Body mass index and weight change during adulthood are associated with increased mortality from liver cancer: the JACC Study.

BACKGROUND: We investigated the association of baseline body mass index (BMI) and weight change since age 20 years with liver cancer mortality among Japanese. METHODS: The data were obtained from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). A total of 31 018 Japanese men and 41 455 Japanese women aged 40 to 79 years who had no history of cancer were followed from 1988 through 2009. RESULTS: During a median 19-year follow-up, 527 deaths from liver cancer (338 men, 189 women) were documented. There was no association between baseline BMI and liver cancer mortality among men or men with history of liver disease. Men without history of liver disease had multivariable hazard ratios (HR) of 1.95 (95%CI, 1.07-3.54) for BMI less than 18.5 kg/m(2) and 1.65 (1.05-2.60) for BMI of 25 kg/m(2) or higher, as compared with a BMI of 21.0 to 22.9 kg/m(2). BMI was positively associated with liver cancer mortality among women and women with history of liver disease. Weight change since age 20 years was positively associated with liver cancer mortality among women regardless of history of liver disease. Women with history of liver disease had a multivariable HRs of 1.96 (1.05-3.66) for weight gain of 5.0 to 9.9 kg and 2.31 (1.18-4.49) for weight gain of 10 kg or more, as compared with weight change of -4.9 to 4.9 kg. CONCLUSIONS: Both underweight (BMI <18.5 kg/m(2)) and overweight (BMI ≥25 kg/m(2)) among men without history of liver disease, and weight gain after age 20 (weight change ≥5 kg) among women with history of liver disease, were associated with increased mortality from liver cancer.

Cohort profile of the Japan Collaborative Cohort Study at final follow-up.

The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was established in the late 1980s to evaluate the risk impact of lifestyle factors and levels of serum components on human health. During the 20-year follow-up period, the results of the study have been published in almost 200 original articles in peer-reviewed English-language journals. However, continued follow-up of the study subjects became difficult because of the retirements of principal researchers, city mergers throughout Japan in the year 2000, and reduced funding. Thus, we decided to terminate the JACC Study follow-up at the end of 2009. As a final point of interest, we reviewed the population registry information of survivors. A total of 207 (0.19%) subjects were ineligible, leaving 110 585 eligible participants (46 395 men and 64 190 women). Moreover, errors in coding date of birth and sex were found in 356 (0.32%) and 59 (0.05%) cases, respectively, during routine follow-up and final review. Although such errors were unexpected, their impact is believed to be negligible because of the small numbers relative to the large total study population. Here, we describe the final cohort profile at the end of the JACC Study along with selected characteristics of the participants and their status at the final follow-up. Although follow-up of the JACC Study participants is finished, we will continue to analyze and publish study results.

Obesity/weight gain and breast cancer risk: findings from the Japan collaborative cohort study for the evaluation of cancer risk.

BACKGROUND: We analyzed data from the Japan Collaborative Cohort Study (36 164 women aged 40-79 years at baseline in 1988-1990 with no previous diagnosis of breast cancer and available information on weight and height) to examine the association between baseline body mass index (BMI)/weight gain from age 20 years and breast cancer risk in a non-Western population. METHODS: The participants were followed prospectively from enrollment until 1999-2003 (median follow-up: 12.3 years). During follow-up, breast cancer incidence was mainly confirmed through record linkage to population-based cancer registries. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% CIs for the association between breast cancer risk and body size. RESULTS: In 397 644.1 person-years of follow-up, we identified 234 breast cancer cases. Among postmenopausal women, the adjusted HR increased with BMI, with a significant linear trend (P < 0.0001). Risk was significantly increased among women with a BMI of 24 or higher (HR: 1.50, 95% CI: 1.09-2.08 for BMI of 24-28.9, and 2.13, 1.09-4.16 for BMI ≥ 29) as compared with women with a BMI of 20 to 23.9. Weight gain after age 20 years and consequent overweight/obesity were combined risk factors for postmenopausal breast cancer risk. This combined effect was stronger among women aged 60 years or older. However, the HRs were not significant in premenopausal women. CONCLUSIONS: Our findings support the hypothesis that weight gain and consequent overweight/obesity are combined risk factors for breast cancer among postmenopausal women, particularly those aged 60 years or older.

