Red Meat Intake and Risk of ESRD.

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 (Ptrend=0.16). Red meat intake strongly associated with ESRD risk in a dose-dependent manner (hazard ratio for highest quartile versus lowest quartile,1.40 [95% CI, 1.15 to 1.71; Ptrend<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.

Increased body mass index is a risk factor for end-stage renal disease in the Chinese Singapore population.

The relationship between body mass index (BMI) and end-stage renal disease (ESRD) is confounded by co-morbidities associated with both conditions. Furthermore, the association at low range BMI is controversial. We studied this association in the Singapore Chinese Health Study, a population-based prospective cohort that recruited Singaporean Chinese men and women 45-74 years of age from 1993 to 1998. Self-reported weight, height, lifestyle factors, usual diet, and medical history were collected via an interviewer-administered questionnaire. Incident ESRD cases were identified via record linkage with the nationwide ESRD registry. The computed Cox proportional hazard regression was adjusted for potential risk factors. After an average follow-up of 15.5 years, 827 incident ESRD cases were identified. Compared with a normal BMI of 18.5 to under 23 kg/m2, the hazard ratios and (95% confidence intervals) of ESRD risk for BMIs under 18.5, 23 to under 27.5, and 27.5 kg/m2 or more were 0.54 (0.37-0.79), 1.40 (1.20-1.64) and 2.13 (1.74-2.59), respectively. This significantly trended, linear, dose-dependent association was only present among those with no history of diabetes, hypertension, coronary heart disease, and stroke at baseline, but not significantly among those with any of these co-morbidities. Thus, BMI itself is a risk factor for ESRD in the general population and this association is present in those without pre-existing diabetes, hypertension, coronary heart disease, and stroke.

Timing of commencement of maintenance dialysis and mortality in young and older adults in Singapore.

BACKGROUND: The benefit of early dialysis initiation remains controversial with a paucity of data in Asians. Therefore, we undertook this study to investigate the association between timing of initiation of dialysis and mortality in Singapore. METHODS: The study used data from the Singapore Renal Registry database on 3286 patients with incident end-stage renal disease (ESRD) who commenced maintenance dialysis between January 2008 and December 2011. The data was further linked with the National Death Registry to acquire survival information until December 2013. We classified serum creatinine-based, estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at the start of dialysis into 3 categories: Early (≥10 ml/min/1.73m2), intermediate (5 to <10 ml/min/1.73m2) and late (<5 ml/min/1.73m2). RESULTS: In the unadjusted analysis, both early and intermediate dialysis initiation groups were at greater risk of death relative to late dialysis (Early: HR = 2.47; Intermediate: HR = 1.54). In the multivariate model, a significant interaction was detected between age and eGFR at dialysis initiation (p = 0.04). Adjusted mortality risk progressively increased with earlier initiation of dialysis for patients aged 18-54 years (p = 0.006) and aged 55 to 64 years (p < 0.001), and no statistically significant difference was observed for patients aged 65 years or older (p = 0.12). CONCLUSIONS: Early versus later initiation of dialysis was associated with significantly higher risk of mortality in Singapore's non-elderly population, and appeared to offer no survival advantage among the elderly.

Acute kidney injury increases the risk of end-stage renal disease after cardiac surgery in an Asian population: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is associated with increased morbidity and mortality. The long-term association between AKI and end-stage renal disease (ESRD) in an Asian population is unknown. Given the high prevalence of diabetes and a younger age of presentation for cardiac surgery, it is important to track this progression of kidney disease. Therefore, we studied the long-term risk of ESRD and mortality in our Asian patients who developed AKI after cardiac surgery. METHODS: With ethics approval, we prospectively recruited 3008 patients who underwent cardiac surgery in Singapore between 2008 and 2012, and followed them up till 2014. ESRD and mortality information were obtained from the Singapore Renal Registry and Singapore Registry of Births and Deaths respectively. AKI was defined using the Acute Kidney Injury Network (AKIN) criteria, and ESRD was defined as stage 5 chronic kidney disease requiring renal replacement therapy. The Cox proportional hazards regression model was used to analyze associations between AKI and the primary outcome of ESRD and the secondary outcome of death. RESULTS: The AKI incidence was 29.1%. During a mean follow-up of 4.4 ± 2.8 years, 0.9% developed ESRD. The hazard ratio (HR) for developing ESRD was 4.7 (95% C.I. = 1.736-12.603, p = 0.002) for AKIN stage 1 patients, and 5.8 (95% C.I. = 1.769-18.732, p = 0.004) for AKIN stage 2 and 3 patients; while the HR for mortality was 1.7 (95% C.I. = 1.165-2.571, p = 0.007) for AKIN stage 1 patients, and 2.5 (95% C.I. = 1.438-4.229, p < 0.001) for AKIN stage 2 and 3 patients. CONCLUSIONS: AKI is associated with ESRD and mortality after cardiac surgery in our Asian population. The trajectory from AKI to ESRD is rapid within 5 years of cardiac surgery. A concerted periodic follow-up assessment is advocated for AKI patients post-cardiac surgery.

