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.

Association between variations in the fat mass and obesity-associated gene and pancreatic cancer risk: a case-control study in Japan.

BACKGROUND: It is clear that genetic variations in the fat mass and obesity-associated (FTO) gene affect body mass index and the risk of obesity. Given the mounting evidence showing a positive association between obesity and pancreatic cancer, this study aimed to investigate the relation between variants in the FTO gene, obesity and pancreatic cancer risk. METHODS: We conducted a hospital-based case-control study in Japan to investigate whether genetic variations in the FTO gene were associated with pancreatic cancer risk. We genotyped rs9939609 in the FTO gene of 360 cases and 400 control subjects. An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between rs9939609 and pancreatic cancer risk. RESULTS: The minor allele frequency of rs9939609 was 0.18 among control subjects. BMI was not associated with pancreatic cancer risk. Compared with individuals with the common homozygous TT genotype, those with the heterozygous TA genotype and the minor homozygous AA genotype had a 48% (OR=1.48; 95%CI: 1.07-2.04), and 66% increased risk (OR=1.66; 95%CI: 0.70-3.90), respectively, of pancreatic cancer after adjustment for sex, age, body mass index, cigarette smoking and history of diabetes. The per-allele OR was 1.41 (95%CI: 1.07-1.85). There were no significant interactions between TA/AA genotypes and body mass index. CONCLUSIONS: Our findings indicate that rs9939609 in the FTO gene is associated with pancreatic cancer risk in Japanese subjects, possibly through a mechanism that is independent of obesity. Further investigation and replication of our results is required in other independent samples.

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.

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.

Effect of coffee consumption on all-cause and total cancer mortality: findings from the JACC study.

Coffee consumption is known to be related to various health conditions. Recently, its antioxidant effects have been suggested to be associated with all-cause or cancer mortality by various cohort studies. However, there has been only one small Asian cohort study that has assessed this association. Thus, we tried to assess the association of coffee with all-cause and total cancer mortality by conducting a large-scale cohort study in Japan. A total of 97,753 Japanese men and women aged 40-79 years were followed for 16 years. Hazard ratios and 95% confidence intervals of all-cause and total cancer mortality in relation to coffee consumption were calculated from proportional-hazards regression models. A total of 19,532 deaths occurred during the follow-up period; 34.8% of these deaths were caused by cancer. The all-cause mortality risk decreased with increasing coffee consumption in both men and women, with a risk elevation at the highest coffee consumption level (≥4 cups/day) compared with the 2nd highest consumption level in women, although the number of subjects evaluated at this level was small. No association was found between coffee consumption and total cancer mortality among men, whereas a weak inverse association was found among women. The present cohort study among the Japanese population suggested that there are beneficial effects of coffee on all-cause mortality among both men and women. Furthermore, the results showed that coffee consumption might not be associated with an increased risk of total cancer mortality.

An overview of genetic polymorphisms and pancreatic cancer risk in molecular epidemiologic studies.

BACKGROUND: Although pancreatic cancer has been extensively studied, few risk factors have been identified, and no validated biomarkers or screening tools exist for early detection in asymptomatic individuals. We present a broad overview of molecular epidemiologic studies that have addressed the relationship between pancreatic cancer risk and genetic polymorphisms in several candidate genes and suggest avenues for future research. METHODS: A comprehensive literature search was performed using the PubMed database. RESULTS: Overall, individual polymorphisms did not seem to confer great susceptibility to pancreatic cancer; however, interactions of polymorphisms in carcinogen-metabolizing genes, DNA repair genes, and folate-metabolizing genes with smoking, diet, and obesity were shown in some studies. The major problem with these studies is that, due to small sample sizes, they lack sufficient statistical power to explore gene-gene or gene-environment interactions. Another important challenge is that the measurement of environmental influence needs to be improved to better define gene-environment interaction. It is noteworthy that 2 recent genome-wide association studies of pancreatic cancer have reported that variants in ABO blood type and in 3 other chromosomal regions are associated with risk for this cancer, thus providing new insight into pancreatic cancer etiology. CONCLUSIONS: As is the case in other complex diseases, common, low-risk variants in different genes may act collectively to confer susceptibility to pancreatic cancer in individuals with repeated environmental exposures, such as smoking and red meat intake. Clarification of gene-gene and gene-environmental interaction is therefore indispensable for future studies. To address these issues, a rigorously designed molecular epidemiologic study with a large sample is desirable.

Number of children and all-cause mortality risk: results from the Japan Collaborative Cohort Study.

