18. 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. In this respect, several epidemiological projects are currently in progress, including cross-sectional, case-control, cohort and intervention studies. In addition, collaborative studies in the field of clinical and basic sciences are conducted by providing statistical design, analysis and data processing support.

Etiological Roles of Foods and Nutrients in Cancer

Diet has been implicated as playing etiological roles in cancer occurrence and as contributing to 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, 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. Among 60,000 cohort members from 5 areas with a 6 year follow-up, 1,300 deaths, 1,100 incident cancers and 3,000 lost to follow-up had been documented as of December 31, 1995. As the dietary questionnaire commonly used in epidemiological studies in Japan has an inherent limitation in estimating the dietary intakes of individuals, a semi-quantitative food frequency questionnaire allowing estimation of long-term average nutrient intakes has been developed based on an analysis of dietary data collected from the regions in which the prospective study was conducted.⁽¹⁷⁹⁾ This questionnaire includes items concerning the average consumption frequencies of 138 foods as well as 14 supplementary questions on qualitative aspects of the diet. The questionnaire was distributed to 55,000 cohort members who had been followed for 5 years and 43,000 (78%) responded. The major nutrients, including total energy and vitamin C, were calculated in our division and reported to all responders. The four 7-day food records and two blood and urine samples from 250 subjects were collected and analyzed to evaluate the reproducibility and validity of this questionnaire. In addition, the influence of cigarette smoking and alcohol consumption on plasma carotenoid levels^(180,181) and the effects of human diets consumed in two cohort areas on rat hepatic drug-metabolizing and antioxidant enzyme systems⁽¹⁸²⁾ were investigated.

Environmental and Genetic Interaction in the Etiology of Human Cancer

Patterns of cancer incidence vary according to ethnicity and therefore change with migration which results in intermingling with other populations. These observations suggest an interaction between environmental and genetic factors in cancer occurrence. The division has been conducting several epidemiological studies in Brazil, a multi-ethnic nation with 1.2 million people of Japanese ancestry.⁽¹⁸³⁾ A case-control study of gastric cancer has collected lifestyle questionnaires and blood components from 101 Japanese and 250 non-Japanese cases and their controls in the Sao Paulo area. The associations with dietary factors were analyzed and serum pepsinogen I and II and Helicobactor pylori antibody levels were measured.

An Epidemiological Evaluation of Cancer Prevention Methods

Practical prevention strategies are generally based on total evidence obtained from observational epidemiological studies, experimental animal studies and mechanistic interpretation. An evaluation based on intervention studies is, however, essential before recommending a strategy to the general public. 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 vitamin C and beta-carotene. After confirming the feasibility of a large-scale population-based intervention study by conducting a small pilot study among participants of a health check-up program in a hospital,⁽¹⁸⁴⁾ a randomized controlled trial to assess the effectiveness of vitamin C and beta-carotene supplementation on gastric cancer incidence was initiated for individuals with chronic atrophic gastritis in a district where the mortality rate is one of the highest in Japan. In the first year of the study, 439 (73%) out of 602 eligible subjects agreed to participate in the trial and started to take one of four possible regimens based on a two-by-two factorial design with two levels of vitamin C (50 or 500 mg/day) and beta-carotene (0 or 15 mg/day). Most participants continued to take the supplements till January 1996. However, after a press release by the U.S. NCI regarding its unfavorable effect, beta-carotene supplementation was halted and 300 remained in the vitamin C trial.

List of papers from this division

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