MMH Khan et al Asian Pacific Journal of Cancer Prevention, Vol 7, 2006 260 Asian Pacific J Cancer Prev, 7, 260-266 RESEARCH COMMUNICATION Introduction Endometrial cancer (EC) accounted for 198,783 new cases (3.9% of all new cancer cases in women) worldwide in 2002, making this the 7th most common cancer in the world. Because of its favorable prognosis, the number of deaths from this disease was only one-fourth (50,327 deaths, 1.7% of all cancer deaths in women). It is therefore the 13th most common cause of female cancer death worldwide (Parkin et al., 2005). International data indicate that this disease is more prominent in developed than developing countries. Among the developed countries, the incidence rate is relatively low in Japan as compared to the countries of north America and Europe (Parkin et al., 2005; Persson and Adami, 2002; IARC, 2002). International variation in diets, body size, body fat distribution, and exogenous estrogen use may contribute to the observed global differences in the incidence of these hormone-dependent malignancies. For Risk of Endometrial Cancer Mortality by Ever-use of Sex Hormones and Other Factors in Japan MMH Khan 1 *, Mitsuru Mori 1 , Fumio Sakauchi 1 , Khandoker Aklimunnessa 1 , Tatsuhiko Kubo 2 , Yoshihisa Fujino 2 , Sadao Suzuki 4 , Shinkan Tokudome 4 , Akiko Tamakoshi 5 for the JACC Study Group 1 Department of Public Health, Sapporo Medical University School of Medicine; 2 Department of Clinical Epidemiology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health; 3 Fukuoka Institute of Occupational Health, Fukuoka; 4 Department of Health Promotion and Preventive Medicine, Nagoya City University Graduate School of Medical Sciences; 5 Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Japan. Email: khan@sapmed.ac.jp or mmhkhan70@yahoo.com Abstract 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. Key Words: Endometrial cancer mortality - cohort study - ever use of sex hormones - hormone replacement therapy - Japan instance, lower prevalence of hormone replacement therapy (HRT) in Japanese community as compared to other countries such as United States (Nagata et al., 1996), and consumption of plant based cuisines which are low in fat and high in fiber that typify the Japanese diets may be some of the reasons of the lower incidence of EC in Japan (Goodman et al., 1997). Although incidence rates are still low in Japan, several reports (IARC, 2002; Persson and Adami, 2002; IARC 1997; IARC, 1987) have indicated that EC has been increasing gradually over the last few decades. Increasing availability of estrogen to the estrogen sensitive endometrium may increase the risk of EC (Parslov et al., 2000). In Japan, the production of conjugated estrogen, often used for HRT, has increased 2-fold between 1992 and 1993. Pharmaceuticals companies and women’s magazines are actively advertising the importance of HRT especially for menopause women (Nagata et al., 1996). Increased life expectancy, a reduction