BACKGROUND: The mean total birth rate of the world had been gradually decreasing, with the rate in Japan now at its lowest level internationally. From a public health perspective, it is important to determine the impact of the number of children on all-cause mortality. METHODS: A total of 96,311 individuals from the Japan Collaborative Cohort Study were followed from 1988-90 for an average of 14.4 years. Hazard ratios (HRs) with a 95% confidence interval were calculated from proportional hazard models to estimate the risk of all-cause mortality according to the number of children. RESULTS: As of 2006, a total of 18,807 deaths had occurred. Both childless men and women showed higher all-cause mortality risks than those with two children (HR: 1.17 in men and 1.29 in women). Those with one child also showed higher risks (1.13 and 1.16, respectively). Having four or more children among men and five or more children among women also posed a risk (1.16 in men with four children and 1.22 in women with five or more children), showing a U-shaped association between the number of children and all-cause mortality risk. The risk of having only one child seemed evident with the decrease in age among both men and women, while the risk of having many children was apparent with the increase in age. CONCLUSION: We found a U-shaped association between the number of children and all-cause mortality among both men and women, with the lowest risk among those with two children.

Relationship of sFas with metabolic risk factors and their clusters.

BACKGROUND: Metabolic risk factors are known to cause atherosclerosis through inflammation. In the process of inflammation, soluble Fas (sFas) may interfere with the apoptotic pathway and contribute to dysregulated inflammation. Recent studies suggest sFas as a marker of inflammation in patients with cardiovascular diseases. However, whether a relationship exists between sFas levels and metabolic risk factors among healthy subjects remains unclear. MATERIALS AND METHODS: We measured the serum sFas levels of 876 subjects selected as controls for a nested case-control study within the JACC Study. The adjusted means of the sFas levels were compared according to the presence of overweight/obesity, hypertension, hyperlipidaemia, diabetes and their clusters. RESULTS: sFas level was significantly associated with overweight/obesity (2.42 ng mL(-1) in overweight/obese men and 2.19 in others) and hyperlipidaemia (2.34 ng mL(-1) in men with hyperlipidaemia and 2.19 in others) among men, though not with hypertension or diabetes. Moreover, a clear association between sFas levels and the cluster number of metabolic risk factors was observed independently with age, smoking and drinking(2.39, 2.28, 2.24 and 2.11 ng dL(-1) in men with three to four, two, one and none of the four metabolic risk factors respectively). However, among women, clear associations were not observed between sFas levels and the four metabolic risk factors or their clustering. CONCLUSIONS: Serum sFas levels appear to be associated with overweight/obesity, hyperlipidaemia and clusters of metabolic risk factors among men, suggesting that sFas may elevate to down-regulate increased apoptosis in atherogenesis processes.

Impact of smoking and other lifestyle factors on life expectancy among japanese: findings from the Japan Collaborative Cohort (JACC) Study.

BACKGROUND: A number of lifestyle factors, including smoking and drinking, are known to be independently associated with all-cause mortality. However, it might be more effective in motivating the public to adopt a healthier lifestyle if the combined effect of several lifestyle factors on all-cause mortality could be demonstrated in a straightforward manner. METHODS: We examined the combined effects of 6 healthy lifestyle behaviors on all-cause mortality by estimating life expectancies at 40 and 60 years of age among 62 106 participants in a prospective cohort study with a 14.5-year follow-up. The healthy behaviors selected were current nonsmoking, not heavily drinking, walking 1 hour or more per day, sleeping 6.5 to 7.4 hours per day, eating green leafy vegetables almost daily, and having a BMI between 18.5 to 24.9. RESULTS: At age 40, we found a 10.3-year increase in life expectancy for men and a 8.3-year increase for women who had all 6 healthy behaviors, as compared with those who had only 0 to 2 healthy behaviors. Increases of 9.6 and 8.2 years were observed for men and women, respectively, at age 60 with all 6 healthy behaviors. When comparing currently nonsmoking individuals with 0 to 1 healthy behaviors, the life expectancy of smokers was shorter in both men and women, even if they maintained all 5 other healthy behaviors. CONCLUSIONS: Among individuals aged 40 and 60 years, maintaining all 6 healthy lifestyle factors was associated with longer life expectancy. Smokers should be encouraged to quit smoking first and then to maintain or adopt the other 5 lifestyle factors.

Healthy lifestyle and preventable death: findings from the Japan Collaborative Cohort (JACC) Study.

