EPIDEMIOLOGY AND PREVENTION DIVISION

25.EPIDEMIOLOGY AND PREVENTION DIVISION

    The Epidemiology and Prevention Division has planned and conducted independent and collaborative studies on cancer etiology and prevention, with a special focus on dietary, environmental and genetic factors. Several epidemiological projects are currently in progress.
Population-based Prospective Study (the JPHC Study)

    Diet has been implicated in the etiology of cancer occurrence and in the unique patterns of cancer incidence in Japan. However, epidemiological evidence regarding this issue has been limited. The division has therefore initiated the Japan Public Health Center-based Prospective Study on diet and cancer and cardiovascular disease (JPHC Study) in 1990 in collaboration with 11 public health centers and other institutes, in which approximately 140,000 individuals from 11 areas will be followed-up for 20 years. A total of 10,769 deaths and 9,229 cancers had been documented as of 31 December, 2004.
    Lifestyle factors that were assessed in the baseline questionnaire were examined with relation to subsequent risk of incidence of cancer and other lifestyle-related diseases. The quintile category of salt intake was dose-dependently associated with gastric cancer risk in men, and the frequency categories of highly salted foods such as salted fish roe and salted fish preserves were strongly associated with the risk in both sexes ⁽²⁸⁰⁾. Current smokers presented a significantly increased risk of subsequent cancer occurrence compared with never-smokers, which figures out that 29% of male and 3% of female cancer would be preventable in Japanese middle-aged population by avoidance of smoking ⁽²⁸¹⁾. Among three major dietary patterns identified from factor analysis, the healthy pattern was inversely associated with gastric cancer risk in women but not in men, while the traditional pattern was significantly associated with the increased risk in both sexes, and the Western pattern showed no association ⁽²⁸²⁾. Heavy alcohol consumption was positively associated with risk of total stroke, and light-to-moderate alcohol consumption did not increase the risk of total stroke, and was associated with a lower risk of ischemic stroke and a higher risk of hemorrhagic stroke ⁽²⁸³⁾. Smoking increased risks of total stroke and subarachnoid hemorrhage for men and women and risk of ischemic stroke, either lacunar or large-artery occlusive infarction, for men ⁽²⁸⁴⁾. In men, a U-shaped association between body mass index (BMI) and cancer occurrence was observed, suggesting a very low rather than high BMI has an impact on the total cancer risk in populations with a low average BMI ⁽²⁸⁵⁾. An inverse association between green tea consumption and distal gastric cancer was observed among women ⁽²⁸⁶⁾. Consumption of fish and long chain n-3 polyunsaturated fatty acids (Ln-3 PUFA) showed no association with the colon and rectal cancer risk in this population with high fish consumption ⁽²⁸⁷⁾. Vegetables and fruit intake was not associated with lowered risk of lung cancer.
Gastric Cancer Prevention Trials (Hiraka Study)

    The available evidence suggests that the risk of gastric cancer is increased in individuals with chronic atrophic gastritis and is decreased in those with a high consumption of fruit and vegetables. A randomized controlled trial to assess the effectiveness of vitamin C supplementation for individuals with chronic atrophic gastritis to prevent gastric cancer in a high risk area has progressed to the tenth year. The 5-year vitamin C supplementation had no markedly favourable effects on the serum lipid and lipoprotein profile, although a significant decrease of the mean triacylglycerol concentration was observed in the high-dose group among women with hypertriacylglycerolaemia ⁽²⁸⁸⁾.
    A community-based randomized cross-over trial designed to develop an effective dietary modification tool and system was held in the same area in 1998-2000, and the follow-up survey after the intervention is proceeding.
Epidemiological Study on Japanese Brazilians (Sao Paulo-Japan Cancer Study)

