Development and Validation of a Novel Score to Predict Mortality in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: CRISTEN.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, severe mucocutaneous adverse reactions. Severity prediction at early onset is urgently required for treatment. However, previous prediction scores have been based on data of blood tests. OBJECTIVE: This study aimed to present a novel score that predicts mortality in patients with SJS/TEN in the early stages based on only clinical information. METHODS: We retrospectively evaluated 382 patients with SJS/TEN in a development study. A clinical risk score for TEN (CRISTEN) was created according to the association of potential risk factors with death. We calculated the sum of these risk factors using CRISTEN, and this was validated in a multinational survey of 416 patients and was compared with previous scoring systems. RESULTS: The significant risk factors for death in SJS/TEN comprised 10 items, including patients' age of ≥65 years, ≥10% body surface area involvement, the use of antibiotics as culprit drugs, the use of systemic corticosteroid therapy before the onset, and mucosal damage affecting the ocular, buccal, and genital mucosa. Renal impairment, diabetes, cardiovascular disease, malignant neoplasm, and bacterial infection were included as underlying diseases. The CRISTEN model showed good discrimination (area under the curve [AUC] = 0.884) and calibration. In the validation study, the AUC was 0.827, which was statistically comparable to those of previous systems. CONCLUSION: A scoring system based on only clinical information was developed to predict mortality in SJS/TEN and was validated in an independent multinational study. CRISTEN may predict individual survival probabilities and direct the management and therapy of patients with SJS/TEN.

Associations between cigarette smoking and biliary tract cancer by anatomic subsite and sex: a prospective cohort study in Japan.

PURPOSE: Biliary tract cancer (BTC) has not been considered a tobacco-related cancer, largely because of inconclusive results from epidemiological studies. We herein evaluate the association between cigarette smoking and risk of death from BTC by anatomic subsite and sex using data from a large, prospective cohort study in Japan. METHODS: The present study included 97,030 Japanese individuals who were enrolled in 1988-1990 and followed until 31 December 2009. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the association of BTC with cigarette smoking, including smoking status, number of cigarettes smoked per day, and pack-years of smoking. RESULTS: During a mean follow-up of 16.2 years, we documented 484 deaths (187 from gallbladder cancers and 297 from cancers of other and unspecified biliary tract parts). After adjustment for sex, age, body mass index, alcohol consumption, and history of gallstones, current smokers had a higher risk of death due to BTC (RR = 1.35, 95% CI = 1.01-1.79) than never smokers. In the analyses by anatomic subsite, current smoking was associated with an increased risk of death from gallbladder cancer (RR = 1.89 95% CI = 1.19-3.02), whereas no evidence of an association was noted for cancers of other and unspecified biliary tract parts (RR = 1.10, 95% CI = 0.77-1.58). Moreover, mortality risk increased with an increasing number of cigarettes smoked per day and pack-years of smoking, particularly for gallbladder cancer in men. CONCLUSION: Cigarette smoking is associated with an increased risk of death from BTC, particularly gallbladder cancer, in Japanese men.

The nationwide epidemiological survey of Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan, 2016-2018.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs). The first national epidemiological survey of SJS/TEN was carried out in 2008. We conducted a new survey to identify changes from the previous survey. OBJECTIVE: The present survey aimed to estimate the number of SJS/TEN patients in Japan between 2016 and 2018 (primary survey) and to clarify clinical epidemiological profiles (secondary survey). METHODS: A primary survey asking for numbers of SJS/TEN patients during the study period was sent to 1205 institutions nationwide. A secondary survey was sent to institutions reporting SJS/TEN patients, seeking detailed information. RESULTS: Yearly prevalence per million was 2.5 for SJS and 1 for TEN. The secondary survey allowed analysis of 315 SJS cases and 174 TEN cases from 160 institutions. Mean age was 53.9 years in SJS, and 61.8 years in TEN. Mortality rate was 4.1 % for SJS and 29.9 % for TEN. In TEN, mean age and mortality rates had increased from the previous survey. The ratio of expected to observed mortality calculated by SCORTEN score was lowest with high-dose steroid therapy (0.40), followed by steroid pulse therapy (0.52). CONCLUSION: The present findings suggest that the mortality rate of TEN has increased because of increases in mean ages of patients and patients with malignant neoplasm as underlying disease. When comparing the ratio of expected mortality to actual mortality, high-dose steroid therapy achieved the greatest reduction in mortality.