OBJECTIVE: To evaluate the effect of baseline combination of 6 lifestyle factors on all-cause mortality. METHODS: A total of 62,106 Japanese men and women aged 40-79 years were followed for 12.5 years on average. Hazard ratios and 95% confidence intervals (CIs) of all-cause mortality in relation to healthy lifestyle factors (not currently smoking, not heavily drinking, walking 1 h or more per day, sleeping 6.5 to 7.4 h per day, eating green-leafy vegetables almost daily and BMI between 18.5 and 24.9) were calculated from proportional-hazards regression models. We also estimated population-attributable fractions of death to address the impact of potential lifestyle modifications on mortality. RESULTS: Until 2003, 8497 deaths were observed. Age-adjusted HR of all-cause mortality for the group with 6 healthy lifestyle factors was 0.42 (95% CI: 0.32-0.56) among men and 0.49 (0.39-0.60) among women, respectively, compared with the group with 0-2 healthy lifestyle factors. Even at ages 60-79 years, a healthy lifestyle has a major impact on mortality. Had the subjects achieved even a 1-point increment in their lifestyle scores, death rates of 24.7% among men and 18.5% among women could have been reduced. CONCLUSION: We found an inverse association between baseline combination of 6 healthy lifestyle factors and all-cause mortality as well as its impact on preventable fraction of death. Our results also demonstrated that healthy lifestyle behaviors are important even in old age.

Cigarette smoking and serum soluble Fas levels: Findings from the JACC study.

Cigarette smoking enhances low-grade systemic inflammation in the lung and other organs. Activated immune cells play an important role at early and late stages of inflammation, and in recent years, soluble Fas (sFas), an isoform of death molecule Fas, was found to interfere with the apoptotic pathways of these activated immune cells. The aim of this study was to confirm the association between cigarette smoking and sFas levels in healthy male subjects. We measured serum sFas levels of 4415 male subjects selected as controls for a nested case-control study within the large-scale cohort study conducted in Japan, called the JACC Study. Smoking status at baseline was evaluated by a self-administered questionnaire. Least square means of sFas according to smoking status and numbers of cigarettes smoked per day among smokers were calculated and adjusted for possible confounding factors. Mean sFas levels showed an increasing trend across never smokers, past smokers and current smokers, as 2.21 (95% CI: 2.14-2.27) ng/ml, 2.29 (2.22-2.36) ng/ml, and 2.36 (2.30-2.43) ng/ml, respectively. However, no dose-response relationship was observed between the number of cigarettes smoked per day and sFas levels among smokers.

Soluble Fas level and cancer mortality: findings from a nested case-control study within a large-scale prospective study.

Soluble Fas (sFas) is known to play an important role in the development of cancers of various sites. To confirm whether or not the serum sFas level can be a predictor of cancer, we conducted a nested case-control study within a large-scale population-based cohort study in Japan. Serum samples were collected from 39,242 participants (13,839 men and 25,403 women) at baseline, all of whom were followed until 1997 for mortality and until 1994 for cancer incidence. Three controls were randomly selected and matched to each cancer case for gender, age and residential area. Serum values of sFas were measured by enzyme-linked immuno-adsorbent assay, using commercially available kits. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using conditional logistic models, based on 798 total cancer mortality cases and their 2,353 matched controls. The risk of total cancer mortality was increased according to sFas levels, and the OR of the highest quartile compared with that of the lowest was 1.81 (95% CI; 1.40-2.34) after adjusting for smoking and drinking status, and body mass index. This positive association remained unaltered when cases were divided into 2 groups according to the observation period. Our results suggest that serum sFas has a possibility to detect people at high risk for cancer prior to diagnosis, since it increased before cancer diagnosis in those apparently healthy people.

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.

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.

Alcohol consumption and mortality among middle-aged and elderly Japanese men and women.

PURPOSE: We conducted a prospective cohort study to examine the association between alcohol intake and the risk of all-cause mortality among middle-aged and elderly Japanese men and women. METHODS: At baseline (1988-1990), a total of 110,792 Japanese men and women aged 40 to 79 years were asked to complete a questionnaire that included information on alcohol intake, and were followed up for all-cause mortality through December 31, 1999. Relative risks (95% confidence interval) were calculated using Cox proportional-hazards models. RESULTS: The risk of all-cause mortality was lowest among current drinkers with an alcohol intake of 0.1 to 22.9 g/d (RR, 0.80; 95% CI, 0.72-0.88 for men; and RR, 0.88; 95% CI, 0.77-1.00 for women). Excessive mortality associated with heavy drinking (> or = 69 g/d) was observed for cancer, cardiovascular disease and injuries and other external causes in men, while significantly reduced mortality with light drinking was seen for cancer in men and CVD in women. For men, the benefit associated with light alcohol consumption (< 23 g/d) was more apparent among nonsmokers than among smokers. CONCLUSION: Our prospective data show a 12% to 20% decreased risk of all-cause mortality in both Japanese men and women who consumed less than 23 g/d of alcohol (approximately 2 drinks), although heavy drinking increased that risk.

