Chuen Seng Tan

Profound changes in breast cancer incidence may reflect changes into a Westernized lifestyle: a comparative population-based study in Singapore and Sweden.

Breast cancer incidence in Sweden has always been approximately twice as high as in Singapore. In recent years, this difference is limited to postmenopausal women. The aim of this study was to explore the reasons behind these differences through the use of age‐period‐cohort modeling. This population‐based study included all breast cancer cases reported to the Swedish and the Singapore cancer registries from 1968 to 1997, with a total of 135,581 Swedish and 10,716 Singaporean women. Poisson regression using age‐period and age‐cohort models was used to determine the effects of age at diagnosis, calendar period and birth cohort. Incidence rate ratios were used to summarize these effects. An age‐cohort model provided the best fit to the data in both countries, indicating that changes over lifetime, rather than recent differences in medical surveillance, might account for the observed differences in these 2 populations. The changes over birth cohort were much greater among Singaporean women. The relative effect of age was very similar in the 2 countries. Analyses show that age and cohort effects may explain the differences in trends of female breast cancer incidence between Sweden and Singapore. The larger cohort effect seen in Singaporean women may be attributed to more rapid changes in reproduction and lifestyle patterns than that of Swedish women during the period studied. The incidence of breast cancer in postmenopausal women in Singapore will probably continue to rise in the coming decades to match the current Swedish rates.

APOE polymorphism and lipid profile in three ethnic groups in the Singapore population

BACKGROUND Serum lipid concentrations are modulated by environmental factors such as exercise, alcohol intake, smoking, obesity and dietary intake and genetic factors. Polymorphisms at the Apolipoprotein E (APOE) locus have consistently shown a significant association with total and LDL-cholesterol (LDL-C). However, their impact on HDL-cholesterol (HDL-C) may be population dependent. Having three major ethnic groups within a similar social environment allows us to study the role of genetics and their interactions with lifestyle factors on the serum lipid profile and coronary risk in Asians. METHODS This study included 1740 males (1146 Chinese, 327 Malays and 267 Asian Indians) and 1950 females (1329 Chinese, 360 Malays and 261 Asian Indians) with complete data on anthropometric indices, fasting lipids, smoking status, alcohol consumption, exercise frequency and genotype at the APOE locus. RESULTS Malays and Asian Indians were more obese compared with the Chinese. Smoking was uncommon in all females but Malay males had significantly higher prevalence of smokers. Malays had the highest LDL-C whilst Indians had the lowest HDL-C, The epsilon 3 allele was the most frequent allele in all three ethnic groups. Malays had the highest frequency of epsilon 4 (0.180 and 0.152) compared with Chinese (0.085 and 0.087) and Indians (0.108 and 0.075) in males and females, respectively. The epsilon 2 allele was the least common in Asian Indians. Total cholesterol (TC) and LDL-C was highest in epsilon 4 carriers and lowest in epsilon 2 carriers. The reverse was seen in HDL-C with the highest levels seen in epsilon 2 subjects. The association between ethnic group and HDL-C differed according to APOE genotype and gender. Asian Indians had the lowest HDL-C for each APOE genotype except in Asian Indian males with epsilon 2, where HDL-C concentrations were intermediate between Chinese and Malays. CONCLUSION Ethnic differences in lipid profile could be explained in part by the higher prevalence of epsilon 4 in the Malays. Ethnicity may influence the association between APOE genotypes and HDL-C. APOE genotype showed no correlation with HDL-C in Malay males whereas the association in Asian Indians was particularly marked. Further studies of interactions between genes and environmental factors will contribute to the understanding of differences of coronary risk amongst ethnic groups.

Secular trends of nasopharyngeal carcinoma incidence in Singapore, Hong Kong and Los Angeles Chinese populations, 1973-1997

Nasopharyngeal carcinoma (NPC) is a rare cancer in most parts of world, but rather common in Southern China and Southeast Asia. This study used IARC published datasets to explore the secular trends of incidence rates of NPC among different Chinese populations in Singapore, Hong Kong and Los Angeles, over the time period 1973–1997. We observed great disparity in the risks and time trends of NPC in those selected Chinese populations. The highest risk was in Hong Kong where the incidence rates have declined rapidly throughout the whole study period in both males and females. For Singapore Chinese, the incidence rates also dropped recently in both genders, but the low incidence rates in Los Angeles Chinese have remained essentially unchanged over time. We further assessed the contribution of period and cohort effects to the observed trends in Hong Kong and Singapore populations through age-period-cohort modeling and found that an age-cohort model provided the best fit to the data in both populations, although for Singapore females a simple age-drift model fit the data well. There was a statistically significant decrease in the drop in incidence of NPC for cohorts born around 1940 in Hong Kong and 1958 in Singapore. This indicates that environmental and lifestyle changes play an important role in the declining incidence of NPC over time.

