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.
seconds ; Gallstones ; Mortality Vital Statistics ; Cancer of Biliary Tract ; Spatial Distribution

PURPOSE: Breast cancer survivors have slightly increased the risk of second primary cancers. Breast, colon, uterine, and ovarian cancers are common secondary cancers in breast cancer survivors. In this study, we assessed the development of second primary cancers of breast cancer survivors in Korea. METHODS: Medical records of patients with breast cancer in 3 tertiary medical institutions were reviewed retrospectively. We evaluated secondary malignancy diagnosed at least 2 months after the breast cancer diagnosis. Based on the International Classification of Disease-9 codes of malignancies, secondary primary breast cancer records were evaluated with person-year adjustment. The standardized incidence ratio (SIR) was assessed using national cancer incidence. RESULTS: A total of 3,444 treatment records were included from 3 medical centers. The cumulative incidence of overall second primary cancers was 2.8% (n = 93). The SIR was significantly higher in all sites (1.56; 95% confidence interval [CI], 1.26–1.91), endometrial cancer (5.65; 95% CI, 2.06–12.31), biliary tract cancer (3.96; 95% CI, 1.19–8.60), and thyroid cancer (2.29; 95% CI, 1.67–3.08). CONCLUSION: The incidence of cancer was higher in breast cancer survivors compared to general population. Surveillance of secondary cancer in this group should be recommended individually considering the benefit related to the prognosis of primary breast cancer.
Biliary Tract Neoplasms ; Breast Neoplasms* ; Breast* ; Classification ; Colon ; Diagnosis ; Early Detection of Cancer ; Endometrial Neoplasms ; Female ; Humans ; Incidence ; Korea ; Medical Records ; Neoplasms, Second Primary* ; Ovarian Neoplasms ; Prognosis ; Retrospective Studies ; Survivors* ; Thyroid Neoplasms

PURPOSE: Breast cancer survivors have slightly increased the risk of second primary cancers. Breast, colon, uterine, and ovarian cancers are common secondary cancers in breast cancer survivors. In this study, we assessed the development of second primary cancers of breast cancer survivors in Korea. METHODS: Medical records of patients with breast cancer in 3 tertiary medical institutions were reviewed retrospectively. We evaluated secondary malignancy diagnosed at least 2 months after the breast cancer diagnosis. Based on the International Classification of Disease-9 codes of malignancies, secondary primary breast cancer records were evaluated with person-year adjustment. The standardized incidence ratio (SIR) was assessed using national cancer incidence. RESULTS: A total of 3,444 treatment records were included from 3 medical centers. The cumulative incidence of overall second primary cancers was 2.8% (n = 93). The SIR was significantly higher in all sites (1.56; 95% confidence interval [CI], 1.26–1.91), endometrial cancer (5.65; 95% CI, 2.06–12.31), biliary tract cancer (3.96; 95% CI, 1.19–8.60), and thyroid cancer (2.29; 95% CI, 1.67–3.08). CONCLUSION: The incidence of cancer was higher in breast cancer survivors compared to general population. Surveillance of secondary cancer in this group should be recommended individually considering the benefit related to the prognosis of primary breast cancer.
Biliary Tract Neoplasms ; Breast Neoplasms* ; Breast* ; Classification ; Colon ; Diagnosis ; Early Detection of Cancer ; Endometrial Neoplasms ; Female ; Humans ; Incidence ; Korea ; Medical Records ; Neoplasms, Second Primary* ; Ovarian Neoplasms ; Prognosis ; Retrospective Studies ; Survivors* ; Thyroid Neoplasms