30-year follow-up study of IgA nephritis in a Southeast Asian population: an evaluation of the Oxford histological classification
.

BACKGROUND: In 1985 we reported that 11% of a cohort of 151 patients with IgA nephritis (IgAN) had developed end-stage renal disease (ESRD) after a follow-up period of 5 years. 15 years later, 35% had developed ESRD. METHODS: We retrieved 125 stored renal biopsy paraffin blocks of the original cohort. From these, 102 patients were included in the present study and scored according to the Oxford classification as 21 specimens with less than 8 glomeruli were excluded and in 2 others, tissue samples were too tiny for a re-block. ESRD was ascertained by linking the study cohort to the Singapore Renal Registry at the National Registry of Diseases Office. RESULTS: Renal survival curves for each of the Oxford MEST lesions: endocapillary proliferation (E) (p < 0.04), segmental glomerulosclerosis (S) (p < 0.05), tubular atrophy/interstitial fibrosis (p < 0.0001) were significantly associated with ESRD. Mesangial hypercellularity, less commonly associated with progressive chronic kidney disease (CKD) in the study, was independently associated with ESRD at 30 years (p < 0.03). In this cohort, E and S were associated with lower eGFR at presentation and doubling of serum creatinine in the first 5 years. This study's initial 5 years was representative of the "natural history" of IgAN since no renin-angiotensin system (RAS) blockers or immunosuppression were administered. This represents the early phase of disease progression. E and S may be considered "early disease activity predictors". CONCLUSION: Mesangial hypercellularity and tubular atrophy/interstitial fibrosis (M1 and T1/T2 lesion) of the Oxford classification independently predicted long term ESRD.
.

Emergency Medical Services Utilization among Patients with ST-Segment Elevation Myocardial Infarction: Observations from the Singapore Myocardial Infarction Registry.

OBJECTIVE: Early activation of emergency medical services (EMS), rapid transport, and treatment of patients experiencing ST-segment elevation myocardial infarction (STEMI) can improve outcomes. The Singapore Myocardial Infarction Registry (SMIR) is a nation-wide registry that collects data on STEMI. We aimed to determine the prevalence, predictors, and outcomes of EMS utilization among STEMI patients presenting to Emergency Departments (ED) in Singapore. METHODS: We analyzed STEMI patients enrolled by SMIR from January 2010 to December 2012. We excluded patients who were transferred, developed STEMI in-hospital or suffered cardiac arrest out-of-hospital or in the ED. Primary outcome was process-of-care timings. Secondary outcomes included the occurrence of cardiac complications. Multivariate analysis was used to examine independent factors associated with EMS transport. RESULTS: 6412 patients were enrolled into the study; 4667 patients were eligible for analysis. 49.8% of patients utilized EMS transport. EMS transport was associated with higher rate of reperfusion therapy (74.3% vs. 65.1%, p < 0.01), shorter median symptom-to-door time (119 vs. 182 minutes, p < 0.01), door-to-balloon time (59 vs. 70 minutes, p < 0.01), and symptom-to-balloon time (185 vs. 233 minutes, p < 0.01). EMS transport had more patients with Killip Class 4 (7.5% vs 4.0%, p < 0.01) and was associated with greater presentation of heart failure, arrhythmias, and complete heart block. Independent predictors of EMS transport were age, syncope and Killip score; after-office-hour presentation was a negative predictor. CONCLUSION: Less than half of STEMI patients utilized EMS and EMS patients had faster receipt of initial reperfusion therapies. Targeted public education to reduce time to treatment may improve the care of STEMI patients.

Buckling up in Singapore: residency and other risk factors for seatbelt non-compliance - a cross-sectional study based on trauma registry data.

