Molecular pathological study of individual predisposition to gastric cancer

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The following results were obtained during the above period.1.Mis-sense germline mutation of CDH1 in Japanese familial gastric cancer subjects.2.The investigator clarified that OGG1 polymorphism modified the life style dependent risk of upper GI tract cancer.3.A new method to detect chromosomal instability in pathology archives of gastric cancer was developed. Using this technique the investigator identified a particular feature of gastric cancer with family history, multiplicity, and particular histological type.4.Repair genes such as NEIL1 and MYH were altered both in somatic and germline DNA of gastric cancer with/without family history of cancer. Newly identified polymorphism of MYH is shown to be clearly associated localization alteration.5.A novel LKB1 mutation was identified in Peutz-Jeghers syndrome with gastric cancers.6.Eph /EFN family genes were investigated in gastric and colorectal cancers. Germline and somatic mutation searches were performed expecting the situation for familial prostate and familial hyperplastic colorectal polyposis. Loss of heterozygosity of EPHB2 in colorectal cancer was demonstrated, and EPHA2 expression in gastric cancer was documented. EFNA1 suppressed the growth of EFHA2 expressing gastric cancer cell lines. These genes were demonstrated to interact with Tiam1, which is localized in the candidate area of gastric cancer predispostiion according to sib-pair analyses.7.Extension to searches for germline mutations of candidate genes in familial gastric cancer cases.8.A novel polymorphism in KLK12 was found in gastric cancer patients and alteration in gastric cancer was described.