Association between shift work and the risk of death from biliary tract cancer in Japanese men.

BACKGROUND: There is increasing evidence suggesting that shift work involving night work may increase cancer risk. METHODS: We examined the association between working rotating shifts and the risk of death from biliary tract cancer among Japanese men who participated in the Japan Collaborative Cohort Study. Of the 46,395 men recruited, 22,224 men aged 40-65 at baseline (1988-1990) who reported working full-time or were self-employed were included in the present analysis. The study subjects were followed through December 31, 2009. Information regarding occupation and lifestyle factors was collected using a self-administered questionnaire. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for the risk of death from biliary tract cancer in relation to shift work. RESULTS: During a mean 17-year follow-up, we observed 94 biliary tract cancer deaths, including 23 deaths from gallbladder cancer and 71 deaths from extrahepatic bile duct cancer. Overall, shift work was associated with a statistically non-significant increase in the risk of biliary tract cancer, with an HR of 1.50 (95 % CI: 0.81-2.77), among rotating shift workers. When the analysis was limited to extrahepatic bile duct cancer, a significant association appeared, with a multivariable-adjusted HR of 1.93 (95 % CI: 1.00-3.72) for rotating shift workers. CONCLUSION: Our data indicate that shift work may be associated with increased risk of death from extrahepatic bile duct cancer in this cohort of Japanese men. The association with gallbladder cancer remains unclear because of the small number of deaths.

Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR).

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction caused by specific drug. It is characterized by visceral organ involvement and reactivation of various human herpesviruses. Although sporadic reports have documented certain conditions that appear after the resolution of DIHS/DRESS, little information is available on sequelae after resolution of DIHS/DRESS in a large patient population. The Asian Research Committee on Severe Cutaneous Adverse Reactions, comprised of doctors from Japan and Taiwan, conducted a survey on sequelae and deterioration of the underlying disease in patients with DIHS/DRESS. This was achieved by directly interviewing patients who had been followed-up by experts or through a questionnaire mailed to patients. Questions were asked about new onset cardiovascular disease, collagen disease or autoimmune disease, gastrointestinal disease, renal disease, respiratory disease, neoplasms, and other diseases such as herpes zoster and diabetes mellitus, as well as deterioration of the underlying disease. A total of 145 patients were analyzed in this study. The following newly developed diseases after recovery from DIHS/DRESS were observed: Graves' disease (n = 2), Hashimoto's disease (n = 3), painless thyroiditis (n = 2), fulminant type 1 diabetes mellitus (n = 5), and infectious diseases (n = 7). Several DIHS/DRESS patients with pre-existing renal dysfunction required lifelong hemodialysis. DIHS/DRESS is a condition that increases the risk of new onset of disease. Long-term observation of DIHS/DRESS can provide an opportunity to investigate substantial diseases from onset to the full-blown stage. Patients with DIHS/DRESS require careful long-term follow-up.

Active and passive smoking and risk of death from pancreatic cancer: findings from the Japan Collaborative Cohort Study.

BACKGROUND: There is uncertainty in the risk of pancreatic cancer with particular aspects of smoking, such as a dose-response relationship and cumulative amount, in Japanese men and women. Very few studies have addressed the role of passive smoking in pancreatic cancer among Japanese women. METHODS: We examined the association between active or passive smoking and the risk of death from pancreatic cancer using data from the Japan Collaborative Cohort Study. The cohort participants (46,395 men and 64,190 women) were followed-up for mortality from baseline (1988-1990) through December 31, 2009. Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). RESULTS: During follow-up, we recorded 611 pancreatic cancer deaths. After adjustment for potential confounding factors, current smokers had a significantly increased risk of death from pancreatic cancer compared with non-smokers, with an RR of 1.70 (95% CI: 1.33-2.19). The risk of death from pancreatic cancer significantly increased with increasing numbers of cigarettes smoked per day. Exposure to environmental tobacco smoke (ETS) in public spaces was not associated with risk of death from pancreatic cancer. The RR for women who reported ETS exposure was 1.20 (95% CI: 0.87-1.67). Women exposed to ETS during childhood or adolescence had 1.21-fold increased risk, but the association was statistically insignificant. CONCLUSIONS: Cigarette smoking is associated with an approximately 70% increase in the risk of death from pancreatic cancer. Further studies with improved exposure assessment are needed to better quantify the association between passive smoking and pancreatic cancer.