Ethnic differences in the time trend of female breast cancer incidence: Singapore, 1968 – 2002

BackgroundFrom 1968 to 2002, Singapore experienced an almost three-fold increase in breast cancer incidence. This increase appeared to be different across the three main ethnic groups: Chinese, Malays and Indians. This paper used age-period-cohort (APC) modelling, to determine the effects of age at diagnosis, calendar period, and birth cohort on breast cancer incidence for each ethnic group.MethodsThis study included all breast cancer cases (n = 15,269) in the three ethnic groups, reported to the Singapore Cancer Registry from 1968 to 2002 between the ages 25 to 79. Age-specific fertility rates from the Department of Statistics were used to explore the role of fertility.ResultsIn the 1970s, Indian women had the highest age-standardized breast cancer but by the mid-1980s the highest rates were seen among the Chinese. Remarkable differences were seen in the age-specific incidence rates by ethnic groups. After age 49, the incidence rates for the Chinese and Malays leveled off whereas it continued to rise in the Indians. While our analyses provided some evidence that an age-drift model described the trend seen in the Indians, age-period-cohort model and age-cohort model had the best fit for the Chinese and Malays aged 25 to 79 respectively. Overall, Chinese and Malay women born in later cohorts were at increased risk of developing breast cancer relative to their counterparts in the earlier cohorts. The three ethnic groups experienced similar changes in their fertility in the 1970s, which likely explained much of the increase in their breast cancer incidence but not the ethnic differences. There was a stronger inverse association between total fertility rate and pre-menopausal breast cancer incidence in the Chinese and Malays than the Indians.ConclusionThe observed dissimilarity among ethnic groups suggests ethnic differences in exposure or response to certain risk factors. It is likely that longer and subtler differences in childbearing trends and other risk factors may further explain these ethnic differences.

Identification of Specific Cell-Surface Markers of Adipose-Derived Stem Cells from Subcutaneous and Visceral Fat Depots

Summary Adipose-derived stem/stromal cells (ASCs) from the anatomically distinct subcutaneous and visceral depots of white adipose tissue (WAT) differ in their inherent properties. However, little is known about the molecular identity and definitive markers of ASCs from these depots. In this study, ASCs from subcutaneous fat (SC-ASCs) and visceral fat (VS-ASCs) of omental region were isolated and studied. High-content image screening of over 240 cell-surface markers identified several potential depot-specific markers of ASCs. Subsequent studies revealed consistent predominant expression of CD10 in SC-ASCs and CD200 in VS-ASCs across 12 human subjects and in mice. CD10-high-expressing cells sorted from SC-ASCs differentiated better than their CD10-low-expressing counterparts, whereas CD200-low VS-ASCs differentiated better than CD200-high VS-ASCs. The expression of CD10 and CD200 is thus depot-dependent and associates with adipogenic capacities. These markers will offer a valuable tool for tracking and screening of depot-specific stem cell populations.

A systematic review and meta-analysis of workplace intervention strategies to reduce sedentary time in white-collar workers.

Prolonged sedentary behaviour has been associated with various detrimental health risks. Workplace sitting is particularly important, providing it occupies majority of total daily sedentary behaviour among desk‐based employees. The aim of this systematic review and meta‐analysis was to examine the effectiveness of workplace interventions overall, and according to different intervention strategies (educational/behavioural, environmental and multi‐component interventions) for reducing sitting among white‐collar working adults. Articles published through December 2015 were identified in five online databases and manual searches. Twenty‐six controlled intervention studies published between 2003 and 2015 of 4568 working adults were included. All 26 studies were presented qualitatively, and 21 studies with a control group without any intervention were included in the meta‐analysis. The pooled intervention effect showed a significant workplace sitting reduction of −39.6 min/8‐h workday (95% confidence interval [CI]: −51.7, −27.5), favouring the intervention group. Multi‐component interventions reported the greatest workplace sitting reduction (−88.8 min/8‐h workday; 95% CI: −132.7, −44.9), followed by environmental (−72.8 min/8‐h workday; 95% CI: −104.9, −40.6) and educational/behavioural strategies −15.5 min/8‐h workday (95% CI:−22.9,−8.2). Our study found consistent evidence for intervention effectiveness in reducing workplace sitting, particularly for multi‐component and environmental strategies. Methodologically rigorous studies using standardized and objectively determined outcomes are warranted.

