Randomized controlled trials suggest that protein restriction may retard the progression of CKD toward ESRD. However, the effects of dietary protein intake level and the food sources of dietary protein on the risk of ESRD in the general population remain unclear. We investigated these effects in the Singapore Chinese Health Study, a prospective population-based cohort that recruited 63,257 Chinese adults aged 45-74 years from 1993 to 1998. We collected habitual diet information via a validated semiquantitative food frequency questionnaire and identified ESRD via record linkage with a nationwide registry. In all, 951 cases of ESRD occurred over a mean follow-up of 15.5 years. Regarding total protein intake, compared with the lowest quartile, the three higher quartiles combined had a hazard ratio for ESRD of 1.24 (95% confidence interval [95% CI], 1.05 to 1.46), but the dose-dependent association across the quartiles was not statistically significant (P trend =0.16). Red meat intake strongly associated with ESRD risk in a dosedependent manner (hazard ratio for highest quartile versus lowest quartile,1.40 [95% CI, 1.15 to 1.71; P trend ,0.001]). Intake of poultry, fish, eggs, or dairy products did not associate with risk of ESRD. In substitution analysis, replacing one serving of red meat with other food sources of protein associated with a maximum relative risk reduction of 62.4% (95% CI, 33.1 to 78.9; P,0.01). Our study shows that red meat intake may increase the risk of ESRD in the general population and substituting alternative sources of protein may reduce the incidence of ESRD.

Background:The increasing prevalence of diabetes may contribute to the rising incidence of hepatocellular carcinoma (HCC) in the US and other developed countries where HCC incidence is relatively low. Data from prospective studies on diabetes and risk of HCC in at-risk populations due to high prevalence of viral hepatitis in southeast Asia are sparse.Methods:The Singapore Chinese Health Study is a prospective cohort of 63 257 middle-aged and older Chinese men and women enrolled in 1993–1998. Besides an in-person interview administered to all participants at baseline, testing of serologic markers of hepatitis B or C infections were performed on a subset of cohort subjects. After a mean follow-up of 14 years, 499 cohort participants developed HCC.Results:A history of diabetes at baseline was associated with a hazard ratio of 2.14 (95% confidence interval, 1.69–2.71). This statistically significant association was comparable in magnitude between men and women, and remained equally strong across strata of subjects defined by the number of years between their first clinical diagnosis of diabetes and time of enrolment in this cohort. Within a nested case-control set of cohort subjects tested for serological markers of hepatitis B or C infections, the diabetes–HCC association was found to be present mainly among those devoid of any markers.Conclusion:A history of diabetes at baseline is highly associated with non-viral HCC. Future studies are warranted to elucidate the biological mechanism underpinning the role of diabetes in nonviral-related hepatocarcinogenesis.

BackgroundWe investigated the association of living alone with mortality among older persons, independently of marital, health and other factors, and explored its effect modification by age group, sex, marital status and physical functional disability.MethodUsing data from 8 years of mortality follow up (1 September 2003 to 31 December 2011) of 2553 participants in the Singapore Longitudinal Ageing Studies (SLAS) cohort, we estimated hazard ratio (HR) of mortality associated with living alone using Cox proportional hazard models.ResultsAt baseline, 7.4 % (N = 189) of the participants were living alone, and 227 (8.9 %) died during the follow up period. Living alone was significantly associated with mortality 1.66 (95 % CI, 1.05–2.63), controlling for health status (hypertension, diabetes, chronic lung disease, stroke, heart disease, kidney failure, IADL–ADL disability and depressive symptoms), marital status and other variables (age, sex, housing type). Possible substantive effect modification by sex (p for interaction = 0.106) and marital status (p for interaction <0.115) were observed: higher among men (HR = 2.36, 95 % CI, 1.24–4.49) than women (HR = 1.14, 95 % CI, 0.58–2.22), and among single, divorce or widowed (HR = 2.26, 95 % CI, 1.24–4.10) than married individuals (HR = 0.83, 95 % CI, 0.30–2.31).ConclusionLiving alone was associated with increased mortality, independently of marital, health and other variables. The impact of living alone on mortality appeared to be stronger among men and those who were single, divorced or married.

ObjectivesThe relationship between body mass index (BMI) with mortality risk, in particular the BMI category associated with the lowest all-cause and CVD-and-stroke mortality and the BMI threshold for defining overweight or obesity in older persons is controversial. This study investigated the age-dependent associations of BMI categories with all-cause and cardiovascular disease (CVD) and stroke mortality.MethodProspective cohort study (Singapore Longitudinal Ageing Studies) of older adults aged 55 and above, followed up from 2003 to 2011. Participants were 2605 Chinese with baseline BMI and other variables. Outcome Measurement: Mortality hazard ratios (HR) for all-cause and CVD and stroke mortality.ResultsOverall, BMI showed a U-shaped relationship with all-cause and CVD and stroke mortality, being lowest at Normal Weight-II category (BMI 23.0–24.9 kg/m2). Most evidently among the middle-aged (55–64 years), all-cause mortality risks relative to Normal Weight-II were elevated for underweight (30.0; HR = 4.05,p = 0.0423). Among the old (≥65 years), however, Overweight and Obese categories were not significantly associated with increased all-cause mortality (HR from 0.98 to 1.29), but Overweight-Obese was associated with increased CVD and stroke mortality (HR = 10.0, p = 0.0086).ConclusionBMI showed a U-shaped relationship with mortality. Among older persons aged 65 and above, the overweight-or-obese category of BMI was not associated with excess all-cause mortality.

Cytochrome P450 2A6 (CYP2A6) catalyzes the metabolism of nicotine and the tobacco-specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Genetic variation in CYP2A6 may affect smoking behavior and contribute to lung cancer risk. A nested case-control study of 197 lung cancer cases and 197 matched controls was conducted within a prospective cohort of 63 257 Chinese men and women in Singapore. Quantified were five genetic variants of CYP2A6 (*1A, *4, *7, *9 and *12) and urinary metabolites of nicotine [total nicotine, total cotinine, total trans-3'-hydroxycotinine (3HC)] and NNK (total NNAL, free NNAL, NNAL-glucuronide, NNAL-N-glucuronide, and NNAL-O-glucuronide). Higher urinary metabolites of nicotine and NNK were significantly associated with a 2- to 3-fold increased risk of lung cancer after adjustment for smoking intensity and duration. Lower CYP2A6-determined nicotine metabolizer status was significantly associated with a lower ratio of total 3HC over total cotinine, lower total nicotine equivalent and reduced risk of developing lung cancer (all Ptrend < 0.001). Compared with normal metabolizers, odds ratios (95% confidence intervals) of developing lung cancer for intermediate, slow and poor metabolizers determined by CYP2A6 genotypes were 0.85 (0.41-1.77), 0.55 (0.28-1.08) and 0.32 (0.15-0.70), respectively, after adjustment for smoking intensity and duration and urinary total nicotine equivalents. Thus the reduced risk of lung cancer in smokers with lower CYP2A6 activity may be explained by lower consumption of cigarettes, less intense smoking and reduced CYP2A6-catalyzed activation of the tobacco-specific lung carcinogen NNK.