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.

A prospective cohort study of shift work and the risk of death from pancreatic cancer in Japanese men.

PURPOSE: There is mounting evidence that shift work involving night work increases cancer risk. We examined the relationship between working rotating shifts and the risk of death from pancreatic cancer on the basis of data from the Japanese Collaborative Cohort Study (JACC Study). METHODS: The present analysis was restricted to 22,224 men who were 40-65 years of age at baseline (1988-1990) and who reported working full time or were self-employed in the JACC Study. The subjects were followed through 31 December 2009. Information on occupation and lifestyle factors was collected using a self-administered questionnaire. The Cox proportional hazards model was used to estimate the relative risk (RR) and 95% confidence interval (CI) for the risk of death from pancreatic cancer in relation to shift work. RESULTS: During the follow-up period, 127 pancreatic cancer deaths were observed. Overall, we found no statistically significant increase in the risk of death from pancreatic cancer associated with rotating shift work. As compared to day-shift workers, the RRs were 0.83 (95% CI 0.43-1.60) for rotating shift workers and 0.61 (95% CI 0.22-1.60) for fixed night-shift workers, after adjustment for potential confounding factors. The multivariable-adjusted RR was 1.34 (95% CI 0.66-2.75) among rotating shift workers in the analysis restricted to men who reported working full time at baseline. CONCLUSIONS: Our data did not support the hypothesis that shift work is significantly associated with the risk of death from pancreatic cancer in this cohort of Japanese men.

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.

Current status of the treatment of microscopic polyangiitis and granulomatosis with polyangiitis in Japan.

BACKGROUND: This study aimed to describe the epidemiologic characteristics of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in Japan. METHODS: We used the database of the Ministry of Health, Labour and Welfare (MHLW) from 2006 to 2008, and analyzed data from 938 patients (MPA = 697, GPA = 241) who fulfilled the MHLW diagnostic criteria and had registered within a year after onset. RESULTS: The mean ages of the MPA and GPA patients were 69.4 ± 0.4 and 58.4 ± 1.1 years, respectively. Renal (86.9 %), chest (73.7 %), and nervous system (45.2 %) symptoms were common in MPA patients. Ear, nose, and throat (86.7 %), chest (78.0 %), and renal (60.6 %) symptoms were frequently observed in GPA patients. The concomitant use of cyclophosphamide (CY) with corticosteroids was observed in 22.2 % of the MPA patients and 58.5 % of the GPA patients. In multivariate analysis, the concomitant use of CY was associated with a younger age and pulmonary hemorrhage in MPA patients, and the avoidance of CY was associated with nervous system symptoms and rapidly progressive glomerulonephritis in GPA patients. Plasma exchanges were inducted in 5.2 % of the MPA patients and 4.1 % of the GPA patients. The addition of plasma exchange was associated with elevation of the serum creatinine level in patients with both MPA and GPA. CONCLUSION: A dominance of MPA and a reduced frequency of renal involvement in GPA patients may be significant features of the Japanese population. Clinical practice relating to MPA and GPA in Japan can be characterized as follows: CY is used less commonly, and plasma exchange is employed for patients with deteriorated renal function.

Reduced serum vascular endothelial growth factor receptor-2 (sVEGFR-2) and sVEGFR-1 levels in gastric cancer patients.

