Characterisation of protein-truncating and missense variants in PALB2 in 15 768 women from Malaysia and Singapore.

BACKGROUND: Rare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2 in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population. METHODS: Mutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays. RESULTS: PTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks. CONCLUSION: Despite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.

Cohort profile: The Singapore Breast Cancer Cohort (SGBCC), a multi-center breast cancer cohort for evaluation of phenotypic risk factors and genetic markers.

This article aims to provide a detailed description of the Singapore Breast Cancer Cohort (SGBCC), an ongoing multi-ethnic cohort established with the overarching goal to identify genetic markers for breast cancer risk, prognosis and treatment response, as well as to understand the ethnic differences in disease risk and outcome in an Asian setting. The cohort comprises of breast cancer patients aged 21 years and above from six public hospitals which diagnose and treat nearly 76% breast cancer cases in Singapore. Self-reported data on sociodemographic and lifestyle, reproductive risk factors, medical history and family history of breast or ovarian cancer is collected using a structured questionnaire. Clinical data on tumour characteristics, and treatment modalities are obtained through medical record. Bio-specimens (blood or saliva) is collected at recruitment. Follow-up on survival information is done through routine linkage with the Registry of Births and Deaths. As of 31 December 2016, 7,768 subjects have been recruited to the study with 76% subjects contributed bio-specimens. The SGBCC provides a valuable platform which offers a unique, large and rich resource for new research ideas on breast cancer related phenotypic risk factors and genetic markers.

Increased oral processing and a slower eating rate increase glycaemic, insulin and satiety responses to a mixed meal tolerance test.

PURPOSE: Variations in specific oral processing behaviours may contribute to differences in glucose, insulin and satiety responses to a standardised test meal. This study tested how natural variations in oral processing between slower and faster eaters contribute to differences in post-prandial glucose (PP glucose), insulin response (PP insulin) and post-meal satiety for a standardised test meal. METHODS: Thirty-three participants with higher risk for type 2 diabetes consumed a standardised test-meal while being video recorded to derive specific oral processing behaviours. Plasma glucose, insulin and satiety measures were collected at baseline, during and post meal. Participants were split into slower and faster eaters using median split based on their eating rates and individual bolus properties were analysed at the point of swallow. RESULTS: There were large variations in eating rate (p < 0.001). While there was no significant difference in PP glucose response (p > 0.05), slower eaters showed significantly higher PP insulin between 45 and 60 min (p < 0.001). Slower eaters had longer oro-sensory exposure and increased bolus saliva uptake which was associated with higher PP glucose iAUC. Faster eating rate and larger bolus particle size at swallow correlated with lower PP glucose iAUC. A slower eating rate with greater chews per bite significantly increased insulin iAUC. Faster eaters also consistently rated their hunger and desire to eat higher than slower eaters (p < 0.05). CONCLUSIONS: Natural variations in eating rate and the associated oral processing contributed to differences in PP glucose, PP insulin and satiety responses. Encouraging increased chewing and longer oral-exposure time during consumption, may promote early glucose absorption and greater insulin and satiety responses, and help support euglycaemia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04522063.

Development of a serum miRNA panel for detection of early stage non-small cell lung cancer.

Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects. Using RT-qPCR and a tightly controlled workflow, we quantified the absolute expression of 520 circulating microRNAs (miRNAs) in a Chinese cohort of 180 early stage NSCLC cases and 216 healthy controls (male smokers). Candidate biomarkers were verified in two case-control cohorts of 432 Chinese and 218 Caucasians, respectively (including females and nonsmokers). A multimiR panel for NSCLC detection was developed using a twofold cross-validation and validated in three additional Asian cohorts comprising 642 subjects. We discovered 35 candidate miRNA biomarkers, verified 22 of them, and developed a five-miR panel that detected NSCLC with area under curve (AUC) of 0.936-0.984 in the discovery and verification cohorts. The panel was validated in three independent cohorts with AUCs of 0.973, 0.916, and 0.917. The sensitivity of five-miR test was 81.3% for all stages, 82.9% for stages I and II, and 83.0% for stage I NSCLC, when the specificity is at 90.7%. We developed a minimally invasive five-miR serum test for detecting early stage NSCLC and validated its performance in multiple patient cohorts independent of smoking status, gender, and ethnicity.

Maternal Dietary Patterns and Birth Outcomes: A Systematic Review and Meta-Analysis.

Findings on the relations of maternal dietary patterns during pregnancy and risk of preterm birth and offspring birth size remain inconclusive. We aimed to systematically review and quantify these associations. We searched MEDLINE, Embase, CENTRAL, and CINAHL up to December 2017. Three authors independently conducted a literature search, study selection, data extraction, and quality assessment. Summary effect sizes were calculated with random effects models and studies were summarized narratively if results could not be pooled. We included 36 studies and pooled results from 25 observational studies (167,507 participants). Two common dietary patterns-"healthy" and "unhealthy"-were identified. Healthy dietary patterns-characterized by high intakes of vegetables, fruits, wholegrains, low-fat dairy, and lean protein foods-were associated with lower risk of preterm birth (OR for top compared with bottom tertile: 0.79; 95% CI: 0.68, 0.91; I2 = 32%) and a weak trend towards a lower risk of small-for-gestational-age (OR: 0.86; 95% CI: 0.73, 1.01; I2 = 34%). Only statistically data-driven healthy dietary patterns, and not dietary index-based patterns, were associated with higher birth weight (mean difference: 67 g; 95% CI: 37, 96 g; I2 = 75%). Unhealthy dietary patterns-characterized by high intakes of refined grains, processed meat, and foods high in saturated fat or sugar-were associated with lower birth weight (mean difference: -40 g; 95% CI: -61, -20 g; I2 = 0%) and a trend towards a higher risk of preterm birth (OR: 1.17; 95% CI: 0.99, 1.39; I2 = 76%). Data from observational studies indicate that greater adherence to healthy dietary patterns during pregnancy is significantly related to lower risk of preterm birth. No consistent associations with birth weight and small- or large-for-gestational-age were observed.

