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 and in the unique patterns of cancer incidence in Japan. However, the epidemiological evidence for this contention has been limited. The division therefore initiated a cohort study, the Japan Public Health Center-based Prospective Study (JPHC Study), in 1990, in collaboration with 11 public health centers and other institutes, in which approximately 140,000 individuals from 11 areas are scheduled to be followed up for 20 years. A total of 14,000 deaths, 12,700 cases of cancers and 5,600 cases of cardiovascular diseases had been documented as of October, 2007. Lifestyle factors that were assessed in the baseline questionnaire were examined in relation to the subsequent risk of cancer and other lifestyle-related diseases. A significant inverse association between physical activity and the risk of colorectal cancer, particularly colon cancer, was observed in men ⁽¹⁵⁶⁾. Low intake of vitamin B6 was associated with increased risk of colorectal cancer in men, particularly in heavy drinkers ⁽¹⁵⁷⁾. Coffee consumption was inversely associated with the risk of invasive colon cancer in women ⁽¹⁵⁸⁾. Undergoing colorectal cancer screening was associated with a reduction in mortality from colorectal cancer ⁽¹⁵⁹⁾. A history of diabetes and current smoking were associated with increased risk of pancreatic cancer in men. Neither a higher body mass index (BMI) nor more leisure-time physical activity increased the risk of pancreatic cancer in either men or women ⁽¹⁶⁰⁾. Neither coffee nor green tea consumption increased the risk of pancreatic cancer ⁽¹⁶¹⁾. Height, weight and BMI were associated with an increased risk of breast cancer among postmenopausal women ⁽¹⁶²⁾. Early age at menarche for premenopausal women, late age at natural menopause, nulliparity and low parity for both pre-and post-menopausal women, and late age at first birth for postmenopausal women were significantly associated with an increased risk of breast cancer ⁽¹⁶³⁾. Isoflavone intake was associated with a decreased risk of localized prostate cancer. ^{(164, 165)}. For both non-flushers and flushers, there was a significant inverse association between alcohol consumption and the risk of acute myocardial infraction in men ⁽¹⁶⁶⁾. Dietary intake of isoflavones was associated with a reduced risk of cerebral and myocardial infraction in women, especially in postmenopausal women ⁽¹⁶⁷⁾. Dietary vitamin C reduced the risk of age-related cataracts ⁽¹⁶⁸⁾.

Two nested case-control studies using cryopreserved blood samples were performed. A significant association of plasma C-peptide with colorectal cancer, particularly colon cancer, was observed in men ⁽¹⁶⁹⁾. Plasma 25(OH)D in the lowest quartile was associated with an elevated risk of rectal cancer as compared with the combined category of the other quartiles ⁽¹⁷⁰⁾.

To develop an evidence-based cancer prevention strategy in terms of lifestyle intervention suitable for the Japanese population, a systematic literature review project and some interventional studies are in progress. The association between alcohol drinking and the cancer risk of each of total ⁽¹⁷¹⁾, lung ⁽¹⁷²⁾, breast ⁽¹⁷³⁾ cancer was evaluated.

A randomized controlled trial to assess the effectiveness of vitamin C supplementation for individuals with chronic atrophic gastritis to prevent gastric cancer in the high-risk area of Hiraka, Akita prefecture, has been 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 between 1998-2000, and the follow-up survey was completed in 2003. The collected data are under analysis.

The ethnic differences in the incidence of cancer 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. A case-control study for breast cancer has been completed and data analysis is in progress. A case-control study for colonic adenoma is in progress.

A project to evaluate risk of endocrine- disrupting chemicals (EDC) on human health is also in progress. A cross-sectional study among Japanese women consulting doctors for infertility suggests that those with higher serum organochlorine levels are at a lower risk of advanced endometriosis, and the association was modified by cytochrome P450 gene polymorphisms. ⁽¹⁷⁴⁾. In addition, those with higher urinary isoflavone levels were also at a lower risk of advanced endometriosis, which was modified by estrogen receptor 2 gene polymorphisms ⁽¹⁷⁵⁾. On the other hand, urinary bisphenol-A levels were not associated with the risk of endometriosis ⁽¹⁷⁶⁾.

A case-only study based on the Lung Cancer Database Project at the National Cancer Center Hospital East showed that female patients, especially for adenocarcinoma, were more likely to have a family history of breast cancer in first-degree relatives than male patients ⁽¹⁷⁷⁾. In a case-control study of 505 lung cancer patients and 256 noncancer controls, a significant association was noted between alcohol consumption and lung cancer risk, which was modified by ALDH2 gene polymorphisms ⁽¹⁷⁸⁾. A case-control study of colorectal cancer patients and health check-up controls showed no association between H. pylori infection or gastrin level with the risk of colorectal cancer. However, serologically determined atrophic gastritis was associated with an increased risk for rectal cancer ⁽¹⁷⁹⁾. A case-control study of stomach cancer patients and health check-up controls showed the possibility that the E-cadherin (CDH1) haplotypes may be associated with the risk of gastric cancer ⁽¹⁸⁰⁾. The assessment of heterocyclic amine (HCA) intake based on the levels of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in the hair indicated that HCA intake as estimated from a food frequency questionnaire (FFQ) provides a reasonable ranking of individuals and that the FFQ is adaptable to large-scale epidemiological studies ⁽¹⁸¹⁾. Two reviews on the epidemiologic evidence for dietary factors and gastric or gastrointestinal cancers have been published ^{(182, 183)}. Specialized assistance was given for analysis of the clinical data. ⁽¹⁸⁴⁾.