The relationship between gastric cancer and serum vascular endothelial growth factor receptor-1 (sVEGFR-1) and sVEGFR-2, which are soluble form receptor proteins of vascular endothelial growth factor (VEGF), has not been extensively studied. VEGF, sVEGFR-1 and sVEGFR-2 were measured in the sera obtained before surgical operation from 164 gastric cancer patients and from 164 healthy controls matched for age and gender. Compared with controls, the cases showed elevated VEGF (P < 0.01) and reduced sVEGFR-1 (P = 0.07) and sVEGFR-2 (P = 0.02). The difference in VEGF levels was small among men and when the outcome was early cancer. The difference in sVEGFR-1 levels was significant or borderline significant only in men and when the outcome was diffuse type cancer. The difference in sVEGFR-2 levels was significant only in men and when the outcome was advanced or diffuse type cancer. The sensitivities and specificities of VEGF, sVEGFR-1 and sVEGFR-2 were all approximately 60%. For diffuse type cancer, sVEGFR-2 showed a sensitivity of 62.4% and a specificity of 63.4%, which was similar to serum pepsinogen. In conclusion, elevated VEGF and reduced sVEGFR-1 and sVEGFR-2 in serum are characteristic of gastric cancer patients, and the value of serum sVEGFR-2 in the diagnosis of diffuse type gastric cancer should be further evaluated.

Lack of association between risk of biliary tract cancer and circulating IGF (Insulin-like Growth Factor) -I, IGF-II or IGFBP-3 (IGF-binding Protein-3): A nested case-control study in a large scale cohort study in Japan.

Biliary tract cancer, encompassing gallbladder and bile duct cancers, has a poor prognosis, but little is known of the etiology. A nested case-control study was here conducted to evaluate the association between serum levels of IGF-I, IGF-II and IGFBP-3 and death from biliary tract cancer. In a large scale cohort study, 35 gallbladder and 42 bile duct cancers were observed during the follow-up. For each subject in the case group, 1-3 control subjects (228 in total) were selected randomly, matched for sex, age (as near as possible) and residential area. The subjects were divided into tertiles by circulating levels of IGF-I, IGF-II or IGFBP-3. Using conditional logistic regression, risks among the tertiles were compared adjusted for defecation, smoking and drinking habits. No remarkable differences in risks of gallbladder or bile duct cancer were observed among tertiles of IGF-I or IGF-II, and no remarkable trend was observed. Circulating IGFBP-3 showed an inverse U-shape association with gallbladder cancer and a U-shaped one with bile duct cancer. Associations between IGF-I or IGF-II and gallbladder or bile duct cancer thus were lacking or very weak. The observed U- and inverse U-shaped association of IGFBP-3 with the cancers is not suggestive of any meaningful relationships.

Serum soluble fas levels and superoxide dismutase activity and the risk of death from pancreatic cancer: A nested case-control study within the Japanese Collaborative Cohort Study.

In a search for novel circulating biomarkers for pancreatic cancer, we examined the association between serum soluble Fas (sFas) levels and superoxide dismutase (SOD) activity and the risk of death from pancreatic cancer in a nested case-control study within the Japanese Collaborative Cohort Study. Case subjects were 68 persons who were free of morbidity, had provided a blood sample at baseline (1988-1990), and subsequently died from pancreatic cancer before December 31, 1997. Control subjects were 199 matched persons who were selected from the remaining participants in the cohort. Conditional logistic regression models were used to estimate age-adjusted and multivariate-adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). No statistically significant differences were noted in mean sFas levels (p=0.11) and SOD activity (p=0.42) between cases and controls. Overall, neither serum sFas levels nor SOD activity were associated with the risk of pancreatic cancer deaths, after adjustment for area, BMI, cigarette smoking, and history of diabetes. Furthermore, no significant risk trends were noted. Our results do not support the hypothesis that serum sFas levels and SOD activity are associated with pancreatic cancer risk.

Green tea consumption and the risk of pancreatic cancer in Japanese adults.

OBJECTIVE: Green tea polyphenols have been shown to inhibit tumor growth in animal and in vitro studies. We examined the relationship between green tea consumption and the risk of death from pancreatic cancer in a large Japanese cohort. METHODS: At baseline (1988-1990), study participants reported the frequency and amount of green tea consumption during the past year. They were followed-up for mortality until December 31, 2003. Relative risk and 95% confidence intervals were calculated from Cox proportional hazard models. RESULTS: During an average follow-up of 13 years, we observed 292 pancreatic cancer deaths. In men and women combined, the relative risk was 1.23 (95% confidence interval, 0.84-1.80) for participants who consumed 7 or more cups of green tea per day as compared with those who consumed less than 1 cup per day, after adjustment for potential confounding factors. No significant trend in risk reduction was noted, with increasing consumption of green tea. We found no inverse association between cups of green tea consumed per day and the risk of pancreatic cancer in either men or women. CONCLUSIONS: Our findings do not support the hypothesis that green tea consumption is associated with decreased risk of pancreatic cancer in humans.