Associations between psychological factors and accelerometer-measured physical activity in urban Asian adults.

OBJECTIVES: Examine the association between psychological variables and accelerometer-measured moderate-to-vigorous physical activity (MVPA) in urban Asians. METHODS: A population-based cross-sectional study was conducted in Singapore. Participants wore an accelerometer for 7 days to measure physical activity (PA). Demographic, anthropometric and psychological data were also collected. Psychological variables included PA guideline knowledge, motivational profile for PA self-regulation (5 subscales), perceived barriers to PA (4 subscales) and perceived social support for PA. Regression models with adjustment for socio-demographic variables were fitted. RESULTS: External regulation (b = - 13.03, 95% CI - 34.55; - 1.50) and perceived daily life barriers (b = - 12.63, 95% CI - 24.95; - 0.32) were significantly associated with fewer weekly MVPA minutes. A significant interaction between perceived social support and age (p = 0.046) was found. Social support was significantly negative associated with MVPA minutes in younger (< 28 years), but not in older participants. CONCLUSIONS: Considering levels of self-determination to engage in PA and perceived daily life barriers may be important for planning PA interventions in urban Asian populations. Caution is required when promoting social support for PA as it was associated with lower MVPA in younger people.

Chronotype: Implications for Epidemiologic Studies on Chrono-Nutrition and Cardiometabolic Health.

Chrono-nutrition is an emerging research field in nutritional epidemiology that encompasses 3 dimensions of eating behavior: timing, frequency, and regularity. To date, few studies have investigated how an individual's circadian typology, i.e., one's chronotype, affects the association between chrono-nutrition and cardiometabolic health. This review sets the directions for future research by providing a narrative overview of recent epidemiologic research on chronotype, its determinants, and its association with dietary intake and cardiometabolic health. Limited research was found on the association between chronotype and dietary intake in infants, children, and older adults. Moreover, most of the evidence in adolescents and adults was restricted to cross-sectional surveys with few longitudinal cohorts simultaneously collecting data on chronotype and dietary intake. There was a gap in the research concerning the association between chronotype and the 3 dimensions of chrono-nutrition. Whether chronotype modifies the association between diet and cardiometabolic health outcomes remains to be elucidated. In conclusion, further research is required to understand the interplay between chronotype, chrono-nutrition, and cardiometabolic health outcomes.

Psychometric properties and population norms of the positive mental health instrument in a representative multi-ethnic Asian population.

BACKGROUND: Measures of mental well-being and positive mental health (PMH) have been largely developed and used in Western populations, however, data on representative Asian communities are lacking. Using data from a population sample, this study sought to establish psychometric properties and norms of the PMH Instrument (PMH-I), a measure of positive mental health developed in Singapore. METHODS: We conducted a nationally representative survey among 1925 adults aged 18-79 years of Chinese, Malay, Indian or other ethnicity. Participants reported socio-demographic characteristics and completed the PMH-I along with measures of health-related quality of life (HRQoL) and psychological distress. Construct validity of the PMH-I was assessed using confirmatory factor analysis and concurrent validity was tested through correlation with other psychological measures. Normative PMH values and differences in population subgroups were estimated. RESULTS: The six-factor-higher-order structure of the PMH-I comprising six subscales of general coping, emotional support, spirituality, interpersonal skills, personal growth and autonomy and global affect was confirmed. Concurrent validity was shown through significant positive correlation of the total PMH score and its subscales with HRQoL and an inverse correlation with psychological distress. Weighted age, gender and ethnicity-specific norms were derived for the Singapore population. Total PMH was significantly higher in participants aged over 40 years as compared with 18-29 year olds and in non-Chinese ethnic groups as compared with Chinese. These differences were observed for all PMH-I subscales, with the exception of emotional support and interpersonal skills score differences by age. In contrast, gender, marital status, and education level were significantly associated with some of the subscales, but not with total PMH. CONCLUSIONS: These results support the psychometric properties of the PMH-I in a multi-ethnic Asian population sample. The generalizable population-based norms support the application of the PMH-I for measuring mental health and assessing its determinants within the Singapore general population.

"Sometimes they'll tell me what they want": family and inter-generational food preferences in the food decisions of Singaporean women.

This study examines responses to questions regarding food choices and decisions from 18 focus groups of women (n=130) age 30-55 years living in Singapore. Focusing on the responses to the questions in the interview protocol closely associated with decision making identified several themes. Food choices and eating decisions are composite phenomenon. These composite food decisions reflect flexible, open systems we refer to here as idiosyncratic regimes in which environmental, social, and intra-personal streams of influence are prioritized as individuals generate possible food decisions. Food decisions represent the imagined and actual presence of the "family" and differing inter-generational food preferences. As women attempt to create harmony from the diversity of food preferences they generate idiosyncratic regimes of food and eating reflecting "triadic streams of influence" manifest in the context of everyday contingencies of family and individual life. Recent concern in Singapore on the part of the Health Promotion Board and the Saw Swee Hock School of Public Health at the National University of Singapore regarding the increasing prevalence of diet-related diseases and obesity among Singaporeans provided the impetus for conducting this qualitative study of food and eating among Singaporean women.