| Co-Investigator(Kenkyū-buntansha) |
TAKIGUCHI Shuji Osaka University Medical School of Medicine, Visiting Assistant Professor, 医学系研究科, 寄附講座教員 (00301268)
INOUE Masatoshi Osaka University Medical School of Medicine, Lecturer, 医学系研究科, 講師 (80232560)
SHIOZAKI Hitoshi Osaka University Medical School of Medicine, Assistant Professor, 医学系研究科, 助教授 (70144475)
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| Research Abstract |
For cancers like esophageal cancer, which are closely related to environmental carcinogens in their carcinogenesis pathway, genetic polymorphism of the drug metabolizing genes which activete or detoxify cancinogenic compounds play an important role in determining individual cancer susceptibility. Therefore, we examined genotypes of cytochrome P450(CYP)1A1, 2E1, glutathione S transferase M(GSTM1), N-acetyltransferase 2(NAT2), glutathione S transferase P(GSTP)and compared their gene frequencies among healthy volunteers, patients with esophageal cancer and those with head-and-neck cancer. For esophageal cancer and laryngeal cancer, slow or intermediate acetylator type of NAT2(OR ; 3.0 and 2.7, respectively)and AA type of GSTP(OR ; 8.0 and 2.4, respectively)were found to be a significant risk factor. On the other hand, for pharyngeal cancer, Val/Val type of CYP1A1 was a risk factor(OR ; 5.7). We also analysed genetic polymorphism of acetaldehyde dehydrogenase 2(ALDH2), which catalyses alcohol metabolism. ALDH2 2^*, a variant type, encodes an enzyme with a lower catalytic activity than that encoded by a wild type, ALDH2 1^*. Therefore, more acetaldehyde accumulates in those carrying a variant gene. We found that heterozygotes(1^*/2^*)were significantly more frequently seen in patients with esophageal cancer and those with laryngeal cancer as compared with healthy controls. Next, we analysed expression level of O6-methyl guanine methyltransferase(MGMT)in tumor tissues, which repairs DNA adduct(O6-methyl guanine)generated by carcinogenic compounds. Immunohistochemical study revealed that few esophageal cancers and head and neck cancers showed decreased expression of MGMT.This suggests that MGMT may not have a strong effect on esophageal and head-and-neck carcinogenesis. In conclusion, genotyping of polymorphisms for certain drug-metabolizing genes and alcohol metabolizing genes may help to select high risk group for esophageal and head-and-neck cancer.
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