Reproductive history and health screening for women and mortality in the Japan Collaborative Cohort Study for Evaluation of Cancer (JACC).

Reproductive history and participation in health screening for women were surveyed among female subjects, and interesting results were obtained in the present analyses. Women who had never experienced pregnancy had significantly increased risks of death from all causes and cerebrovascular disorders compared with those who had experienced 1 or 2 pregnancies. In contrast, women who had experienced 3 or 4 pregnancies had significantly decreased risks of death from all causes, all cancers, rectal cancer, and breast cancer. Among women who had ever undergone mass screening examination for uterine cervical cancer, there were significantly lower risks of death from all causes, all cancers, stomach cancer, uterine cervical cancer, urinary tract cancer, and ischemic heart diseases compared with those who had not had such experience.

Marital status and having children and mortality in the Japan Collaborative Cohort Study for Evaluation of Cancer (JACC).

Marital status has been identified as an important social factor associated with mortality. Interesting results were obtained in the present analyses of the Japan Collaborative Cohort Study. Death of spouse was positively associated with risks of male death from all causes, all cancers, and ischemic heart diseases, compared with married status. Divorce or separation was positively associated with risks from all causes among men and women, all cancers among women, and single status was also positively associated with risks from all causes among men and women, and ischemic heart diseases among men. Having large numbers of children was also found to be a risk factor.

Risk factors for multiple myeloma: evidence from the Japan Collaborative Cohort (JACC) study.

This study assessed the association of multiple myeloma (MM) with age, body mass index (BMI, kg/m(2)), physical activity, occupational history, and medical history for a Japanese cohort of 46,157 men and 63,541 women aged 40-79 years followed during 1988-2003 years. Cox proportional hazard model was mainly used to estimate the age and sex adjusted hazard ratio (HR) of MM including 95% confidence interval (CI) for both sexes. Same model, adjusted for age, was also used for each sex. In total, 98 MM deaths (men=49 and women=49) was observed for both sexes. Higher age groups (60-69 and 70-79 years) experienced significantly higher unadjusted HR of MM than the age group of 40-49 years. Men revealed significantly higher age-adjusted MM than women (HR=1.5; 95% CI=1.0-2.2). For both sexes, higher BMI of >or=30 kg/m(2)) (HR=2.8; 95% CI=1.0-7.7), walking <or=30 minutes/day (HR=2.0; 95% CI=1.2-3.4), worried about personal relationship in working place (HR=2.3; 95% CI=1.3-4.2), restricted own pace in working place (HR=1.9; 95% CI=1.0-3.4), and history of peptic ulcer (HR=1.7; 95% CI=1.0-2.7) significantly increased age and sex adjusted MM risk. Some of the above-mentioned significant associations became insignificant for age adjusted sex specific analyses. However, these findings should be validated by further epidemiologic studies in Japan before generalization.

Site-specific cancer risk due to diabetes mellitus history: evidence from the Japan Collaborative Cohort (JACC) Study.

The study examined the association of diabetes mellitus (DM) history with total and common site-specific cancers using a large cohort of 23,378 men and 33,503 women, extracted from 127,477 healthy participants of the JACC Study who were aged 40-79 years and living in 24 municipalities in Japan. At enrollment during 1988-90, each subject completed a self-administered questionnaire including items for age, sex, body mass index (BMI), smoking, drinking, past history of DM and cancer. Adjusting for age, BMI, smoking, and drinking in the Cox's proportional hazard model, incidence rate ratios (IRR) with 95% confidence intervals (95%CIs) were estimated for both sexes. During the follow-up period, total cancers and site-specific cancers were identified. A history of DM was reported by 7.5% of men and 4.6% of women. DM significantly increased the risk of liver cancer for both men (IRR=2.30; 95%CI=1.47-3.59) and women (IRR=2.70; 95%CI=1.20-6.05). Significant increased and reduced risk due to DM for men were also found for non-Hodgkin lymphoma (IRR=2.77; 95%CI=1.04-7.38) and stomach cancer (IRR=0.67; 95%CI=0.46-0.99) respectively. For females, a reduced risk of stomach cancer due to DM (IRR=0.49; 95%CI=0.23-1.04) was also revealed. Since a history of DM here demonstrated significant associations with some site-specific cancers, their relationships should be studied further in Japan for validation.

Risk of endometrial cancer mortality by ever-use of sex hormones and other factors in Japan.

OBJECTIVES: To examine associations of ever-use of sex hormones (EUSH) and other factors with endometrial cancer (EC) mortality through a nation-wide Japan Collaborative Cohort Study. METHODS: A total of 63,541 women aged 40-79 years, enrolled in 1988-90 from 45 municipalities of Japan, were followed until 2003 to record their vital status. Using baseline data, the Cox proportional hazard model (age adjusted and multivariate) was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for EC mortality by selected factors, including EUSH. Bivariate analysis was also conducted to establish associations between EUSH and other factors. RESULTS: The mortality rate from EC was 2.6 per 100,000 person-years during the mean follow-up period of 13.3 years. Prevalence rate of EUSH was 5.2%. Significantly increased risk of EC mortality was found for EUSH with both age adjusted (HR=6.43, 95%CI=2.10-19.67) and multivariate (HR=5.33; 95%CI=1.51-18.82) analyses. Bivariate analysis indicated that history of diabetes mellitus, smoking, drinking, and age at first delivery were positively associated with EUSH, whereas age, number of delivery, number of pregnancy, and age at menarche demonstrated inverse links. CONCLUSIONS: Our results imply that EUSH may increase the risk of EC mortality among Japanese women. However, further studies with more deaths are needed to validate the results.

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.

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.

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.