EPIDEMIOLOGY AND BIOSTATISTICS DIVISION

20.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 factors. Several epidemiological projects are currently in progress.
Foods and Nutrients in the Etiology of Human Cancer (Nutritional Epidemiology)

    The division has 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 will be followed-up for 10 years or more. As of November, 2000, 6,047 deaths and 5,259 incident cancers had been documented and a 10 year follow-up survey had been conducted for approximately 50,000 subjects with an 84% response rate. Diabetes prevalence was estimated by plasma glucose criteria combined with standardized measurement of HbA1c on Miyako island, one of the JPHC study areas.⁽²¹²⁾
    As several prospective studies, including the JPHC study, demonstrated a J-shaped curve for the relation between alcohol consumption and all-cause mortality, this association has been reviewed in published articles with regard to cause of death, especially cardiovascular mortality.⁽²¹³⁾ Under- and over-reporting of energy intake in relation to body mass index (BMI) were examined by using 24-hour urinary sodium and potassium as biomarkers. The relative underreporting of energy intake and the percentage of under-reporters increased with increasing BMI.⁽²¹⁴⁾
Environmental and Genetic Interaction in the Etiology of Human Cancer (Molecular Epidemiology)

    Two case-control studies of gastric cancer in Japanese Brazilians and Brazilians not of Japanese ancestry in Sao Paulo were conducted to clarify the roles of genetic susceptibility and environmental carcinogenesis. Although the ethnic differences in Cytochrome P450 2E1 (Cyp2E1) RsaI polymorphism were more striking than those seen in the case-control studies, the variant type was associated with reduced risk of gastric cancer in the non-Japanese group. No statistically significant interactions with environmental factors, such as smoking and meat consumption, were observed.⁽²¹⁵⁾ Ethnic differences in the association between serum pepsinogen levels and gastric cancer status were examined in the same case-control studies. A low level of serum pepsinogen I was associated with gastric cancer in both groups.⁽²¹⁶⁾
    The hOGG1 gene may contribute to further understanding of the relation between oxidative DNA damage and carcinogenesis. A real-time PCR technique was used to determine mRNA levels in peripheral blood cells to assess the possibility of using hOGG1 mRNA as a biomarker in epidemiological studies. The interindividual variation was larger than the intraindividual variation, which suggests potential biomarkers for individual oxidative stress.⁽²¹⁷⁾ The aromatic DNA adduct level in coke-oven workers was examined in relation to exposure, lifestyle and genetic polymorphism of metabolic enzymes. Genetic polymorphisms of Cytochrome P4501A1 and N-acetyltransferase 2 affected the adduct level.⁽²¹⁸⁾
An Epidemiological Evaluation of Cancer Prevention

    The available evidence suggests that the risk of stomach 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 carcinogenesis has progressed to the sixth year for individuals with chronic atrophic gastritis. The effects of three-month oral supplementation of beta-carotene and vitamin C on serum levels were investigated in the participants of a preceding pilot study. Serum beta-carotene gradually increased during the study, whereas serum ascorbic acid reached a steady-state at the one-month point.⁽²¹⁹⁾ Another randomized controlled trial to assess the effectiveness of dietary modification (less salt and more vitamin C and carotene) has progressed to the third year for 550 residents in a high risk area for gastric cancer. The intervention method in this trial was also evaluated for men at high risk of coronary heart disease.⁽²²⁰⁾
Epidemiological and biostatistical support for basic and clinical research

    Epidemiological and biostatistical support has been provided for prognostic and clinical analysis of cancers of the large intestine,⁽¹⁹⁹⁾ breast,⁽¹⁹⁸⁾ larynx⁽²⁰⁴⁾ and lung.⁽²⁰²⁾




20.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 factors. Several epidemiological projects are currently in progress. Foods and Nutrients in the Etiology of Human Cancer (Nutritional Epidemiology) The division has 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 will be followed-up for 10 years or more. As of November, 2000, 6,047 deaths and 5,259 incident cancers had been documented and a 10 year follow-up survey had been conducted for approximately 50,000 subjects with an 84% response rate. Diabetes prevalence was estimated by plasma glucose criteria combined with standardized measurement of HbA1c on Miyako island, one of the JPHC study areas.⁽²¹²⁾ As several prospective studies, including the JPHC study, demonstrated a J-shaped curve for the relation between alcohol consumption and all-cause mortality, this association has been reviewed in published articles with regard to cause of death, especially cardiovascular mortality.⁽²¹³⁾ Under- and over-reporting of energy intake in relation to body mass index (BMI) were examined by using 24-hour urinary sodium and potassium as biomarkers. The relative underreporting of energy intake and the percentage of under-reporters increased with increasing BMI.⁽²¹⁴⁾ Environmental and Genetic Interaction in the Etiology of Human Cancer (Molecular Epidemiology) Two case-control studies of gastric cancer in Japanese Brazilians and Brazilians not of Japanese ancestry in Sao Paulo were conducted to clarify the roles of genetic susceptibility and environmental carcinogenesis. Although the ethnic differences in Cytochrome P450 2E1 (Cyp2E1) RsaI polymorphism were more striking than those seen in the case-control studies, the variant type was associated with reduced risk of gastric cancer in the non-Japanese group. No statistically significant interactions with environmental factors, such as smoking and meat consumption, were observed.⁽²¹⁵⁾ Ethnic differences in the association between serum pepsinogen levels and gastric cancer status were examined in the same case-control studies. A low level of serum pepsinogen I was associated with gastric cancer in both groups.⁽²¹⁶⁾ The hOGG1 gene may contribute to further understanding of the relation between oxidative DNA damage and carcinogenesis. A real-time PCR technique was used to determine mRNA levels in peripheral blood cells to assess the possibility of using hOGG1 mRNA as a biomarker in epidemiological studies. The interindividual variation was larger than the intraindividual variation, which suggests potential biomarkers for individual oxidative stress.⁽²¹⁷⁾ The aromatic DNA adduct level in coke-oven workers was examined in relation to exposure, lifestyle and genetic polymorphism of metabolic enzymes. Genetic polymorphisms of Cytochrome P4501A1 and N-acetyltransferase 2 affected the adduct level.⁽²¹⁸⁾ An Epidemiological Evaluation of Cancer Prevention The available evidence suggests that the risk of stomach 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 carcinogenesis has progressed to the sixth year for individuals with chronic atrophic gastritis. The effects of three-month oral supplementation of beta-carotene and vitamin C on serum levels were investigated in the participants of a preceding pilot study. Serum beta-carotene gradually increased during the study, whereas serum ascorbic acid reached a steady-state at the one-month point.⁽²¹⁹⁾ Another randomized controlled trial to assess the effectiveness of dietary modification (less salt and more vitamin C and carotene) has progressed to the third year for 550 residents in a high risk area for gastric cancer. The intervention method in this trial was also evaluated for men at high risk of coronary heart disease.⁽²²⁰⁾ Epidemiological and biostatistical support for basic and clinical research Epidemiological and biostatistical support has been provided for prognostic and clinical analysis of cancers of the large intestine,⁽¹⁹⁹⁾ breast,⁽¹⁹⁸⁾ larynx⁽²⁰⁴⁾ and lung.⁽²⁰²⁾