BACKGROUND: Seatbelt non-compliance is a problem in middle income countries, and little is known about seatbelt compliance in populations with a high proportion of non-residents. This study analyses the profile of seatbelt non-compliance in Singapore based on trauma registry data from five of the six public hospitals. METHODS: This is a cross-sectional study of seatbelt compliance of patients aged over 18 years, attending the emergency departments of five public hospitals in Singapore after road collisions from 2011-2014. Seatbelt data was obtained from paramedic and patient history. RESULTS: There were 4,576 patients studied. Most were Singapore citizens (83.4 %) or permanent residents (2.4 %), with the largest non-resident groups from Malaysia, India, and China. Overall seatbelt compliance was 82.1 %. On univariate analysis, seatbelt compliance was higher in older patients (OR 1.02, 95 % CI 1.001-1.021, p < 0.0001); drivers, followed by front passengers (OR 0.65, 95 % CI 0.51-0.83, p < 0.0001), were more compliant than rear passengers (OR 0.08, 0.06-0.09, p < 0.0001); occupants of larger vehicle types (buses, heavy transport vehicles, minibuses and vans) were more non-compliant compared to occupants of private cars and taxis. Morning peak travel (0700 h-0900 h) and being a non-resident were other risk factors for non-compliance. On multivariable analysis, older age (OR 1.01, 95 % CI 1.001-1.014, p = 0.03) was associated with compliance, while non-residents from China (OR 0.43, 95 % CI 0.18-0.99, p = 0.05), seat position (front passenger compared to driver, OR 0.64, 95 % CI 0.48-0.85, p = 0.002; rear passenger compared to driver, OR 0.067, 95 % CI 0.05-0.09, p < 0.0001), vehicle type (bus compared to car, OR 0.04, 95 % CI 0.017-0.11, p < 0.0001, van compared to car, OR 0.55, 95 % CI 0.36-0.83, p = 0.004), and travel at morning peak periods were independent predictors of seatbelt non-compliance. When the sub-group of drivers was analysed, only vehicle type was a significant predictor of seatbelt compliance, with bus drivers least likely to be compliant to seatbelts (multivariable analysis, OR 0.057 compared to cars, 95 % CI 0.019-0.18, p < 0.0001). CONCLUSIONS: While overall seatbelt compliance in our study is high, efforts can be made to increase compliance for morning rush hour passengers, rear seat passengers, and occupants of buses, heavy transport vehicles, and vans or pickups.

Trends in Stroke Incidence and 28-Day Case Fatality in a Nationwide Stroke Registry of a Multiethnic Asian Population.

BACKGROUND AND PURPOSE: This study investigated trends in stroke incidence and case fatality overall and according to sex, age, ethnicity, and stroke subtype in a multiethnic Asian population. METHODS: The Singapore Stroke Registry identifies all stroke cases in all public hospitals using medical claims, hospital discharge summaries, and death registry data. Age-standardized incidence rates and 28-day case-fatality rates were calculated for individuals aged ≥15 years between 2006 and 2012. To estimate the annual percentage change of the rates, a linear regression model was fitted to the log rates, and a Wald test was performed to test for trend. P values <0.05 were considered significant. RESULTS: A total of 40 623 cases were recorded. The total stroke incidence fell by ≈12.0%, and case fatality fell by 17.2% in the study. Declining trends in stroke incidence were stronger in women (female: -2.94; 95% confidence interval [CI], -3.43 to -2.44; male: -1.80; 95% CI, -2.58 to -1.02); in the older age groups (≥65 years: -3.62; 95% CI, -4.30 to -2.94; 50-64 years: -1.26; 95% CI, -1.97 to -0.55; <50 years: 3.33; 95% CI, 1.49 to 5.20), in Chinese (-2.64; 95% CI, -3.15 to -2.13), Indians (-3.78; 95% CI, -5.93 to -1.58), and others (-12.73; 95% CI, -18.93 to -6.06) compared with Malays (2.58; 95% CI, 1.17 to 4.02); and in ischemic stroke subtype (ischemic: -2.43; 95% CI, -3.13 to -1.73; hemorrhagic: -1.02; 95% CI, -2.04 to 0.01). Subgroup-specific findings for case fatality were similar. CONCLUSION: This is the first countrywide hospital-based registry study in a multiethnic Asian population, and it revealed marked overall reductions in stroke incidence and case fatality. However, it also identified important population groups with less favorable trends, especially younger adults and those of Malay ethnicity.