Cigarette smoking, alcohol drinking and the risk of gallbladder cancer death: a prospective cohort study in Japan.

Gallbladder cancer is a rare cancer with a poor prognosis, and few risk factors have been identified to date. This prospective study was conducted to evaluate the association of cigarette smoking and alcohol consumption with the risk of gallbladder cancer death. A baseline survey in 45 areas throughout Japan was conducted from 1988 to 1990 using a self-administered questionnaire, and a total of 113,496 participants (65,740 women) aged 40-89 years at entry were followed for 15 years. During the follow-up period, 165 gallbladder cancer deaths (95 women) were observed. Among women, the hazard ratio (HR) [95 percent confidence interval: 95% CI] of current smoker was 2.00 [0.91-4.42], when adjusted for age and drinking. There was no clear association between alcohol consumption and the risk. Among men, HR of current smoker was 2.27 [1.05-4.90]. HRs of those who smoked 21 cigarettes or more per day and those with 801-1,000 cigarette-years were 3.18 [1.18-8.53] and 3.44 [1.40-8.45], respectively, and positive linear associations were observed between that risk and the number of cigarettes per day (p for trend = 0.007) or "cigarette-years" (p for trend = 0.012). The alcohol dose was linearly associated with risk (p for trend = 0.004), where the HR among those who consumed 72.0 g or more of alcohol per day was 3.60 [1.29-9.85]. Among both men and women, cigarette smoking may elevate the risk of death from gallbladder cancer. Drinking may pose an elevated risk among men, but that seems to be less true among women.

Obesity, physical activity and the risk of pancreatic cancer in a large Japanese cohort.

It is unclear whether body mass index (BMI) and physical activity are associated with the risk of pancreatic cancer in Asian populations. We examined these associations in the Japanese Collaborative Cohort Study for Evaluation of Cancer Risk. Our cohort study included 110,792 Japanese men and women at enrollment (1988-1990). Data on height, body weight (at baseline and at age 20 years) and physical activity were obtained from a questionnaire. Cox proportional hazards models were used to estimate the relative risks of pancreatic cancer mortality. We observed a total of 402 pancreatic cancer deaths during the follow-up period. Men with a BMI of 30 or more at age 20 years had a 3.5-fold greater risk compared with men with a normal BMI. Women with a BMI of 27.5-29.9 at baseline had approximately 60% increased risk compared with women with a BMI of 20.0-22.4. In men, weight loss of 5 kg or more between 20 years of age and baseline age was associated with an increased risk of pancreatic cancer death. In contrast, women with weight loss of 5 kg or more over the same period had a decreased risk. Physical activity was not associated with pancreatic cancer risk in either men or women. Obesity in young adulthood may be associated with an increased risk of death from pancreatic cancer in Japanese men. The risk of pancreatic cancer in relation to BMI seems to differ according to sex and the period over which BMI was measured.

Dietary habits and pancreatic cancer risk in a cohort of middle-aged and elderly Japanese.

Few epidemiological studies have examined associations between diet and pancreatic cancer in Japan. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, we evaluated the relationship between dietary factors, including meat, vegetable, and fruit intake, and the risk of pancreatic cancer deaths. Among the original cohort established between 1988 and 1990, 46,465 men and 64,327 women aged 40-79 yr were followed-up through December 31,1999. During 1,042,608 person-years of follow-up, we documented 300 deaths from pancreatic cancer. A 33-item food-frequency questionnaire was used to assess dietary intake at the baseline survey. Cox proportional-hazards models were used to estimate the relative risks of pancreatic cancer death in relation to the intake frequency of food items. We did not observe an overall association between meat intake and pancreatic cancer risk. Except for a 50% decrease in risk associated with high fruit intake among men, we did not find other significant inverse relationships between vegetable and fruit intake and pancreatic cancer risk. Smoking did not modify the associations with dietary habits. Our study suggested that high consumption of pickles and wild edible plants, mainly bracken, might be related to increased pancreatic cancer risk; however, this finding should be confirmed in other epidemiological studies.

