Reproductive factors and risk of epithelial ovarian cancer: results from the Asia Cohort Consortium.

Background: There are scarce data on risk factors for epithelial ovarian cancer (EOC) in Asian populations. Our goal was to advance knowledge on reproductive -related risk factors for EOC in a large population of Asian women.

Methods: This study used pooled individual data from baseline questionnaires in 11 prospective cohorts (baseline years, 1958-2015) in the Asia Cohort Consortium.

The Epstein-Barr Virus Nuclear Antigen 1 Variant Associated with Nasopharyngeal Carcinoma Defines the Sequence Criteria for Serologic Risk Prediction.

Purpose: Antibodies to select Epstein-Barr virus proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against Epstein-Barr virus nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years before diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay.

Consumption of different types of meat and the risk of chronic limb-threatening ischemia: the Singapore Chinese Health Study.

Background: Although red meat consumption has been associated with risk of atherosclerotic coronary artery disease and stroke, no prospective study has examined this with the risk of chronic limb-threatening ischemia (CLTI).

Methods: In a prospective study of 63,257 Chinese in Singapore, who were aged 45-74 years old at recruitment, diet was assessed via a validated semi-quantitative food frequency questionnaire. Incident CLTI cases were ascertained via linkage with nationwide hospital records for lower extremity amputation or angioplasty for peripheral arterial disease.

Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes.

While rapid demographic changes in Asia are driving the incidence of chronic aging-related diseases, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun-metagenomic sequencing for high-resolution taxonomic and functional characterization of their gut microbiomes (n = 234). Joint species-level analysis with other Asian cohorts identified distinct age-associated shifts characterized by reduction in microbial richness, and specific Alistipes and Bacteroides species enrichment (e.

Comparison of race- and ethnicity-specific BMI cutoffs for categorizing obesity severity: a multicountry prospective cohort study.

Objective: The objective of this study was to compare race- and ethnicity-specific BMI cutoffs for the three classes of obesity based on equivalent risk of type 2 diabetes (T2D).

Methods: Participants without T2D were included from the UK Biobank, the China Health and Nutrition Survey, and the Singapore Chinese Health Study. Poisson regressions with restricted cubic splines were applied to determine BMI cutoffs for each non-White race and ethnicity for equivalent incidence rates of T2D at BMI values of 30.

The Causal Effect of Adult Height on Late-Life Handgrip Strength: The Singapore Chinese Health Study.

Background: Adult height has been associated with handgrip strength, which is a surrogate marker of physical frailty. However, it is uncertain if this association is causative or due to confounding bias.

Methods: We evaluated pairwise associations among handgrip strength, adult height, and genetically determined height (using a polygenic score [PGS] for height in a mediation framework and a 2-sample Mendelian randomization approach) by means of a multivariable regression model using a prospective cohort of Chinese living in Singapore.

Healthcare burden of cognitive impairment: Evidence from a Singapore Chinese health study.

Background: Cognitive impairment (CI) raises risks for unplanned healthcare utilisation and expenditures and for premature mortality. It may also reduce risks for planned expenditures. Therefore, the net cost implications for those with CI remain unknown.

Characterizing the Relationship between Expression Quantitative Trait Loci (eQTLs), DNA Methylation Quantitative Trait Loci (mQTLs), and Breast Cancer Risk Variants.

Purpose: To assess the association of a polygenic risk score (PRS) for functional genetic variants with the risk of developing breast cancer.

Methods: Summary data-based Mendelian randomization (SMR) and heterogeneity in dependent instruments (HEIDI) were used to identify breast cancer risk variants associated with gene expression and DNA methylation levels. A new SMR-based PRS was computed from the identified variants (functional PRS) and compared to an established 313-variant breast cancer PRS (GWAS PRS).

Diet quality from mid to late life and its association with physical frailty in late life in a cohort of Chinese adults.

Background: It is unclear if improving diet quality after midlife could reduce the risk of physical frailty at late life. We aimed to associate changes in diet quality after midlife with physical frailty at late life.

Methods: Diet quality in 12,580 participants from the Singapore Chinese Health Study was assessed with the Dietary Approaches to Stop Hypertension (DASH) scores at baseline (1993-1998; mean age 53 years) and follow-up 3 (2014-2016; mean age 73 years).

Association between Dietary Antioxidant Capacity in Midlife and Depressive Symptoms in Late Life: The Singapore Chinese Health Study.

Preclinical and limited epidemiological studies suggest that oxidative stress may be implicated in geriatric depression. Our study investigated the association between midlife dietary total antioxidant capacity (TAC) and depressive symptoms in late life among 13,712 participants in a population-based cohort of Chinese in Singapore. At baseline (1993-1998), intake of antioxidants from diet and supplements at a mean age of 52.

Reproductive factors and risk of physical frailty among Chinese women living in Singapore.

Setting: Although age at menopause has been linked to higher risk of physical frailty in later life, little is known about other reproductive factors.

Objectives: Our study aimed to investigate the associations between 1) age at menarche, 2) age at natural menopause, 3) duration of reproductive period, 4) number of children, 5) use of oral contraceptives (OCP), and 6) use of hormone replacement therapy (HRT) with the risk of physical frailty in late life.

Design: We used data from 5934 women of the Singapore Chinese Health Study who experienced natural menopause, and participated in the third follow-up interviews when physical frailty was assessed.

Low-Carbohydrate Diet Score and Risk of Hepatocellular Carcinoma: Findings from a Prospective Cohort Study.

Unlabelled: Limited data are reported on the association between low-carbohydrate diet (LCD) score, a comprehensive measure of dietary pattern according to sources of carbohydrate, fat, and protein, and risk of hepatocellular carcinoma (HCC). We evaluated this score with HCC risk in the Singapore Chinese Health Study, a prospective cohort of 63,275 middle-aged and elderly Chinese living in Singapore and recruited during 1993-1998 period. LCD scores were derived from the semi-quantitative food frequency questionnaire at baseline.

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium.

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium.

A Pre-Leukemic DNA Methylation Signature in Healthy Individuals at Higher Risk for Developing Myeloid Malignancy.

Purpose: DNA methylation alterations are widespread in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), some of which appear to have evolved independently of somatic mutations in epigenetic regulators. Although the presence of somatic mutations in peripheral blood can predict the risk of development of AML and MDS, its accuracy remains unsatisfactory.

Experimental Design: We performed global DNA methylation profiling in a case control study nested within the Singapore Chinese Health Study to evaluate whether DNA methylation alterations were associated with AML/MDS development.

Higher handgrip strength is linked to higher salience ventral attention functional network segregation in older adults.

Converging evidence suggests that handgrip strength is linked to cognition in older adults, and this may be subserved by shared age-related changes in brain function and structure. However, the interplay among handgrip strength, brain functional connectivity, and cognitive function remains poorly elucidated. Hence, our study sought to examine these relationships in 148 community-dwelling older adults.

BMI and breast cancer risk around age at menopause.

Background: A high body mass index (BMI, kg/m) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology.