Roles and causes of abnormal DNA methylation in gastrointestinal cancers.

Evidence now suggests that epigenetic abnormalities, particularly altered DNA methylation, play a crucial role in the development and progression of human gastrointestinal malignancies. Two distinct DNA methylation abnormalities are observed together in cancer. One is an overall genome-wide reduction in DNA methylation (global hypomethylation) and the other is regional hypermethylation within the CpG islands of specific gene promoters. Global hypomethylation is believed to induce proto-oncogene activation and chromosomal instability, whereas regional hypermethylation is strongly associated with transcriptional silencing of tumor suppressor genes. To date, genes involved in regulation of the cell cycle, DNA repair, growth signaling, angiogenesis, and apoptosis, are all known to be inactivated by hypermethylation. Recently developed techniques for detecting changes in DNA methylation have dramatically enhanced our understanding of the patterns of methylation that occur as cancers progress. One of the key contributors to aberrant methylation is aging, but other patterns of methylation are cancer-specific and detected only in a subset of tumors exhibiting the CpG island methylator phenotype (CIMP). Although the cause of altered patterns of DNA methylation in cancer remains unknown, it is believed that epidemiological factors, notably dietary folate intake, might strongly influence DNA methylation patterns. Recent studies further suggest that polymorphisms of genes involved in folate metabolism are causally related to the development of cancer. Identifying epidemiological factors responsible for epigenetic changes should provide clues for cancer prevention in the future.

A case-control study of multiple myeloma in Japan: association with occupational factors.

Recently the incidence rate of multiple myeloma (MM) has increased in Japan. Epidemiologic efforts have suggested that certain occupational and chemical exposures are likely to increase the risk for MM. We therefore performed a case-control study of MM, examining occupational factors. Data for 57 cases and 57 controls were obtained from Sapporo Medical University Hospital and its affiliated hospitals in Hokkaido. Controls were matched to each case by gender, age (+/- 5 years) and hospital. Detailed information regarding several factors possibly related to MM was obtained by interviews in hospitals. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated with adjustment for cigarette smoking as confounding factor. The occupational category of agriculture and fishery showed a significant association with increased risk (OR = 5.89, 95% CI = 1.24-28.04). Occupational exposure to chemical products including organic solvents or petroleum showed a significant association with increased risk (OR = 8.05, 95% CI = 1.01-64.45). Medical histories of operation for appendicitis and blood transfusion were associated with decreased risk, but not significantly. Our results suggested that occupational exposure to chemicals might play a role in the risk of MM.

Dietary habits and cancer mortality among middle aged and older Japanese living in hokkaido, Japan by cancer site and sex.

Dietary factors are thought to be closely associated with the development of human cancers and hence numerous studies in this area have already been conducted in the United States and other Western countries. Comparatively few prospective studies have been published in Japan, especially for Hokkaido people. The present investigation was therefore performed to assess links between four leading cancers and some of the Japanese common dietary factors through a cohort study (1984-2002) in Hokkaido by analyzing 1,524 men and 1,634 women separately aged 40 and over. Adjusted Cox proportional hazard regression was used to calculate the relative risk (RR) for each dietary factor. For men, two dietary factors, miso soup (RR=0.2, 95% confidence interval (95%CI)=0.1-0.8) and pickled vegetables (RR=0.2, 95%CI=0.1-0.8) were associated with lower risk for stomach and colorectal cancer respectively. For women, three factors, namely salty confectionary (RR=3.5, 95%CI=1.1-10.9), black tea (RR=3.8, 95%CI=1.1-13.6), and carbonated drink/juice (RR=3.9, 95% CI=1.4-11.1) appeared related to an elevated risk of stomach cancer. However, further analysis simultaneously with all other adjusted factors indicated only carbonated drink/juice (RR=3.1, 95%CI=1.1-8.9) to present a significant risk factor for stomach cancer. One factor, namely wild edible plants (RR=3.3, 95%CI=1.1-9.8), increased the risk for colorectal cancer in women. None of the dietary components were significantly associated with lung or pancreatic cancers. This study also indicated a wide variation in the impact of dietary factors by sex and cancer site, in line with earlier work, pointing to a necessity for careful interpretation. Further epidemiological investigations by sex with more study subjects and confounding factors will be useful for determining the contribution of individual dietary factors to development of human cancers in Hokkaido, Japan.

Higher consumption of green tea may enhance equol production.

BACKGROUND: Our previous case-control study revealed that Japanese living in Japan and Koreans living in Korea can be divided into equol producers who have an ability to metabolize daidzein to equol and non-producers, and that the incidence of prostate cancer is higher in the latter group. In the present study, we examined relationships between type of food intake and the capacity for equol production in Japanese subjects. METHODS: The subjects were the individuals analyzed for the ability to produce equol in our previous study and newly registered cases. From December 2000 to December 2002, 276 hospitalized patients were interviewed face-to-face and blood samples were collected before breakfast. These included 122 patients with prostate cancer and 154 age-matched controls. RESULTS: The frequency of equol producers (0.5 ng/ml or more) among cases and controls was 29% and 45%, respectively (p = 0.004). The consumption of soybeans and green tea were significantly higher in equol producers than in the non-producers (p<0.05). By contrast, the consumption of selenium and fiber was significantly lower in equol producers (p<0.05). CONCLUSIONS: Our results suggest that higher consumption of soybean and green tea are strongly related to the establishment of a capacity for equol production.

Magnitude of arsenic toxicity in tube-well drinking water in Bangladesh and its adverse effects on human health including cancer: evidence from a review of the literature.

Only after a decade from 1993, arsenic contamination of groundwater in Bangladesh has been reported as the biggest arsenic catastrophe in the world. It is a burning public health issue in this country. More than 50 percent of the total population is estimated at risk of contamination. Already thousands of people have been affected by the disease arsenicosis. Many more may be on the way to manifest lesions in future. We conducted a review of previous studies and published articles including MEDLINE database on this issue. We found that 59 districts out of 64 have been already affected by arsenic in underground drinking water, where this particular source of drinking water is the main source for 97 percent of the rural people. The water is unfortunately now a great threat for the human being due to high level of arsenic. Continuous arsenic exposure can lead people to develop arsenicosis, which in turn elevates the risk of cancer. Skin lesions are the most common manifestations in arsenicosis patients. Relatively poor rural people and other socio-economically disadvantaged groups are more affected by this exposure. Until now cancer patients have been relatively limited in Bangladesh. One of the reasons may be that several years are needed to show cancer manifestations from the beginning of arsenic exposure. But it is suspected that after some years a large number of patients will appear with cancer in different sites for arsenic exposure in drinking water. Various studies have been conducted in arsenic affected countries - notably in Argentina, Chile, China, Japan, and Taiwan -to find the potential of arsenic exposure to cause development of cancer. Among the arsenic related cancers, liver, lung, skin, bladder and kidney cancers are reported to be prevalent in these countries. Unfortunately no scientific study has been yet conducted in Bangladesh to find the relationship between arsenic exposure and cancers in different sites of the body. So our aim is to conduct an ecological as well as a case-control study in the country in the future.