    The ethnic differences in cancer occurrence suggest an interaction between enviromental and genetic factors. The Division has been conducting several epidemiological studies in Brazil, a multi-ethnic nation with 1.2 million people of Japanese ancestry.
    To update cancer mortality pattern of Japanese immigrants in Brazil reported in 1989, we compared the mortality data from 1999-2001 between Japanese in Japan and Japanese immigrants or Brazilians in the state of Sao Paulo, Brazil. Relative to native Japanese, similar mortality ratios of stomach and colorectal cancer were observed for Japan-born residents of Brazil but significantly lower ratios for native Brazilians. Both Japan-born residents and Brazilians had significantly lower mortality ratios for liver, gallbladder and lung cancer, and significantly higher for prostate, cervical and brain and nervous system cancer than native Japanese ⁽²⁸⁹⁾.
Other Epidemiological Studies

    A case-control study of gastric cancer was conducted in Nagano prefecture between 1998 and 2002. Although Helicobactor pylori infection was strongly associated with non-cardia gastric cancer, smoking and frequent intake of miso soup and rice were determined to be risk factors even after adjusting for possible confounding factors including H. pylori infection. No statistically significant interaction between environmental factors and H. pylori infection was detected ⁽²⁹⁰⁾. The association between Ser326Cys hOGG1 genetic polymorphism and gastric cancer was investigated in this case-control study. Overall, neither the hOGG1 Ser/Cys nor the Cys/Cys genotype was associated with risk of gastric cancer, compared with the Ser/Ser genotype. A significant interaction was observed between hOGG1 Ser/Cys or Cys/Cys genotype and atrophic gastritis ⁽²⁹¹⁾.
    A column-switching liquid chromatography-mass spectrometry assay was developed for quantification of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in human hair. The median level of PhIP detected in 42 hair samples was 1184 pg/g hair. The intrapersonal correlation between the first and the second analyses (1-3 month interval) was r=0.85 ⁽²⁹²⁾.
    The relationship between MYH gene polymorphism and gastric cancer was examined. A novel splice-site variant, IVS10-2A > G (c.892-2A > G), was found. No significant increased risk was observed in this variant in a case-control study ⁽²⁹³⁾.
    Epidemiological and biostatistical support has been provided for the analysis of the prevalence of substance abuse in a psychological study ⁽²⁹⁴⁾.




