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.

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 12,059 deaths and 10,117 cancers had been documented as of 31 December, 2005.

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. Subjects who consumed coffee on a daily or almost daily basis had a lower hepatocellular carcinoma risk than those who almost never drank coffee, and the risk decreased with the amount of coffee consumed ⁽²⁶⁵⁾. Smoking women had a higher breast cancer risk than never-active smokers without passive smoking. In premenopausal women, passive smoking increased the risk but not in postmenopausal women ⁽²⁶⁶⁾. Ethanol intake elevates the risk of cancer, especially among smokers. Nearly 13% of cancers among males in this study were due to heavy drinking, to which smoking substantially contributed ⁽²⁶⁷⁾. Among three major dietary patterns identified from factor analysis, the traditional and the Western pattern were positively associated with colon cancer risk in women ⁽²⁶⁸⁾. The association was investigated between reproductive factors, hormone use and the risk of lung cancer among never-smoking women. Both endogenous and exogenous estrogen may be involved in the etiology of lung cancer ⁽²⁶⁹⁾. Vegetables and fruit intake was not associated with the lowered risk of colorectal cancer ⁽²⁷⁰⁾, while a BMI equal to more than 27 increased the risk in men ⁽²⁷¹⁾. Established risk factors for diabetes such as obesity or smoking in Western populations were also identified as predictors of the disease among Japanese. Moderate to high alcohol consumption was positively associated with the increased risk in lean men whose body mass index (BMI) were equal to or less than 22 ⁽²⁷²⁾. Heavy smoking, particularly a large number of cigarettes per day, was associated with an increased risk of suicide ⁽²⁷³⁾. A food frequency questionnaire (FFQ) used in the study was valid for and generalizable to the estimation of folate intake ⁽²⁷⁴⁾.

To develop an evidence-based cancer prevention strategy in terms of lifestyle intervention that is suitable for the Japanese population, a systematic literature review project and some intervention studies are in progress. Based on a systematic review of epidemiological evidence, current tobacco smoking moderately increases the risk (approximately 1.5 times) of total cancer in the Japanese population ⁽²⁷⁵⁾. 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 of Hiraka, Akita prefecture has completed and the data are under analysis. 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. The association between salt, salted food intake and the risk of gastric cancer ⁽²⁷⁶⁾ as well as gastric cancer in Japan ⁽²⁷⁷⁾ was reviewed through accumulated epidemiologic evidence.

The ethnic differences in cancer occurrence suggest an interaction between environmental and genetic factors. Several epidemiologic studies in Brazil, a multi-ethnic nation with 1.2 million people of Japanese ancestry, are in progress. Case-control studies for breast cancer and colonic adenoma are in progress.

A project to evaluate risk of endocrine-disrupting chemicals (EDC) on human health is also in progress. A hospital-based cross-sectional study among Japanese women provides some evidence that serum levels of selected organochlorine compounds are not associated with an increased risk of endometriosis ⁽²⁷⁸⁾, and that codon 185 polymorphism of AhRR, a dioxin receptor repressor gene, was associated with susceptibility to and severity of endometriosis ⁽²⁷⁹⁾, and that the A-allele of HSD17B1, an estradiol-synthesizing enzyme gene, appears to confer a higher risk for endometriosis ⁽²⁸⁰⁾.

A multicenter, hospital-based case-control study in a rural community in Nagano prefecture, where also is a low risk area of gastric and colorectal cancer in Japan, produced the result that, among the genes related to folate metabolism, not MTHFR as in the existing hypothesis but MTRR polymorphism interacted with folate or vitamins in relation to colorectal cancer risk ⁽²⁸¹⁾.

Using a sample of 339 middle-aged, randomly selected Japanese men, 153 polymorphisms of 40 candidate genes were screened to investigate the association with lifestyle factors. The significant variables selected for smoking were OGG1, SLC6a64, EPHX1, ESR1, and CYP17A1 and for drinking, ALDH2 and NUDT1 ⁽²⁸²⁾.

The scalp hair samples and the dietary records from 20 volunteer subjects were examined. The 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine (PhIP) level in the hair was well correlated to the lowest to the highest tertile of the grilled/stirfried meat and fish intake, and can be used as a biological indicator of dietary intake of heterocyclic amines ⁽²⁸³⁾.

Some support was offered to help data analysis of a clinical trial ⁽²⁸⁴⁾, epidemiologic studies ^{(285, 286)}, and a molecular genetic study ⁽²⁸⁷⁾.