EPIDEMIOLOGY AND BIOSTATISTICS DIVISION

24.EPIDEMIOLOGY AND BIOSTATISTICS DIVISION

    The Epidemiology and Biostatistics 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 a population-based prospective study on diet and cancer (JPHC Study) in collaboration with the Cancer Information and Epidemiology Division and the National Cardiovascular Center, in which approximately 140,000 individuals from 11 public health center areas will be followed-up for 20 years. A total of 9,386 deaths and 7,834 cancers had been documented. Several basic investigations were conducted to validate the quality of the JPHC study. Two kinds of food frequency questionnaire (FFQ)s were used in the baseline and 5-year follow-up survey, and these instruments have been validated against a 28- or 14-day dietary record (DR) and related biomarkers. The methodological description ^(272-²⁷⁴⁾, validity data of main nutrients ⁽²⁷⁵⁾, food groups ⁽²⁷⁶⁾, fatty acid ⁽²⁷⁷⁾, carotenoids and vitamin C ⁽²⁷⁸⁾, selenium ⁽²⁷⁹⁾, folate and vitamin B group ⁽²⁸⁰⁾, sodium and potassium ⁽²⁸¹⁾, dietary fiber ⁽²⁸²⁾ and reproducibility of the data ⁽²⁸³⁾ were documented for the FFQ used in the 5-year follow-up survey, as well as the validity and reproducibility of the data for the FFQ used in the baseline survey ⁽²⁸⁴⁾. Both seasonal misclassification of individuals with respect to their usual vitamin C intake and required sample size can be substantially reduced by asking subjects to report high-season intake of fruit and vegetables in the JPHC study ⁽²⁸⁵⁾. Blood and health examination data were collected from the participants in the basic health examination in the JPHC study. Several background characteristics were different between the participants and non-participants, and these differences might cause a selection bias that limits the application of the results to only participants ⁽²⁸⁶⁾. Lifestyle factors that were assessed in the baseline questionnaire were examined with relation to subsequent risk of mortality and cancer incidence. Frequent miso soup and isoflavone consumption was associated with a reduced risk of breast cancer. Approximately half of the colorectal cancer cases may be preventable by tobacco and alcohol controls in middle-aged and elderly Japanese men ⁽²⁸⁷⁾. An inverse association between coffee consumption and the risk of type 2 diabetes mellitus among white Europeans was reported, and similar results among the Japanese group extracted from the JPHC study were introduced ⁽²⁸⁸⁾. Various dietary factors in relation to the presence of atrophic gastritis among Helicobacter pylori-infected subjects was analyzed among sub-samples of the JPHC study, suggesting that the dietary habits of consumers of traditional Japanese foods may play a role in the development of atrophic gastritis after H. pylori infection ⁽²⁸⁹⁾.
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 and a low consumption of salted foods. A randomized controlled trial to assess the effectiveness of vitamin C supplementation on gastric cancer has progressed to the ninth year for individuals with chronic atrophic gastritis. Five-year vitamin C supplementation induced a remarkable increase in serum vitamin C concentration, and our intervention program appeared to have no effect on dietary vitamin C intake ⁽²⁹⁰⁾. The difference in the change of the PGI/II ratio between baseline and after 5-year follow up was statistically significant between the intervention groups among those who completed the supplementation. Vitamin C supplementation may protect against progression of gastric mucosal atrophy ⁽²⁹¹⁾. Another randomized controlled trial to assess the effectiveness of dietary modification (less salt and more vitamin C and carotene) completed its intervention program for 550 residents in a high risk area for gastric cancer. The present dietary intervention strategy effectively decreased sodium and increased carotene and vitamin C intakes, although the former was more distinct ⁽²⁹²⁾. The effectiveness of the dietary counseling system was assessed and verified with a diet history questionnaire ⁽²⁹³⁾.
Epidemiological Study on Japanese Brazilians (Sao Paulo - Japan Cancer Study)

