2001 Fiscal Year Final Research Report Summary
A case-control study of hepatocellular carcinoma in relation to interaction between genetic polymorphisms of drug metabolizing enzymes and drinking/smoking habits
| Project/Area Number |
11670344
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Saga Medical School (2000-2001)
Kyushu University (1999) |
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Principal Investigator |
TANAKA Keitaro Saga Medical School, Faculty of Medicine, Professor, 医学部, 教授 (50217022)
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| Co-Investigator(Kenkyū-buntansha) |
KIYOHARA Chikako Kyushu University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究院, 講師 (00169963)
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| Project Period (FY) |
1999 – 2000
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| Keywords | hepatocellular carcinoma / case-control study / genetic polymorphism / cytochrome P450 / N-acetyltransferase / alcohol / smoking / 喫煙 |
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| Research Abstract |
Although hepatitis C (HG) and hepatitis B (HB) viruses represent two major causative agents of hepatocellular carcinoma (HCC) in Japan, potential modifying effects of genotypes of drug metabolizing enzymes, such as cytochrome P450 (CYP) and N-acetyltransferase (NAT), on HCC risk have been suggested. We examined whether CYP2E1 and NAT2 polymorphisms were associated with HCC, and whether each polymorphism interacted with drinking and smoking habits in hepatocarcinogenesis. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (CYP2E 1 : Rsal polymorphism in the 5'-flanking region ; NAT2 : Asp718/BamHI/TaqI polymorphism in the coding region near the 3' end) on peripheral leukocyte DNA from 41 incident cases with HCC (71 % male, 80 % HC+, 17 % HB+) and 104 hospital controls with various minor disorders (71% male, 8% HC+, 2% HB+). The cl/cl, cl/c2, and c2/c2 genotypes ofCYP2E1 were found in 73 %, 22 %, and 5 % of cases, as compared with 63 %, 35 %, and 2 % of controls; theodds ratio (OR) for the cl/cl genotype vs. others was 1.6 (95 %CI 0.7 - 3.5). The risk for the cl/cl genotype was elevated substantially among males with heavy drinking history (OR = 9.0), but not among males without such a history (OR = 0.9, P for interaction = 0.09). Similar interaction between the cl/cl genotype and current smoking was observed (Ors: 4.3 vs. 0.8). Overall, NAT2 polymorphism was not associated with HCC risk, yet the rapid acetylator genotype tended to show higher risk among current smokers (OR = 1.9) than among never/past smokers (OR = 0.8). CYP2E1 and NAT2 polymorphisms may play additional roles in alcohol- and smoking-related hepatocarcinogenesis.
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