Epidemiological studies on the distribution and determinants of biliary tract cancer

Abstract

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.

Role of nicotine in gallbladder carcinoma: A preliminary report

“…Gallbladder carcinoma is an aggressive tumor with poor prognosis. In the last three decades a multifactorial causation hypothesis of this disease has evolved through quality research indicating an interplay of genetic and environmental factors . Nicotine is a potent carcinogen of cigarette smoke and tobacco.…”

Risk factors for gallbladder cancer development in northern India: A gallstones-matched, case–control study

“…In the 1970s, Niigata Prefecture had the highest incidence of GBC for both sexes in Japan 4 . Researchers hypothesized a multifactorial cause, including the presence of gallstones or cholecystitis in addition to region-specific environmental factors.…”

“…Researchers hypothesized a multifactorial cause, including the presence of gallstones or cholecystitis in addition to region-specific environmental factors. The results of epidemiological studies provided compelling evidence that conducting risk management, after identifying the modifiable risk factors, reduced GBC incidence and mortality in Niigata Prefecture 4 . Thus, the same methods may be applied in other countries exhibiting a high incidence of GBC.…”