The lipoprotein lipase S447X polymorphism and plasma lipids interactions with APOE polymorphisms, smoking, and alcohol consumption

We studied 4,058 subjects from a representative sample of the Singapore population 1) to determine the association between the S447X polymorphism at the LPL locus and serum lipid concentration in Chinese, Malays, and Asian Indians living in Singapore and 2) to explore any interactions with apolipoprotein E (APOE) genotype, exercise, obesity, cigarette smoking, and alcohol intake. Information on obesity, lifestyle factors (including smoking, alcohol consumption, and exercise frequency), glucose tolerance, and fasting lipids was obtained. Male and female carriers of the X447 allele had lower serum triglyceride concentrations and higher HDL cholesterol (HDL-C) concentrations. The association between the X447 allele and serum HDL-C concentration was modulated by APOE genotype in males and cigarette smoking and alcohol intake in females. The effect of the X447 allele was greatest in men who carried the E4 allele and women who smoked or consumed alcohol. The X447 allele at the LPL locus is common and associated with a less atherogenic lipid profile in Asian populations. Interactions with APOE genotype, cigarette smoking, and alcohol intake reinforce the importance of examining genetic associations, such as this one, in the context of the population of interest.

Prevalence of cognitive impairment in Chinese: Epidemiology of Dementia in Singapore study

Objective To study the prevalence of and associated factors for cognitive impairment and dementia in community dwelling Chinese from Singapore. Methods This study includes Chinese subjects from the Epidemiology of Dementia in Singapore (EDIS) study, aged ≥60 years, who underwent comprehensive examinations, including cognitive screening with the locally validated Abbreviated Mental Test and Progressive Forgetfulness Questionnaire. Screen positive participants subsequently underwent extensive neuropsychological testing and cerebral MRI. Cognitive impairment no dementia (CIND) and dementia were diagnosed according to internationally accepted criteria. The prevalence of cognitive impairment and dementia were computed per 5 year age categories and gender. To examine the relationship between baseline associated factors and cognitive impairment, we used logistic regression models to compute odd ratios with 95% CI. Results 1538 Chinese subjects, aged ≥60 years, underwent cognitive screening: 171 (15.2%) were diagnosed with any cognitive impairment, of whom 84 were CIND mild, 80 CIND moderate and seven had dementia. The overall age adjusted prevalence of CIND mild was 7.2%; CIND moderate/dementia was 7.9%. The prevalence increased with age, from 5.9% in those aged 60–64 years to 31.3% in those aged 75–79 years and 44.1% in those aged ≥80 years. Multivariate analysis revealed age, diabetes and hyperlipidaemia to be independently associated with cognitive impairment. Conclusions In present study, the overall prevalence of cognitive impairment and dementia in Chinese was 15.2%, which is in the same range as the prevalence reported in Caucasian and other Asian populations.

Dissecting inflammatory complications in critically injured patients by within-patient gene expression changes: a longitudinal clinical genomics study.

By studying gene expression changes over time in a cohort of trauma patients, Keyur Desai and colleagues identify genes and pathways strongly associated with longer-term complications, which could lead to improved outcome prediction in the first 80 hours after injury.

Cerebral microbleeds and cognition: The epidemiology of dementia in singapore study

Cerebral microbleeds (CMBs) are considered to be a novel marker of cerebral small vessel disease. However, the link with cognitive impairment remains unclear. We investigated whether CMBs—independent of other traditional markers of cerebral small vessel disease—are related to cognition. Chinese subjects from the population-based Singapore Chinese Eye Study, who failed an initial cognitive screening and were recruited into the ongoing Epidemiology of Dementia in Singapore Study, underwent neuropsychological testing and 3 T brain magnetic resonance imaging. The presence and number of CMBs were graded using Brain Observer Microbleed Scale on susceptibility-weighted images. Other magnetic resonance imaging lesions that were graded included presence of lacunes, white matter lesion, and total brain volumes. A comprehensive neuropsychological battery was administered and cognitive function was summarized as composite and domain-specific Z-scores. Among 282 subjects, 91 had any CMBs (32.3%), of whom 36 (12.8%) had multiple CMBs. CMBs were—independent of cardiovascular risk factors and other markers of cerebral small vessel disease—significantly associated with poorer cognitive function as reflected by composite Z-score (mean difference per CMB increase: −0.06; 95% confidence interval: −0.11, −0.01] and with domain-specific Z-scores including executive function, attention, and visuoconstruction. Among Chinese subjects CMBs were, independent of other concomitant markers of cerebral small vessel disease, associated with poorer cognitive function.