title: Insulin-like growth factor 2 hypomethylation of blood leukocyte DNA is associated with gastric cancer risk.
abstract: To determine whether or not the methylation status of blood leukocyte DNA can be used as a surrogate marker of the risk for cancer, we quantitatively determined the methylation levels of insulin-like growth factor 2 (IGF2) and TUSC3 in 299 gastric cancer cases, and 299 age- and gender-matched controls. The IGF2 methylation levels in blood leukocyte DNA of the cases were lower than those of the healthy controls and there was a significant trend of increasing gastric cancer risk with decreasing methylation level of IGF2. Patients with hypermethylated IGF2 in blood leukocyte DNA showed a significantly better survival rate than those with hypomethylated IGF2, indicating that the IGF2 methylation level in blood leukocyte DNA can be a possible marker not only of the risk for but also of the prognosis of gastric cancer. In contrast, the TUSC3 methylation level in blood leukocyte DNA was higher in the cases than in the healthy controls, but the difference was not significant. The past lifestyle and clinicopathological characteristics of the participants were analyzed for any relationship with the methylation level. With aging and smoking, methylation of IGF2 and TUSC3 decreased and increased in blood leukocyte DNA, respectively. These results indicate that the methylation level of IGF2 in blood leukocyte DNA may be used as an important surrogate marker of the risk for gastric cancer.
authors.affiliation: Department of Molecular Oncology, Tokyo Medical and Dental University, Tokyo, Japan. yuasa.monc@tmd.ac.jp
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Yuasa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nagasaki
authors.forename: Isao
authors.initials: I
authors.lastname: Oze
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yoshida
authors.forename: Kouhei
authors.initials: K
authors.lastname: Shitara
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
authors.forename: Satoyo
authors.initials: S
authors.lastname: Hosono
authors.forename: Miki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Kai-Feng
authors.initials: KF
authors.lastname: Pan
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: You
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000097:blood* / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C035170:IGF2 protein, human; D008565:Membrane Proteins; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins; D007335:Insulin-Like Growth Factor II