25.EPIDEMIOLOGY AND PREVENTION DIVISION



	The Epidemiology and Prevention Division has planned and conducted independent and collaborative studies on cancer etiology and prevention, with a special focus on dietary, environmental and genetic factors. Several epidemiological projects are currently in progress. Population-based Prospective Study (the JPHC Study) Diet has been implicated in the etiology of cancer occurrence and in the unique patterns of cancer incidence in Japan. However, epidemiological evidence regarding this issue has been limited. The division has therefore initiated the Japan Public Health Center-based Prospective Study on diet and cancer and cardiovascular disease (JPHC Study) in 1990 in collaboration with 11 public health centers and other institutes, in which approximately 140,000 individuals from 11 areas will be followed-up for 20 years. A total of 10,769 deaths and 9,229 cancers had been documented as of 31 December, 2004. Lifestyle factors that were assessed in the baseline questionnaire were examined with relation to subsequent risk of incidence of cancer and other lifestyle-related diseases. The quintile category of salt intake was dose-dependently associated with gastric cancer risk in men, and the frequency categories of highly salted foods such as salted fish roe and salted fish preserves were strongly associated with the risk in both sexes ⁽²⁸⁰⁾. Current smokers presented a significantly increased risk of subsequent cancer occurrence compared with never-smokers, which figures out that 29% of male and 3% of female cancer would be preventable in Japanese middle-aged population by avoidance of smoking ⁽²⁸¹⁾. Among three major dietary patterns identified from factor analysis, the healthy pattern was inversely associated with gastric cancer risk in women but not in men, while the traditional pattern was significantly associated with the increased risk in both sexes, and the Western pattern showed no association ⁽²⁸²⁾. Heavy alcohol consumption was positively associated with risk of total stroke, and light-to-moderate alcohol consumption did not increase the risk of total stroke, and was associated with a lower risk of ischemic stroke and a higher risk of hemorrhagic stroke ⁽²⁸³⁾. Smoking increased risks of total stroke and subarachnoid hemorrhage for men and women and risk of ischemic stroke, either lacunar or large-artery occlusive infarction, for men ⁽²⁸⁴⁾. In men, a U-shaped association between body mass index (BMI) and cancer occurrence was observed, suggesting a very low rather than high BMI has an impact on the total cancer risk in populations with a low average BMI ⁽²⁸⁵⁾. An inverse association between green tea consumption and distal gastric cancer was observed among women ⁽²⁸⁶⁾. Consumption of fish and long chain n-3 polyunsaturated fatty acids (Ln-3 PUFA) showed no association with the colon and rectal cancer risk in this population with high fish consumption ⁽²⁸⁷⁾. Vegetables and fruit intake was not associated with lowered risk of lung cancer. Gastric Cancer Prevention Trials (Hiraka Study) The available evidence suggests that the risk of gastric cancer is increased in individuals with chronic atrophic gastritis and is decreased in those with a high consumption of fruit and vegetables. A randomized controlled trial to assess the effectiveness of vitamin C supplementation for individuals with chronic atrophic gastritis to prevent gastric cancer in a high risk area has progressed to the tenth year. The 5-year vitamin C supplementation had no markedly favourable effects on the serum lipid and lipoprotein profile, although a significant decrease of the mean triacylglycerol concentration was observed in the high-dose group among women with hypertriacylglycerolaemia ⁽²⁸⁸⁾. A community-based randomized cross-over trial designed to develop an effective dietary modification tool and system was held in the same area in 1998-2000, and the follow-up survey after the intervention is proceeding. Epidemiological Study on Japanese Brazilians (Sao Paulo-Japan Cancer Study) The ethnic differences in cancer occurrence suggest an interaction between enviromental and genetic factors. The Division has been conducting several epidemiological studies in Brazil, a multi-ethnic nation with 1.2 million people of Japanese ancestry. To update cancer mortality pattern of Japanese immigrants in Brazil reported in 1989, we compared the mortality data from 1999-2001 between Japanese in Japan and Japanese immigrants or Brazilians in the state of Sao Paulo, Brazil. Relative to native Japanese, similar mortality ratios of stomach and colorectal cancer were observed for Japan-born residents of Brazil but significantly lower ratios for native Brazilians. Both Japan-born residents and Brazilians had significantly lower mortality ratios for liver, gallbladder and lung cancer, and significantly higher for prostate, cervical and brain and nervous system cancer than native Japanese ⁽²⁸⁹⁾. Other Epidemiological Studies A case-control study of gastric cancer was conducted in Nagano prefecture between 1998 and 2002. Although Helicobactor pylori infection was strongly associated with non-cardia gastric cancer, smoking and frequent intake of miso soup and rice were determined to be risk factors even after adjusting for possible confounding factors including H. pylori infection. No statistically significant interaction between environmental factors and H. pylori infection was detected ⁽²⁹⁰⁾. The association between Ser326Cys hOGG1 genetic polymorphism and gastric cancer was investigated in this case-control study. Overall, neither the hOGG1 Ser/Cys nor the Cys/Cys genotype was associated with risk of gastric cancer, compared with the Ser/Ser genotype. A significant interaction was observed between hOGG1 Ser/Cys or Cys/Cys genotype and atrophic gastritis ⁽²⁹¹⁾. A column-switching liquid chromatography-mass spectrometry assay was developed for quantification of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in human hair. The median level of PhIP detected in 42 hair samples was 1184 pg/g hair. The intrapersonal correlation between the first and the second analyses (1-3 month interval) was r=0.85 ⁽²⁹²⁾. The relationship between MYH gene polymorphism and gastric cancer was examined. A novel splice-site variant, IVS10-2A > G (c.892-2A > G), was found. No significant increased risk was observed in this variant in a case-control study ⁽²⁹³⁾. Epidemiological and biostatistical support has been provided for the analysis of the prevalence of substance abuse in a psychological study ⁽²⁹⁴⁾.