Gender and ethnic differences in incidence and survival of lymphoid neoplasm subtypes in an Asian population: Secular trends of a population-based cancer registry from 1998 to 2012.

Descriptive epidemiology on incidence and survival by lymphoid neoplasm (LN) subtypes using the 2008 World Health Organisation (WHO) classification remained limited in Asia. The aim of this study was to evaluate whether gender and ethnic differences in incidence and survival of LN subtypes existed using the Singapore Cancer Registry (SCR) from 1998 to 2012. We derived age standardised incidence rates (ASIRs) by the direct standardisation method and 5-year relative survival (RSR) by the Ederer II method and period approach. Five-year observed survival (OS) was obtained for each ethnicity. Malays had the highest ASIR of total LNs among the three ethnicities for each time period. The largest increase in 5-year RSR subtypes was follicular lymphoma from 43.8% in 1998-2002 to 82.3% in 2008-2012; followed by chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL) from 48.1% in 1998-2002 to 77.9% in 2008-2012. Although males had higher incidence than females in each time period, females had greater 5-year RSR for follicular lymphoma (89.8% in 2008-2012 for females vs. 76.6% in 2008-2012 for males) and CLL/SLL (78.7% in 2008-2012 for females vs. 76.7% in 2008-2012 for males). All three ethnicities experienced an overall increase in 5-year OS for mature B-cell lymphoma, with Indians experiencing the greatest increase (37.1% in 1998-2002 to 61.1% in 2008-2012), followed by Malays (30.8% in 1998-2002 to 48.7% in 2008-2012) and then Chinese (36.4% in 1998-2002 to 51.3% in 2008-2012). Our study demonstrated that improved mature B-cell lymphoma survival was not only observed in the West, but also in Singapore.

Reproductive factors, adiposity, breastfeeding and their associations with ovarian cancer in an Asian cohort.

PURPOSE: The aim of this study was to assess associations of breastfeeding, adiposity and reproductive risk factors with ovarian cancer risk in a Singaporean population. In addition to the main analysis, interaction effects of parity on other risk factors were examined. METHODS: A retrospective cohort consisting of 28,201 women with 107 incident ovarian cancers in up to 17 years of follow-up from the Singapore Breast Cancer Screening Project (1994-1997) was studied. Hazard ratios (HRs) for risk factors were estimated using Cox proportional hazards models. RESULTS: Body mass index and breastfeeding were found to have no statistical significant association with ovarian cancer risk. Gravidity was inversely associated with ovarian cancer risk [each pregnancy, adjusted HR 0.89, 95% confidence interval (CI) 0.81, 0.97], while results for parity were very similar (per delivery, HR 0.89, 95% CI 0.81, 0.98). Each additional year of ovulatory period was found to increase ovarian cancer risk by 2% (HR 1.02, 95% CI 1.00, 1.04). Each year increase in total duration of oral contraceptive use reduced ovarian cancer risk by 6% (HR 0.94, 95% CI 0.85, 1.02). CONCLUSIONS: Parity, gravidity and shorter ovulatory period were associated with lower ovarian cancer risk. Breastfeeding and body mass index were not associated with ovarian cancer risk, while increased duration of oral contraceptive use resulted in borderline risk reduction. No significant evidence was found to suggest that parity had an interaction effect on any risk factor.

Physical activity and risk of end-stage kidney disease in the Singapore Chinese Health Study.

AIM: To explore the relationship between physical activity and risk of end-stage kidney disease (ESKD). METHODS: We analysed data on a prospective cohort of 59,552 Chinese adults aged 45-74 years enrolled in the Singapore Chinese Health Study. Information on physical activity was collected with a structured questionnaire. Physically active individuals were defined as those who engaged in any moderate activities for 2 h or more per week and any strenuous activities 30 min or more per week. Incident ESKD was identified via record linkage with the Singapore Registry of Birth and Death and Singapore Renal Registry. Cox proportional hazards regression method was used for analysis for risk of incident ESKD alone or ESKD plus death associated with physical activity. RESULTS: During a median follow-up of 15.3 years, a total of 642 incident ESKD occurred, and 9808 study participants died. A 24% lower adjusted risk of ESKD (hazard ratio: 0.76; 95% confidence interval: 0.62-0.93) was associated with moderate or strenuous physical activities compared with no regular physical activity. This association appeared to be dose dependent with the lowest risk for subjects at highest intensity of physical activity (P trend <0.003). Similar results were observed for risk of ESKD plus death. CONCLUSION: Higher levels of physical activity are associated with lower risk of ESKD. Our findings highlight the role of physical activity for prevention of ESKD, which deserves further evaluation in intervention trials.