    The ethnic differences in cancer occurrence suggest an interaction between environmental 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. Two case-control studies of gastric cancer in Japanese Brazilians and Brazilians not of Japanese ancestry in Sao Paulo have been conducted to clarify the role of genetic susceptibility and environmental carcinogenesis. The usefulness of serology against H. pylori CagA as a biomarker to identify high-risk individuals for non-cardia gastric cancer (ncGC) remains unclear. Investigation of the ethnic difference among the two sets of case-control subjects showed that the CagA-Ab could be a useful marker for ncGC, independently of ethnicity ⁽²⁹⁴⁾.
Epidemiological Study on Endocrine Disrupting Chemicals

    To examine the health effects of endocrine disrupting chemicals, some preliminary studies were conducted. A cross-sectional study in coke-oven workers employed at an iron-steel factory was conducted to investigate the interaction between environmental and genetic factors. In the high-risk group of exposure to polycyclic aromatic hydrocarbons (PAHs), genetic polymorphisms of CYP1A1 and NAT2 were involved with leukocyte DNA adducts ⁽²⁹⁵⁾. It was not clear if PAHs exposure would induce oxidative DNA damage ⁽²⁹⁶⁾.
Other Epidemiological Studies

    A case-control study in an agricultural area of Japan suggested that cruciferous vegetables decrease the risk of both stomach and colorectal cancer, and that mushrooms are associated with a decreased risk of stomach cancer ⁽²⁹⁷⁾. Allelle frequencies of single nucleotide polymorphisms (SNPs) in 40 candidate genes were shown for population-based Japanese random samples ⁽²⁹⁸⁾. To store DNA samples, a DNA chip which can be stored at -4 degrees C for 2 years was developed. The chip can be used as template DNA during the polymerase chain reaction (PCR) process ⁽²⁹⁹⁾. Using the latest reports on cancer incidence in Japan in 1998, the probability of developing cancer in the entire life span of Japanese subjects was investigated ⁽³⁰⁰⁾. A population-based prospective study to follow 5,885 residents for 14 years showed that frequent fresh fish consumption, irrespective of the cooking method, may reduce the risk of lung cancer ⁽³⁰¹⁾. Reproducibility of the FFQ in a Korean study was verified ⁽³⁰²⁾.




