
]}

Yoshida, Teruhiko ^{[1
]}

Nakamura, Yusuke ^{[12
,21
]}

Hirohashi, Setsuo

机构：

[1] Natl Canc Ctr, Inst Res, Div Genet, Chuo Ku, Tokyo 1040045, Japan

[2] Keio Univ, Sch Med, Dept Hlth Policy & Management, Shinjuku Ku, Tokyo 1608582, Japan

[3] Natl Canc Ctr, Dept Surg Oncol, Chuo Ku, Tokyo 1040045, Japan

[4] Natl Canc Ctr, Pathol Clin Lab Div, Chuo Ku, Tokyo 1040045, Japan

[5] Hamamatsu Univ Sch Med, Dept Pathol 1, Hamamatsu, Shizuoka 4313192, Japan

[6] Iwata City Hosp, Iwata, Shizuoka 4388550, Japan

[7] Nippon Med Coll Hosp, Dept Surg, Bunkyo Ku, Tokyo 1138602, Japan

[8] Aichi Canc Ctr Hosp, Dept Endoscopy, Chikusa Ku, Nagoya, Aichi 4648681, Japan

[9] Shikoku Canc Ctr, Dept Internal Med, Matsuyama, Ehime 7910280, Japan

[10] Hiroshima Univ, Grad Sch Biomed Sci, Dept Mol Pathol, Minami Ku, Hiroshima 7348551, Japan

[11] Keio Univ, Sch Med, Dept Internal Med, Shinjuku Ku, Tokyo 1608582, Japan

[12] RIKEN, Inst Phys & Chem Res, SNP Res Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[13] Hitachi Govt & Publ Corp Syst Engn Ltd, Bioinformat Grp, Ctr Res & Dev, Solut Div 4,Koto Ku, Tokyo 1358633, Japan

[14] NEC Corp Ltd, BioIT Business Promot Ctr, Solut Dev Labs, Minato Ku, Tokyo 1088001, Japan

[15] StaGen Co Ltd, Stat Genet Anal Div, Taito Ku, Tokyo 1110051, Japan

[16] Mitsui Knowledge Ind Co Ltd, Chiyoda Ku, Tokyo 1010054, Japan

[17] Mizuho Informat & Res Inst Inc, Sci Solut Div, Chiyoda Ku, Tokyo 1018443, Japan

[18] Natl Canc Ctr, Res Inst, Cent RI Lab, Chuo Ku, Tokyo 1040045, Japan

[19] Natl Canc Ctr, Res Inst, Cent Anim Lab, Chuo Ku, Tokyo 1040045, Japan

[20] Natl Canc Ctr, Res Inst & Hosp, Goyang Si 411764, Gyeonggi Do, South Korea

[21] Univ Tokyo, Ctr Human Genome, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan

来源：

NATURE GENETICS | 2008年 / 40卷 / 06期

关键词：

D O I：

10.1038/ng.152

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

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 x 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 r(2) = 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 x 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.

引用

页码：730 / 740

页数：11

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