Association of menstrual and reproductive factors with pancreatic cancer risk in women: findings of the Japan Collaborative Cohort Study for Evaluation of Cancer Risk.

BACKGROUND: The etiology of pancreatic cancer remains largely unknown. We examined the association of pancreatic cancer deaths with menstrual and reproductive factors in a cohort study involving Japanese women. METHODS: A total of 63,273 women were followed up for mortality from 1988 to 1999. Information on menstrual and reproductive factors was obtained by a questionnaire survey at baseline. Cox proportional-hazards models were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for death from pancreatic cancer in relation to menstrual and reproductive factors. RESULTS: During 631,401 person-years of follow-up, 154 women died from pancreatic cancer. Parity was not significantly associated with the risk of death from pancreatic cancer; the RR was 0.80 (95% CI, 0.31-2.11) for women with six or more births compared with women with zero or one birth. We found no significant overall association with other reproductive factors, including pregnancy, age at first birth, and menopause. The risk appeared to increase with increasing age at menarche; the RR was 1.49 (95% CI, 0.95-2.34) for women who had menarche after 16 years of age compared to those who had menarche before they were 15 years old. CONCLUSIONS: Our prospective data indicate that menstrual and reproductive factors are not associated with the risk of death from pancreatic cancer among Japanese women.

Highly salted food and mountain herbs elevate the risk for stomach cancer death in a rural area of Japan.

BACKGROUND: Although many case-control and experimental studies have shown that highly salted foods are risk factors for stomach cancer, only a few cohort studies have supported the relationship. METHODS: In a cohort study conducted in a rural area of Japan, 8035 residents aged over 30 years (approx. 55% were female) filled out a questionnaire. Seventy-six of them died from stomach cancer during an 11-year follow-up period. In the questionnaire, intake frequencies of 29 food items, smoking and drinking habits were investigated. Tsukemono (pickled vegetables) and tsukudani (foods deep boiled in soy sauce) are highly salted foods in the area. Frequency of each food item intake was classified into three levels, and age- and sex-adjusted risks were calculated using proportional hazard models. RESULTS: In the final model obtained by backward elimination, frequent intake of tsukemono and tsukudani and that of mountain herbs remained as significant risk factors. Compared with the least frequent intake, risk (95% confidence interval) of the most frequent intake was 5.4 (1.8-16.3) for highly salted foods (P for trend < 0.01) and 3.7 (1.4-9.6) for mountain herbs (P for trend = 0.04). CONCLUSION: Highly salted foods and mountain herbs were important risk factors for death from stomach cancer.

Serum transforming growth factor-beta1 levels and pancreatic cancer risk: a nested case-control study (Japan).

OBJECTIVE: To examine the relationship of baseline levels of serum TGF-beta1 to the subsequent risk of death from pancreatic cancer in a nested case-control study. METHODS: The cases were 85 persons who had provided a blood sample at baseline and subsequently died of pancreatic cancer during the study period. For each case, three controls were randomly selected from among the cohort participants, and were matched for each case by sex, age (+/-1 year), and study area. Serum TGF-beta1 levels were measured with enzyme-linked immunosorbent assay (ELISA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from conditional logistic models. RESULTS: The mean of serum TGF-beta1 levels was significantly higher among cases than among controls (p = 0.01). Individuals with serum TGF-beta1 levels in the highest quartile had a 2.5-fold increase in risk as compared with those in the lowest quartile (OR, 2.5; 95% CI, 0.9-6.9), after adjustment for month of blood draw, cigarette smoking, body mass index and history of diabetes. Excluding 12 pancreatic cancer deaths that occurred within three years of follow-up did not alter the positive association. CONCLUSION: Our prospective data indicate that high serum TGF-beta1 levels may be associated with an increased risk of death from pancreatic cancer.