24.EPIDEMIOLOGY AND BIOSTATISTICS DIVISION



	The Epidemiology and Biostatistics 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 a population-based prospective study on diet and cancer (JPHC Study) in collaboration with the Cancer Information and Epidemiology Division and the National Cardiovascular Center, in which approximately 140,000 individuals from 11 public health center areas will be followed-up for 20 years. A total of 9,386 deaths and 7,834 cancers had been documented. Several basic investigations were conducted to validate the quality of the JPHC study. Two kinds of food frequency questionnaire (FFQ)s were used in the baseline and 5-year follow-up survey, and these instruments have been validated against a 28- or 14-day dietary record (DR) and related biomarkers. The methodological description ^(272-²⁷⁴⁾, validity data of main nutrients ⁽²⁷⁵⁾, food groups ⁽²⁷⁶⁾, fatty acid ⁽²⁷⁷⁾, carotenoids and vitamin C ⁽²⁷⁸⁾, selenium ⁽²⁷⁹⁾, folate and vitamin B group ⁽²⁸⁰⁾, sodium and potassium ⁽²⁸¹⁾, dietary fiber ⁽²⁸²⁾ and reproducibility of the data ⁽²⁸³⁾ were documented for the FFQ used in the 5-year follow-up survey, as well as the validity and reproducibility of the data for the FFQ used in the baseline survey ⁽²⁸⁴⁾. Both seasonal misclassification of individuals with respect to their usual vitamin C intake and required sample size can be substantially reduced by asking subjects to report high-season intake of fruit and vegetables in the JPHC study ⁽²⁸⁵⁾. Blood and health examination data were collected from the participants in the basic health examination in the JPHC study. Several background characteristics were different between the participants and non-participants, and these differences might cause a selection bias that limits the application of the results to only participants ⁽²⁸⁶⁾. Lifestyle factors that were assessed in the baseline questionnaire were examined with relation to subsequent risk of mortality and cancer incidence. Frequent miso soup and isoflavone consumption was associated with a reduced risk of breast cancer. Approximately half of the colorectal cancer cases may be preventable by tobacco and alcohol controls in middle-aged and elderly Japanese men ⁽²⁸⁷⁾. An inverse association between coffee consumption and the risk of type 2 diabetes mellitus among white Europeans was reported, and similar results among the Japanese group extracted from the JPHC study were introduced ⁽²⁸⁸⁾. Various dietary factors in relation to the presence of atrophic gastritis among Helicobacter pylori-infected subjects was analyzed among sub-samples of the JPHC study, suggesting that the dietary habits of consumers of traditional Japanese foods may play a role in the development of atrophic gastritis after H. pylori infection ⁽²⁸⁹⁾. 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 and a low consumption of salted foods. A randomized controlled trial to assess the effectiveness of vitamin C supplementation on gastric cancer has progressed to the ninth year for individuals with chronic atrophic gastritis. Five-year vitamin C supplementation induced a remarkable increase in serum vitamin C concentration, and our intervention program appeared to have no effect on dietary vitamin C intake ⁽²⁹⁰⁾. The difference in the change of the PGI/II ratio between baseline and after 5-year follow up was statistically significant between the intervention groups among those who completed the supplementation. Vitamin C supplementation may protect against progression of gastric mucosal atrophy ⁽²⁹¹⁾. Another randomized controlled trial to assess the effectiveness of dietary modification (less salt and more vitamin C and carotene) completed its intervention program for 550 residents in a high risk area for gastric cancer. The present dietary intervention strategy effectively decreased sodium and increased carotene and vitamin C intakes, although the former was more distinct ⁽²⁹²⁾. The effectiveness of the dietary counseling system was assessed and verified with a diet history questionnaire ⁽²⁹³⁾. Epidemiological Study on Japanese Brazilians (Sao Paulo - Japan Cancer Study) The ethnic differences in cancer occurrence suggest an interaction between environmental 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. Two case-control studies of gastric cancer in Japanese Brazilians and Brazilians not of Japanese ancestry in Sao Paulo have been conducted to clarify the role of genetic susceptibility and environmental carcinogenesis. The usefulness of serology against H. pylori CagA as a biomarker to identify high-risk individuals for non-cardia gastric cancer (ncGC) remains unclear. Investigation of the ethnic difference among the two sets of case-control subjects showed that the CagA-Ab could be a useful marker for ncGC, independently of ethnicity ⁽²⁹⁴⁾. Epidemiological Study on Endocrine Disrupting Chemicals To examine the health effects of endocrine disrupting chemicals, some preliminary studies were conducted. A cross-sectional study in coke-oven workers employed at an iron-steel factory was conducted to investigate the interaction between environmental and genetic factors. In the high-risk group of exposure to polycyclic aromatic hydrocarbons (PAHs), genetic polymorphisms of CYP1A1 and NAT2 were involved with leukocyte DNA adducts ⁽²⁹⁵⁾. It was not clear if PAHs exposure would induce oxidative DNA damage ⁽²⁹⁶⁾. Other Epidemiological Studies A case-control study in an agricultural area of Japan suggested that cruciferous vegetables decrease the risk of both stomach and colorectal cancer, and that mushrooms are associated with a decreased risk of stomach cancer ⁽²⁹⁷⁾. Allelle frequencies of single nucleotide polymorphisms (SNPs) in 40 candidate genes were shown for population-based Japanese random samples ⁽²⁹⁸⁾. To store DNA samples, a DNA chip which can be stored at -4 degrees C for 2 years was developed. The chip can be used as template DNA during the polymerase chain reaction (PCR) process ⁽²⁹⁹⁾. Using the latest reports on cancer incidence in Japan in 1998, the probability of developing cancer in the entire life span of Japanese subjects was investigated ⁽³⁰⁰⁾. A population-based prospective study to follow 5,885 residents for 14 years showed that frequent fresh fish consumption, irrespective of the cooking method, may reduce the risk of lung cancer ⁽³⁰¹⁾. Reproducibility of the FFQ in a Korean study was verified ⁽³⁰²⁾.