Relationship of hobby activities with mortality and frailty among community-dwelling elderly adults: results of a follow-up study in Japan.

BACKGROUND: The proportion of Japanese adults aged 65 years or older is predicted to increase; thus, it is becoming more important to identify factors that influence health status among elderly adults in Japan. We conducted a follow-up study of community-dwelling elderly adults to assess the relationship of hobby activities with mortality and incident frailty. METHODS: We randomly selected 3583 individuals aged 65 to 84 years from the residential registries of 7 study areas in Hokkaido, Japan in August 2007. Among them, 1955 (54.6%) returned completed questionnaires with written informed consent by mail. The baseline assessment questionnaire comprised questions on current and past involvement in hobby activities, self-perceived health status, smoking and drinking habits, and body height and weight. Questions on hobby activities were from 4 categories: solitary physical, group physical, solitary cultural, and group cultural activities. We later conducted a follow-up survey of the participants to ascertain all-cause mortality and incident frailty. A Cox proportional hazards model was used for analysis of data from September 2007 to May 2010. RESULTS: After adjusting for potential confounders, the risk of incident frailty among respondents participating in solitary physical activities was significantly lower than in those who did not participate in such activities (hazard ratio = 0.57; 95% CI 0.33, 0.99). Furthermore, the risk of incident frailty among respondents taking part in group cultural activities was significantly lower than in those who did not participate in such activities (0.41; 0.19, 0.87). CONCLUSIONS: These findings may be important for programs that seek to promote good health among elderly adults.

Relationship of serum superoxide dismutase activity and lifestyle in healthy Japanese adults.

Superoxide dismutase (SOD) is an antioxidant enzyme that acts to degrade superoxide, a major causitive factor for oxidative stress associated with cancer, cardiovascular disease, and various other ailments. Here, to assess an association between antioxidants and lifestyle factors related to cancer risk, we analyzed serum SOD activity among the subjects within a large-scale cohort study in Japan. As results, significant differences in serum SOD activity were found between the sexes (lower in males), among female age groups (lower in younger individuals), and in males with the BMI (lower in those with a high BMI). Linear increase in serum SOD activity with aging and decrease with BMI were observed in females. Significantly low SOD activity was evident in male heavy smokers. In contrast, elevation was noted in female frequent drinkers. In conclusion, our findings do suggest associations between serum SOD activity and lifestyle factors. However, for further study, establishment of a standard measurement method for SOD activity should be a high priority.

Serum insulin-like growth factors I and II, insulin-like growth factor binding protein-3 and risk of breast cancer in the Japan Collaborative Cohort study.

The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was planned in the late 1980s as a large-scale cohort study of persons in various areas of Japan. In the present study, we conducted a nested case-control study and examined associations of breast cancer risk with serum levels of insulin-like growth factors I and II (IGF-I, IGF-II), as well as insulin-like growth factor binding protein-3 (IGFBP-3), among women who participated in the JACC Study and donated blood at the baseline. Sixty-three women who died or suffered from breast cancer were examined. Two or three controls were selected to match each case for age at recruitment and the study area. Controls were alive and not diagnosed as having breast cancer at the diagnosis date of the cases. Associations between the serum IGF-I, IGF-II, IGFBP-3 and breast cancer risk were evaluated using a conditional logistic regression model. In premenopausal Japanese women, IGF-I showed a marginal negative dose-dependent association with the breast cancer risk (trend P= 0.08), but any link disappeared on taking into account IGFBP-3 (trend P= 0.47), which was likely to be inversely associated with the risk. In postmenopausal women, IGFBP-3 showed a marginal dose-dependent association with the risk (trend P= 0.06). Further studies are needed to confirm these findings.

Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: A nested case-control study in large scale cohort study in Japan.