Mortality of older persons living alone: Singapore Longitudinal Ageing Studies.

BACKGROUND: We 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. METHOD: Using 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. RESULTS: At 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). CONCLUSION: Living 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.

Retinal microvascular changes and risk of stroke: the Singapore Malay Eye Study.

BACKGROUND AND PURPOSE: To examine the relationship between retinal microvascular measures and incident stroke in an Asian Malay population. METHODS: We conducted a prospective, population-based cohort study of Asian Malay persons 40 to 80 years at baseline. Retinal microvascular signs were assessed from baseline retinal photographs including quantitative retinal microvascular parameters (caliber, branching angle, tortuosity, and fractal dimension) and qualitative retinopathy signs. Incident stroke cases were identified during the follow-up period. Cox proportional-hazards regression and incremental usefulness analysis (calibration, discrimination, and reclassification) were performed. RESULTS: A total of 3189 participants were free of prevalent stroke at baseline. During the follow-up (median, 4.41 years), 51 (1.93%) participants had an incident stroke event. In Cox proportional-hazards models adjusting for established stroke predictors (age, sex, systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, smoking, glycosylated hemoglobin, and antihypertensive medication), retinopathy (hazard ratio, 1.94; 95% confidence interval, 1.01-3.72) and larger retinal venular caliber (hazard ratio, 3.28; 95% confidence interval, 1.30-8.26, comparing fourth versus first quartiles) were associated with risk of stroke. Compared with the model with only established risk factors, the addition of retinal measures improved the prediction of stroke (C-Statistic 0.826 versus 0.792; P=0.017) and correctly reclassified 5.9% of participants with incident stroke and 3.4% of participants with no incident stroke. CONCLUSIONS: Retinal microvascular changes are related to an increased risk of stroke in Asian Malay, consistent with data from white populations. Retinal imaging improves the discrimination and stratification of stroke risk beyond that of established risk factors by a significant but small margin.

Validation of the Gail model for predicting individual breast cancer risk in a prospective nationwide study of 28,104 Singapore women.

INTRODUCTION: The Gail model (GM) is a risk-assessment model used in individual estimation of the absolute risk of invasive breast cancer, and has been applied to both clinical counselling and breast cancer prevention studies. Although the GM has been validated in several Western studies, its applicability outside North America and Europe remains uncertain. The Singapore Breast Cancer Screening Project (SBCSP) is a nation-wide prospective trial of screening mammography conducted between Oct 1994 and Feb 1997, and is the only such trial conducted outside North America and Europe to date. With the long-term outcomes from this study, we sought to evaluate the performance of GM in prediction of individual breast cancer risk in a Asian developed country. METHODS: The study population consisted of 28,104 women aged 50 to 64 years who participated in the SBSCP and did not have breast cancer detected during screening. The national cancer registry was used to identify incident cases of breast cancer. To evaluate the performance of the GM, we compared the expected number of invasive breast cancer cases predicted by the model to the actual number of cases observed within 5-year and 10-year follow-up. Pearson's Chi-square test was used to test the goodness of fit between the expected and observed cases of invasive breast cancers. RESULTS: The ratio of expected to observed number of invasive breast cancer cases within 5 years from screening was 2.51 (95% confidence interval 2.14 - 2.96). The GM over-estimated breast cancer risk across all age groups, with the discrepancy being highest among older women aged 60 - 64 years (E/O = 3.53, 95% CI = 2.57-4.85). The model also over-estimated risk for the upper 80% of women with highest predicted risk. The overall E/O ratio for the 10-year predicted breast cancer risk was 1.85 (1.68-2.04). CONCLUSIONS: The GM over-predicts the risk of invasive breast cancer in the setting of a developed Asian country as demonstrated in a large prospective trial, with the largest difference seen in older women aged between 60 and 64 years old. The reason for the discrepancy is likely to be multifactorial, including a truly lower prevalence of breast cancer, as well as lower mammographic screening prevalence locally.