Diagnostic accuracy of serological kits for Helicobacter pylori infection with the same assay system but different antigens in a Japanese patient population.

Helicobacter pylori infection is thought to be a causal risk factor for gastric carcinoma. Recently, diagnostic accuracy of serological kits for H. pylori infection that were made in Western countries has been reported to be lower when used among Oriental populations. Diagnostic accuracy of two serological kits [HM-CAP and HM-CAP with antigens extracted from clinically isolated Japanese H. pylori strains (J-HM-CAP)] was investigated in 440 samples from a Japanese patient population by using the (13)C-urea breath test as gold standard. According to the original optimal cut-off value, HM-CAP provided 87.5 % sensitivity and 84.8 % specificity with 86.8 % accuracy and J-HM-CAP provided 95.5 % sensitivity and 81.9 % specificity with 92.3 % accuracy. This study suggests that antigens from HM-CAP are satisfactory for examining a Japanese patient population, but that using local antigens improves accuracy.

Lack of associations between genetic polymorphisms in GSTM1, GSTT1 and GSTP1 and pancreatic cancer risk: a multi-institutional case-control study in Japan.

BACKGROUND: We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. MATERIALS AND METHODS: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. The study population consisted of 360 patients and 400 control subjects, who were recruited from several medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk. RESULTS: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 and GSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) for individuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1- present genotypes. No synergistic effects of smoking or GST genotypes were observed. CONCLUSIONS: Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study.

Multilocus sequence typing of DNA from faecal specimens for the analysis of intra-familial transmission of Helicobacter pylori.

This study used multilocus sequence typing (MLST) of total DNA extracted from faecal specimens to genotype Helicobacter pylori to analyse intra-familial transmission. Faecal DNA was extracted and amplified by nested PCR. The products were analysed by direct sequencing and the allele type was determined using an MLST website. Mother-to-child transmission was suspected in at least two of three families, and father-to-child transmission was suspected in one family.

BMI and all-cause mortality among Japanese older adults: findings from the Japan collaborative cohort study.

The association between BMI and all-cause mortality may vary with gender, age, and ethnic groups. However, few prospective cohort studies have reported the relationship in older Asian populations. We evaluated the association between BMI and all-cause mortality in a cohort comprised 26,747 Japanese subjects aged 65-79 years at baseline (1988-1990). The study participants were followed for an average of 11.2 years. Proportional-hazards regression models were used to estimate mortality hazard ratios (HRs) and 95% confidence intervals. Until 2003, 9,256 deaths occurred. The underweight group was associated with a statistically higher risk of all-cause mortality compared with the mid-normal-range group (BMI: 20.0-22.9); resulting in a 1.78-fold (95% confidence interval: 1.45-2.20) and 2.55-fold (2.13-3.05) increase in mortality risk among severest thin men and women (BMI: <16.0), respectively. Even within the normal-range group, the lower normal-range group (BMI: 18.5-19.9) showed a statistically elevated risk. In contrast, being neither overweight (BMI: 25.0-29.9) nor obese (BMI: > or =30.0) elevated the risk among men; however among women, HR was slightly elevated in the obese group but not in the overweight group compared with the mid-normal-range group. Among Japanese older adults, a low BMI was associated with increased risk of all-cause mortality, even among those with a lower normal BMI range. The wide range of BMI between 20.0 and 29.9 in both older men and women showed the lowest all-cause mortality risk.

Variations in serum transforming growth factor-beta1 levels with gender, age and lifestyle factors of healthy Japanese adults.

Elevated serum or plasma Transforming Growth Factor-beta1 (TGF-beta1) {levels have been} linked to cancer and other diseases in numerous studies; however, very few studies have reported an association between circulating TGF-beta1 and lifestyle factors in healthy people. We examined the association between serum TGF-beta1 levels and gender, age, body mass index (BMI), smoking, and drinking in a large population-based cohort study (N =9,142). Serum TGF-beta1 levels were {detected by the Quantikine enzyme-linked immunoassay kit (R&D Systems). The data indicated highly significant (p< ;0.0001) difference in serum TGF-beta1 levels between men (mean value: 37.6 +/- 0.12 ng/mL, N=4888) and women (mean value: 35.1 +/- 0.12 ng/ml, N=4254)}. Serum TGF-beta1 levels decreased with age (trend p< 0.0001) and were positively associated with obesity (trend p< 0.0001) in both men and women. We observed a significant trend with increased serum TGF-beta1 levels corresponding to increased amount of tobacco and alcohol consumption in men (trend p< 0.0001). These findings suggest that serum TGF-beta1 levels appear to be modulated by {gender}, age and lifestyle factors such as obesity, cigarette smoking, and alcohol drinking in healthy Japanese adults.