High levels of insulin-like growth factor (IGF)-I are reported to be associated with an increased risk of prostate cancer. On the other hand, the insulin-like growth factor binding protein-3 (IGFBP-3) may decrease the risk. We therefore investigated the influence of serum IGF-I and IGFBP-3 on prostate cancer risk in a case-control study nested within a large-scale cohort in Japan (the Japan Collaborative Cohort Study). Information on lifestyle and sera of the subjects were collected in 1988-90. Serum IGF-I, IGF-II and IGFBP-3 were measured in sera stored at -80 degrees C by immuno-radiometric assay. In 13,508 male subjects of the cohort who donated sera, 40 cases and 120 controls (1:3 matched with age and survey area) were identified. Ages of the cases ranged from 59 to 79 years, with a mean of 69.8. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the highest and middle tertiles compared with the lowest in controls using a conditional logistic model. Non-adjusted ORs for the highest tertiles were 0.99 (95% CI, 0.34-2.91) for IGF-I (trend-P = 0.60), 1.91 (95% CI, 0.68-5.38) for IGFBP-3 (trend-P = 0.23), 1.73 (95% CI, 0.69-3.47) for IGF-II (trend-P = 0.23), and 0.67 (95% CI, 0.26-1.76) for the IGF-I/IGBP-3 ratio (trend-P = 0.83). Serum levels of IGF-I, IGF-II, IGFBP-3, or IGF-I/IGFBP-3 ratio were thus not thought to be associated with risk of prostate cancer.

Traditional Japanese diet and prostate cancer.

The traditional Japanese diet has been suggested by some researchers to be associated with a decreased risk of prostate cancer (PCa). In this paper, we assumed the following three characteristics of the traditional Japanese diet high in soybean products, high in fish, and low in red meat. Isoflavones, polyunsaturated long chain (n - 3) fatty acids, and saturated fatty acids were thought to be micronutrients in biological etiology relevant to soybean products, fish, and red meat, respectively. Analytical epidemiological studies on the risk of PCa were identified using the MEDLINE database from 1998 to 2007. Some published studies showed a negative association of soybean products and isoflavones to PCa risk, an inverse association for fish or polyunsaturated long chain (n - 3) fatty acids such as eicosapentaenic acid (EPA) and docosahexaenoic acid (DHA) with PCa risk, and a positive association of red meat or saturated fatty acids with PCa risk, respectively. In conclusion, although it is possible that the traditional Japanese diet may reduce the risk of PCa through a combination of characteristics such as being high in soybean products, high in fish, and low in red meat, further well-designed epidemiological studies such as nested case-control studies with nutritional analyses of blood samples are needed to confirm this association.

Effect of physical activity on breast cancer risk: findings of the Japan collaborative cohort study.

PURPOSE: This study aimed to examine prospectively the association between physical activity and breast cancer risk in a non-Western population. METHODS: We analyzed data from the Japan Collaborative Cohort Study, which included 30,157 women, ages 40 to 69 years at baseline (1988-1990), who reported no previous history of breast cancer, and provided information on their walking and exercise habits. The subjects were followed prospectively from enrollment until 2001 (median follow-up period, 12.4 years). Breast cancer incidence during this period was confirmed using records held at population-based cancer registries. The Cox proportional hazards model was used to estimate the hazard ratio (HR) for the association of breast cancer incidence with physical activity. RESULTS: During the 340,055 person-years of follow-up, we identified 207 incident cases of breast cancer. The most physically active group (who walked for > or = 1 hour per day and exercised for > or = 1 hour per week) had a lower risk of breast cancer (HR, 0.45; 95% confidence interval, 0.25-0.78) compared with the least active group after adjusting for potential confounding factors. The inverse association of exercise on breast cancer was stronger among those who walked for > or = 1 hour per day than those who walked for <1 hour per day (P = 0.042). These results were not significantly modified by menopausal status or body mass index (BMI). CONCLUSIONS: Our analysis provided evidence that physical activity decreased the risk of breast cancer. Walking for 1 hour per day and undertaking additional weekly exercise both seemed to be protective against breast cancer, regardless of menopausal status or BMI.

A prospective study of educational background and breast cancer among Japanese women.

OBJECTIVE: This prospective cohort study examined the association between educational level and breast cancer incidence in Japan. METHOD: A baseline survey was conducted between 1988 and 1990 among 110,792 residents of 45 areas, aged 40-79 years. Data were restricted to 24 areas where incidence registry data were available, and to subjects which provided information on educational level (32,646). The subjects were assigned to three groups according to their level of education (<16, 16-18, 18<). During 13 years of follow-up (328,931 person-year), 169 cases of breast cancer were newly diagnosed. RESULTS: Women with a high level of education had an increased risk of breast cancer (HR = 1.93, 95 percent confidence interval (95% CI): 1.18, 3.16, in women with the highest educational level) compared with women with the lowest educational level. Adjustment for lifestyle and reproductive factors did not substantially change the results. In addition, when analyses were stratified by age subgroups, the educational difference in breast cancer incidence was more evident among the younger than the elder subgroup. CONCLUSION: The present results suggested that cancer prevention strategies should recognize women with a higher educational level as a high risk group for breast cancer.