Assessing risk of breast cancer in an ethnically South-East Asia population (results of a multiple ethnic groups study).

BACKGROUND: Gail and others developed a model (GAIL) using age-at-menarche, age-at-birth of first live child, number of previous benign breast biopsy examinations, and number of first-degree-relatives with breast cancer as well as baseline age-specific breast cancer risks for predicting the 5-year risk of invasive breast cancer for Caucasian women. However, the validity of the model for projecting risk in South-East Asian women is uncertain. We evaluated GAIL and attempted to improve its performance for Singapore women of Chinese, Malay and Indian origins. METHODS: Data from the Singapore Breast Screening Programme (SBSP) are used. Motivated by lower breast cancer incidence in many Asian countries, we utilised race-specific invasive breast cancer and other cause mortality rates for Singapore women to produce GAIL-SBSP. By using risk factor information from a nested case-control study within SBSP, alternative models incorporating fewer then additional risk factors were determined. Their accuracy was assessed by comparing the expected cases (E) with the observed (O) by the ratio (E/O) and 95% confidence interval (CI) and the respective concordance statistics estimated. RESULTS: From 28,883 women, GAIL-SBSP predicted 241.83 cases during the 5-year follow-up while 241 were reported (E/O=1.00, CI=0.88 to 1.14). Except for women who had two or more first-degree-relatives with breast cancer, satisfactory prediction was present in almost all risk categories. This agreement was reflected in Chinese and Malay, but not in Indian women. We also found that a simplified model (S-GAIL-SBSP) including only age-at-menarche, age-at-birth of first live child and number of first-degree-relatives performed similarly with associated concordance statistics of 0.5997. Taking account of body mass index and parity did not improve the calibration of S-GAIL-SBSP. CONCLUSIONS: GAIL can be refined by using national race-specific invasive breast cancer rates and mortality rates for causes other than breast cancer. A revised model containing only three variables (S-GAIL-SBSP) provides a simpler approach for projecting absolute risk of invasive breast cancer in South-East Asia women. Nevertheless its role in counseling the individual women regarding their risk of breast cancer remains problematical and needs to be validated in independent data.

Multiparity and the risk of premenopausal breast cancer: different effects across ethnic groups in Singapore.

BACKGROUND: The relationship between multiparity and premenopausal breast cancer risk is different in Caucasian, African-American and Hispanic women. For Asian women, this relationship has never been well studied. METHODS: Within the Singapore Birth Registry, we selected all women who had a first child between 1986 and 2002 (169,936 Chinese, 40,521 Malay, 17,966 Indian). We linked them to the Singapore Cancer Registry data to identify those who developed breast cancer after childbirth (n = 527). We used multivariate Cox analysis to examine the relationship between parity, ethnicity and premenopausal breast cancer risk. RESULTS: Compared to Chinese, Malay women had increased and Indian women had decreased risks of premenopausal breast cancer (adjusted Hazard Ratios [HRadj] 1.25 [1.0-1.6] and 0.48 [0.3-0.8] respectively). Multiparity did not modify the risk of premenopausal breast cancer in Chinese and Indians. In Malays there was a significant risk reduction with increasing parity (P (trend )0.037). Malay women with one, two and >or=3 children had premenopausal breast cancer risks (HR(adj)) of 1.86 (1.2-3.0), 1.52 (1.1-2.2) and 0.87 (0.6-1.3) respectively compared to their Chinese counterparts. CONCLUSIONS: The impact of multiparity on premenopausal breast cancer risk differs across ethnic groups in Singapore. Increasing parity reduces the risk of premenopausal breast cancer in Malay, but not in Chinese and Indian women. Uniparous Malay women have twice the risk of premenopausal breast cancer compared to uniparous Chinese. This excess risk disappears after giving birth to >or=3 children. Indian women have lower premenopausal breast cancer risks than Chinese, regardless of their parity status.

Incidence, risk factors and outcomes of malignancies after kidney transplantation in Singapore: a 12-year experience.

