2004 Fiscal Year Final Research Report Summary
Genome-wide analyses to identify genes involved in gastric cancer
| Project/Area Number |
12212002
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | International Medical Center of Japan (2001-2004)
Kyushu University (2000) |
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Principal Investigator |
SASAZUKI Tekehiko International Medical Center of Japan, President, 総長 (50014121)
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| Co-Investigator(Kenkyū-buntansha) |
ARIMURA Yoshiaki sapporo medical school, Assistant Professor, 医学部, 助手 (80305218)
NAISHIRO Yasuyoshi sapporo medical school, Assistant Professor, 医学部, 助手 (80347161)
INOKO Hidetoshi tokai university, Professor, 医学部, 教授 (10101932)
YOKOTA Jun national cancer center, research institute, Chief, 部長 (10191503)
YAMAMOTO Ken International Medical Center of Japan, Associate Professor, 生体防御医学研究所, 助教授 (60274528)
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| Project Period (FY) |
2000 – 2004
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| Keywords | gastric cancer / genome / polymorphism / linkage / association / SNP / microsatellite |
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| Research Abstract |
Identification of genes predisposing to cancer is an essential step toward a better understanding of molecular events underlying tumorigenesis and for a more pertinent clinical management of patients. To search for regions of human genome containing gastric cancer-susceptibility genes, we did a genome-wide screen in 170 affected sibpairs using 392 microsatellite markers spanning the entire genome. Nonparametric linkage analysis of the entire data set identified four regions, Ip32, 2q33-q35, I1p13-p14 and 21q21, showing evidence for linkage with multipoint LOD score 【greater than or equal】1.18 (P 【less than or equal】0.01). The signal of linkage to 2q33-q35 increased to a multipoint and two-point LOD score 3.61 and 2.93, respectively in an analysis of a subgroup with proximal gastric cancer. Since chromosome 21q have been reported to show LOH frequently in gastric cancer in Japanese, we further analyzed 70 expressing genes on this candidate chromosome using sporadic cases by marker SNPs. We found unknown but the structure is related to HSP70 which is shown to be involved in carcinogenesis of several types of cancer. In addition, we genotyped SNPs in 41 candidate genes which have been suggested to be related to gastric carcinogenesis. We found significant association between ATM and female cases. According to the threshold theory of a multifactorial trait, heritability of female cases of gastric cancer might be higher than that of male cases. Taken together, STCH and ATM might be important target genes of further analyses to elucidate molecular mechanisms of gastric cancer pathogenesis.
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