Comparison of the clinical features of Japanese patients with primary biliary cirrhosis in 1999 and 2004: utilization of clinical data when patients applied to receive public financial aid.

BACKGROUND: In Asia there are few reports considering time intervals in the examination of clinical features of primary biliary cirrhosis (PBC). Therefore, we tried to compare the characteristics of patients with PBC in two different years. METHODS: In two fiscal years (1999 and 2004), 9,761 and 13,142 patients with symptomatic PBC were registered to receive public financial aid from the Ministry of Health, Labour and Welfare of Japan, respectively. For the present study, clinical data from 2,127 patients in 1999 and 6,423 ones in 2004 were available. We compared the data in the two different years, including sex, age, major symptoms, and laboratory data. RESULTS: Male/female ratios were the same figure (0.13 for 1999 and 2004). The median age was significantly older in 2004 than in 1999 (59 years for 1999, 63 years for 2004, respectively, p<0.01). Jaundice and esophageal varices were found significantly less frequent in 2004 than in 1999 (p<0.01 for each item). Levels of total bilirubin,gamma-glutamyl transpeptidase (gamma-GTP), total cholesterol, and immunoglobulin M were significantly lower in 2004 than in 1999 (p< 0.02 for total bilirubin, and p<0.01 for other each item). The positive rate of antimitochondrial antibodies was significantly higher in 1999 than in 2004 (87.0% for 1999, 83.5% for 2004, respectively, p<0.01)). Complicated autoimmune diseases such as Sjögren's syndrome, rheumatoid arthritis, and chronic thyroiditis were found significantly more frequent in 2004 than in 1999 (p<0.01 for each item). CONCLUSIONS: Among the patients with PBC in 2004, an increase in median age, and lower levels of laboratory data such as gamma-GTP have been found compared to 1999. These results may show an accumulation of patients with better prognosis and the recent medical progress in controlling patients with PBC.J Epidemiol 2007; 17: 210-214.

Dietary habits and risk of ovarian cancer death in a large-scale cohort study (JACC study) in Japan.

The Japan Collaborative Cohort (JACC) Study was established in 1988-1990 and consisted of 46,465 men and 64,327 women observed until the end of 2003. A self-administered food frequency questionnaire was used as a baseline survey, and associations of dietary habits with the risk of ovarian cancer death were evaluated, taking into consideration age, menstrual and reproductive, anthropometric, and lifestyle factors. During the observation period, 77 women died of ovarian cancer. Hazard ratios for dietary factors were calculated by Cox's proportional hazards model. Being adjusted only for age, high intakes of dried or salted fish and Chinese cabbage were positively associated with the risk of ovarian cancer death, and the risk increased dose-dependently. In contrast, intake of soybean curd (tofu) was inversely associated with the risk. After being adjusted for age and potential confounding factors, the results regarding the intakes of dried or salted fish and Chinese cabbage did not change. However, the significance relating to the intake of soybean curd (tofu) was attenuated. From the results of this cohort study, it was suggested that high intakes of dried or salted fish and Chinese cabbage were potential risk factors of ovarian cancer death. In contrast, however, a high intake of soy bean curd (tofu) might have preventive effects against the risk.

Diabetes mellitus and kidney cancer risk: the results of Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study).

BACKGROUND: Diabetes mellitus (DM) is reported as being a risk factor associated with kidney cancer in Western countries. The incidence of both kidney cancer and DM is lower in Japan than the other developed countries, albeit on the rise. METHODS: We evaluated the risk factors for kidney cancer mortality using the database of the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC) study. The analytic cohort included 46 462 males and 64 326 females aged 40-79 years old. The Cox proportional hazards model was used to determine age- and sex-adjusted relative risk and its 95% confidence intervals. RESULTS: DM showed an increased, age- and sex-adjusted hazard ratio for kidney cancer mortality, but it failed to achieve statistical significance after controlling for other factors. CONCLUSION: The present study showed that DM increased the risk of kidney cancer death among the Japanese population. However, further studies may be needed to confirm the findings in the present study because DM failed to remain as a significant risk factor after controlling for other factors because of the small number of kidney cancer deaths in the present study.

