胆道癌の分布と決定因子に関する疫学的研究

Epidemiological studies on the distribution and determinants of biliary tract cancer.

• Masaharu Yamamoto

抄録

私は、同僚の協力を得て、約19年前から日本とチリで胆嚢癌、肝外胆管癌を含む胆道癌（BTC）の疫学的研究を行っています。特に女性の胆嚢がんの死亡率が高いクラスター化した地域は、日本では米の生産で有名な場所や県に対応していることがわかった。胆石や胆嚢炎などの既知の危険因子の役割を検討したが、これらの地域のGBCの死亡率の高さに関与する単一の因子はなかった。米生産仮説」と呼ばれる作業仮説が立てられ、この初期仮説は新しい多因子因果関係仮説に置き換えられた。遺伝的感受性があり、過去に胆石や胆嚢炎の既往歴があり、農薬などの地理的に特殊な環境因子にさらされている人にGBCが発生しやすいというものである。様々な分析研究に基づいて、ある農薬がGBCの発生に関与していると結論づけられている。本稿執筆時点では、この仮説を否定する証拠は得られていない。また、GBCの死亡率が世界で最も高いチリで国際共同研究を行った。チリ人の胆汁は日本人の胆汁よりも高い変異原性を有しており、便秘の既往歴があったり、赤唐辛子を食べる習慣のあるチリ人は、胆石がある場合、GBCを発症するリスクが高いことがわかった。また、p53の変異原性には地域差が認められた。

With the help of my colleagues, I have been conducting epidemiological studies on biliary tract cancer (BTC), including gallbladder cancer (GBC) and extrahepatic bile duct cancer (BDC), in Japan and Chile for about 19 years. Clustered areas with high mortality rates, especially for female GBC were found to correspond with places or prefectures in Japan that were famous for rice production. The roles of known risk factors, such as gallstones and cholecystitis, were examined, but no single factor was implicated in the high mortality rates for GBC in these areas. A working hypothesis, called the "rice production hypothesis" was formulated; this initial hypothesis was replaced by a new multifactorial causation hypothesis: GBC is more likely to occur in individuals with a genetic susceptibility and a past history of gallstones or cholecystitis who are exposed to geographically specific environmental factors, such as agricultural chemicals. On the basis of various analytical studies, it is concluded that a certain agricultural chemical was responsible for the occurrence of GBC. At the time of writing, no evidence has been obtained to disprove our hypothesis. We have also conducted international collaborative studies in Chile, which has the highest mortality rate for GBC in the world. Bile from Chileans was found to have a higher mutagenic activity than that from Japanese subjects; Chileans with a history of constipation or a habit of consuming red chilli pepper had a high risk of developing GBC, if they also had gallstone(s). The presence of a regional difference in p53 mutagenesis was also observed.