INTRODUCTION: Data on malignancy after kidney transplantation (KTX) is limited in our region, leading to challenges in the care of renal allograft recipients. We aimed to examine the epidemiology, risk factors and outcomes of post-KTX patients. METHODS: A retrospective cohort study was conducted of 491 patients who underwent KTX from 1 January 2000 to 31 December 2011. Data linkage analysis was done between our centre and the National Registry of Diseases Office to determine the standardised incidence ratio (SIR), standardised mortality ratio (SMR) and risk factors for malignancy after KTX. RESULTS: 31 patients (61.3% male) developed malignancy during this period, and their median age at diagnosis was 50 (range 18-65) years. Median time to malignancy diagnosis was 2.6 (range 0.3-7.9) years, with cumulative incidence of 1%, 4% and 10% at one, five and ten years, respectively. The commonest malignancy type was lymphoma, followed by kidney cancer, colorectal cancer and malignancy of the male genital organs. Multivariate analysis identified cyclosporine use as an independent risk factor for malignancy. Compared to the general population, KTX recipients had higher malignancy and mortality rates after malignancy diagnosis (SIR 3.36; SMR 9.45). Survival rates for KTX recipients with malignancy versus those without malignancy were 100%, 93% and 64% versus 97%, 93% and 83% at one, five and ten years, respectively. CONCLUSION: KTX was associated with higher mortality and incidence of malignancy. Newer immunosuppressive agents and induction therapies were not found to be risk factors for malignancy, possibly due to our relatively small sample size.

Reproductive factors, obesity and risk of colorectal cancer in a cohort of Asian women.

BACKGROUND: This study evaluated reproductive factors and obesity in relation to colorectal cancer (CRC) in Asian women. METHODS: The study cohort comprised 28191 women who were recruited between 1994 and 1997. During 18 years of prospective follow-up, 404 and 212 women developed colon cancer (CC) and rectal cancer (RC) respectively. Cox proportional hazards regression was used. RESULTS: Menstrual factors were not related to the risk of CRC, CC and RC. Gravidity and parity were not associated with CRC or RC, but women who were ever pregnant had a HR of 1.87 (95%CI 1.12-3.14) compared to those never pregnant, and parous women had a HR of 1.79 (95% CI 1.10-2.92) compared to nulliparous women for CC. Use of oral contraceptives and hormone replacement therapy were not associated with CRC, CC or RC. Compared to women with normal BMI, women who were obese had HRs of 1.39 (95%CI 1.12-1.74) and 1.64 (95%CI 1.24-2.16) for CRC and CC respectively. No increased risk was seen for RC. Adjusted for BMI, for colonic cancer, women in the highest quartile for Waist Circumference had a HR of 2.14 (95%CI 1.42-3.25) compared to the lowest quartile, for Waist Hip Ratio, a HR of 1.74 (95%CI 1.30-2.34), and for Waist-Height ratio, a HR of 1.80 (1.26-2.57). None of these measures were significantly associated with RC. CONCLUSIONS: Obesity is positively associated with CC but not RC, and abdominal obesity exerts an independent effect. Reproductive factors had at best a weak effect on CC and RC.

Ovarian Cancer Incidence in the Multi-Ethnic Asian City-State of Singapore 1968-2012.

PURPOSE: We investigate ovarian cancer incidence between 1968 and 2012 in Singapore, a multiethnic Asian city state. METHODS: Aggregated data of ovarian epithelial cancer numbers and estimated person-years from 1968 to 2012 were obtained from Singapore Cancer Registry. Age-Period-Cohort modelling was performed. RESULTS: The age-standardised incidence rate of ovarian cancer increased from 5.8 to 12.5 per 100,000 per year between 1968 and 2012, while the age-standardised mortality rate has remained stable. This increase was higher among Malays (5.1 to 14.0 per 100,000 per year), compared to Chinese and Indians.  Serous carcinoma showed the greatest increase in incidence from 0.4 to 3.4 per 100,000 per year.  Period effects were seen in the ovarian cancer incidence trend in Chinese women, but not Malay and Indian women. Clear cell and mucinous carcinoma subtypes were more common in Chinese than in Malay and Indian women. Stage at diagnosis for the years 2003-2010 differed by subtype, and the majority of patients with serous carcinomas presented at a later stage compared to those with clear cell or mucinous carcinomas. CONCLUSION: Ovarian cancer incidence rates have doubled in 40 years in Singapore. There were ethnic differences in incidence rates and ovarian cancer subtypes.

Age-dependent relationships between body mass index and mortality: Singapore longitudinal ageing study.

OBJECTIVES: The 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. METHOD: Prospective 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. RESULTS: Overall, 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). CONCLUSION: BMI 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.