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.

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.

Relationship between hepatocellular carcinoma and impaired glucose tolerance among Japanese.

BACKGROUND/AIMS: Both the incidence of diabetes mellitus (DM) and mortality from Hepatocellular carcinoma (HCC) are increasing in Japan. As the association of overall cancer and HCC with impaired glucose tolerance (IGT) has been studied rarely in the world including Japan, this study assessed their associations using cohort data of Hokkaido, Japan. METHODOLOGY: After getting ethical consent, this study included 908 men and 1,081 women aged 30-77 years during 1977-78 and collected detailed information using the baseline survey. The subjects were followed until 2002 and deaths were recorded using ICD-9. Classifying them into three groups of diabetes status namely DM, IGT, and normal, the relative risk (RR) of mortality was estimated by diabetes status using multivariate Cox model. RESULTS: This study revealed no association between overall cancer and diabetes status. However, the RR of mortality from HCC was about 11 times (HR= 10.8, 95%CI: 1.3-92.5) higher in IGT compared with normal group. DM group also showed higher risk of mortality than normal group. CONCLUSIONS: HCC mortality was significantly high among IGT group. However, as the results of the study were based on small data, further studies with large cohort are needed to address the association of IGT with overall cancer and HCC mortality in Japan.

Prospective cohort study of the risk of prostate cancer among rotating-shift workers: findings from the Japan collaborative cohort study.

Shift workers have been reported to have an increased risk of some cancers. However, the risk of prostate cancer in shift workers is not known to have been examined previously. This study prospectively examined the association between shift work and risk of prostate cancer incidence among 14,052 working men in Japan enrolled in a large-scale prospective cohort. A baseline survey was conducted between 1988 and 1990. Subjects were asked to indicate the most regular work schedule they had undertaken previously: day work, rotating-shift work, or fixed-night work. During 111,974 person-years, 31 cases of prostate cancer were recorded. The Cox proportional hazards model was used to estimate the risk, with adjustments for age, family history of prostate cancer, study area surveyed, body mass index, smoking, alcohol drinking, job type, physical activity at work, workplace, perceived stress, educational level, and marriage status. Compared with day workers, rotating-shift workers were significantly at risk for prostate cancer (relative risk = 3.0, 95% confidence interval: 1.2, 7.7), whereas fixed-night work was associated with a small and nonsignificant increase in risk. This report is the first known to reveal a significant relation between rotating-shift work and prostate cancer.

Effectiveness of cervical cancer screening over cervical cancer mortality among Japanese women.

BACKGROUND: Various studies have revealed that cervical cancer (CC) screening significantly reduces both CC incidence and mortality in developed countries. Although Japan introduced a nationwide government funded annual CC screening for the women aged 30+ in 1982, the effectiveness of CC screening on CC mortality has not yet been evaluated by any prospective cohort study. Therefore, the present study evaluated the association of CC mortality with self-reported CC screening and some other factors by a nationwide cohort study. METHODS: Baseline survey of the Japan Collaborative Cohort Study for the enrollment of subjects was completed during 1988-90 and followed until 2003. This study only analyzed 63,541 women, aged 30-79 years, who were free from any cancer history at enrollment. RESULTS: During the follow-up period, 38 CC deaths were identified. The mean age at mortality was 67.0 years, with a mortality rate of 4.2 per 100,000 person-years. Participation rate in CC screening was 46.9%. Age-adjusted Cox model indicated significantly lower CC mortality [hazard ratio (HR) = 0.30, 95% confidence interval (CI) = 0.12-0.74] due to CC screening. Protectiveness remained almost the same (HR = 0.30, 95% CI = 0.12-0.76) when adjusted for age, body mass index and number of deliveries. The results also revealed that CC screening could reduce at least 50% of CC deaths even after excluding the effect of possible self-selection bias. CONCLUSIONS: CC screening in Japan may reduce CC mortality significantly for women aged 30-79 years. However, further studies with more CC deaths and increased statistical power are needed to validate the findings.

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.

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.