Reproductive Factors and Endometrial Cancer Risk Among Women.

Importance: Despite evidence of an association between reproductive factors and endometrial cancer risk, prospective studies have been conducted mainly in non-Asian countries. Objective: To assess the association between reproductive factors, such as number of deliveries, age at menarche, or menopause, and endometrial cancer risk. Design, Setting, and Participants: This cohort study used pooled individual data from 13 prospective cohort studies conducted between 1963 and 2014 in the Asia Cohort Consortium. Participants were Asian women. Data analysis was conducted from September 2019 to April 2023. Exposures: Reproductive factors were assessed using a questionnaire in each cohort. Main Outcomes and Measures: The main outcome was time to incidence of endometrial cancer. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% CIs. Results: A total of 1005 endometrial cancer cases were detected among 332 625 women (mean [SD] age, 54.3 [10.4] years) during a mean (SD) of 16.5 (6.4) years of follow-up. Increasing number of deliveries was associated with a decreased endometrial cancer risk in a dose-response manner (≥5 deliveries vs nulliparous [reference]: HR, 0.37; 95% CI, 0.26-0.53; P for trend < .001). Compared with menarche at younger than 13 years, menarche at 17 years or older had an HR of 0.64 (95% CI, 0.48-0.86; P for trend < .001). Late menopause (age ≥55 years) showed an HR of 2.84 (95% CI, 1.78-4.55; P for trend < .001) compared with the youngest age category for menopause (<45 years). Age at first delivery, hormone therapy, and breastfeeding were not associated with endometrial cancer risk. Conclusions and Relevance: This large pooled study of individual participant data found that late menarche, early menopause, and a higher number of deliveries were significantly associated with a lower risk of endometrial cancer. These convincing results from Asian prospective studies add to the growing body of evidence for the association between reproductive factors and endometrial cancer.

Nutrition and Healthy Ageing in Asia: A Systematic Review.

BACKGROUND: Nutrition plays a key role in modulating the likelihood of healthy ageing. In the present study, we aimed to conduct a systematic review to assess the impact of nutrition on healthy ageing in Asia. METHODS: The systematic review was registered in the International Prospective Register of Systematic Reviews database (CRD42023408936) and conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Web of Science, and Embase databases were searched up to February 2023 without language restrictions. We included prospective cohort studies that evaluated the associations of intake of a single food or consumption of a single nutrient at midlife; adherence to various dietary patterns at midlife; and improved adherence to dietary patterns from mid- to late life with the likelihood of healthy ageing and its components. RESULTS: Out of 16,373 records, we included 71 papers comprising 24 cohorts from Singapore, China, Japan, and Thailand. The healthy ageing components included cognitive function, physical function, and depression. The majority of studies supported the observation that the likelihood of healthy ageing and its components in late life was positively increased by a higher consumption of healthy foods, such as vegetables, fruits, fish, nuts, legumes, tea, milk, and dairy, at midlife, and also by greater adherence to dietary patterns with high diversity scores or high total antioxidant capacities. Furthermore, improved adherence to healthy dietary patterns from mid- to late life also increased the likelihood of healthy ageing in late life. CONCLUSION: Consuming healthy foods and adhering to healthy dietary patterns at midlife can promote the likelihood of healthy ageing. Moreover, improving diet quality from mid- to late life can still be beneficial.

The Association Between Serum Riboflavin and Flavin Mononucleotide With Pancreatic Cancer: Findings From a Prospective Cohort Study.

OBJECTIVES: Vitamin B2 (riboflavin) has a prime role in metabolic reactions imperative to cell cycle and proliferation. We investigated the associations between serum concentrations of riboflavin flavin mononucleotide with the risk of pancreatic cancer in a nested case-control study involving 58 cases and 104 matched controls. METHODS: The Singapore Chinese Health Study, an ongoing prospective cohort study of 63,257 Chinese Singaporeans. Conditional logistic regression method was used to evaluate these associations with adjustment for potential confounders including the level of education, body mass index, smoking status, alcohol consumption, history of diabetes, serum cotinine and pyridoxal 5'-phosphate, estimated glomerular filtration rate, and total methyl donors (ie, the sum of serum choline, betaine, and methionine). RESULTS: The risk of pancreatic cancer increased with increasing level of serum riboflavin in a dose-dependent manner, especially in men (Ptrend = 0.003). The odds ratio (95% confidence intervals) of pancreatic cancer for the second and third tertiles of serum riboflavin, compared with the lowest tertile, were 9.92 (1.65-59.77) and 25.59 (3.09-212.00), respectively. This positive association was stronger in individuals with a longer follow-up period (≥7 years). CONCLUSIONS: The findings suggest a potential role of riboflavin in the development of pancreatic cancer, especially in men.

Consumption of Coffee, Tea, and Caffeine at Midlife, and the Risk of Physical Frailty in Late Life.

OBJECTIVES: Our study evaluated the prospective association between the consumption of caffeine-containing beverages at midlife and the risk of physical frailty at late life within a population-based cohort of Chinese adults living in Singapore over a follow-up period of 20 years. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: We used data from 12,583 participants from the baseline and third follow-up interviews of the Singapore Chinese Health Study (SCHS). Participants had a mean age of 53 years at baseline (1993-1998), and a mean age of 73 years during the third follow-up (2014-2017). METHODS: At baseline, habitual consumption of caffeine-containing beverages was evaluated using a validated semi-quantitative food-frequency questionnaire. During the third follow-up, physical frailty was assessed using the modified Cardiovascular Health Study phenotype. RESULTS: Compared with non-daily drinkers, those who drank 4 or more cups of coffee daily had reduced odds of physical frailty [odds ratio (OR), 0.54; 95% CI, 0.38-0.76]. Similarly, compared with those who hardly drank tea, participants who drank tea everyday also had reduced odds (OR, 0.82; 95% CI, 0.71-0.95). Total daily caffeine intake at midlife was associated with reduced likelihood of frailty at late life in a dose-response relationship (Ptrend < .001). Relative to their counterparts in the lowest quartile of daily caffeine intake (0-67.6 mg/d), participants in the highest quartile (223.0-910.4 mg/d) had an OR of 0.77 (95% CI, 0.66-0.91). Higher caffeine consumption was associated with lower likelihood of being in the slowest quintile for timed up-and-go (TUG) and weakest quintile for handgrip strength. CONCLUSIONS AND IMPLICATIONS: In this cohort of Chinese adults, higher consumption of caffeine at midlife, via coffee and tea, was associated with a reduced likelihood of physical frailty in late life.

Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools.

BACKGROUND: We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test. METHODS: We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided. RESULTS: The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model. CONCLUSION: Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.

Longitudinal Dietary Trajectories With Cognitive and Psychosocial Well-Being in Chinese Adults Aged 85 Years and Older in Singapore.

Background and Objectives: Studies on longitudinal trajectories of diet and the influence on aging in older adults are limited. We characterized diet quality trajectories over the past 2 decades among adults aged ≥85 years and examined their associations with cognitive and psychosocial outcomes. Research Design and Methods: We used data from 861 participants in the population-based Singapore Chinese Health Study. Dietary intakes were assessed at baseline (mean age [range]: 65 [60-74] years) and at follow-ups 3 (85 [81-95]) and 4 (88 [85-97]) years. Diet quality was measured by adherence to the Dietary Approaches to Stop Hypertension pattern, and group-based trajectory modeling was used to derive diet quality trajectories. At Follow-up 4, we assessed cognition using the Singapore-modified Mini-Mental State Examination, depressive symptoms using the 15-item Geriatric Depression Scale, social engagement, and self-rated health. Multivariable logistic regression models examined associations of diet quality trajectories with these outcomes. Results: About 49.7% had a trajectory with consistently low diet quality scores, whereas 50.3% had a trajectory with consistently high diet quality scores. Compared to the "consistently low" trajectory, the "consistently high" trajectory had 29% and 26% lower likelihoods of cognitive impairment and depressive symptoms, respectively (odds ratio, 95% confidence interval: 0.71 [0.51, 0.99] and 0.74 [0.55, 0.99], respectively); as well as 47% higher likelihood of social engagement (1.47 [1.09, 1.98]). No statistically significant association was observed between the trajectories and self-rated health. Discussion and Implications: Maintaining high diet quality throughout the older adult life course was associated with better cognitive and psychosocial well-being in adults aged ≥85 years.

Evaluation of pre-diagnostic blood protein measurements for predicting survival after lung cancer diagnosis.

BACKGROUND: To evaluate whether circulating proteins are associated with survival after lung cancer diagnosis, and whether they can improve prediction of prognosis. METHODS: We measured up to 1159 proteins in blood samples from 708 participants in 6 cohorts. Samples were collected within 3 years prior to lung cancer diagnosis. We used Cox proportional hazards models to identify proteins associated with overall mortality after lung cancer diagnosis. To evaluate model performance, we used a round-robin approach in which models were fit in 5 cohorts and evaluated in the 6th cohort. Specifically, we fit a model including 5 proteins and clinical parameters and compared its performance with clinical parameters only. FINDINGS: There were 86 proteins nominally associated with mortality (p < 0.05), but only CDCP1 remained statistically significant after accounting for multiple testing (hazard ratio per standard deviation: 1.19, 95% CI: 1.10-1.30, unadjusted p = 0.00004). The external C-index for the protein-based model was 0.63 (95% CI: 0.61-0.66), compared with 0.62 (95% CI: 0.59-0.64) for the model with clinical parameters only. Inclusion of proteins did not provide a statistically significant improvement in discrimination (C-index difference: 0.015, 95% CI: -0.003 to 0.035). INTERPRETATION: Blood proteins measured within 3 years prior to lung cancer diagnosis were not strongly associated with lung cancer survival, nor did they importantly improve prediction of prognosis beyond clinical information. FUNDING: No explicit funding for this study. Authors and data collection supported by the US National Cancer Institute (U19CA203654), INCA (France, 2019-1-TABAC-01), Cancer Research Foundation of Northern Sweden (AMP19-962), and Swedish Department of Health Ministry.

A five-safes approach to a secure and scalable genomics data repository.

Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud. Additionally, regulators are mandating data access patterns and specific security protocols for the storage and use of genomic data. While CSP provides tools for security and regulatory compliance, building the necessary controls required for cloud solutions is not trivial. Research Assets Provisioning and Tracking Online Repository (RAPTOR) by the Genome Institute of Singapore is a cloud-native genomics data repository and analytics platform that implements a "five-safes" framework to provide security and governance controls to data contributors and users, leveraging CSP for sharing and analysis of genomic datasets without the risk of security breaches or running afoul of regulations.

Association between gout at midlife and cognitive impairment at late life - The Singapore Chinese Health Study.

OBJECTIVES: The association between gout and risk of cognitive impairment or dementia is not well established. We examined the relationship between having gout at midlife and the risk of developing cognitive impairment later on. METHODS: We used data of 16,948 participants from the population-based Singapore Chinese Health Study cohort. Participants were recruited from 1993 to 1998 at mean age of 53 years and re-contacted for three follow-up interviews: 1999 to 2004 for follow-up 1, 2006 to 2010 for follow-up 2, and 2014 to 2016 for follow-up 3. History of physician-diagnosed gout was self-reported at follow-up 1 and follow-up 2, while cognitive function was assessed with the Singapore modified Mini-Mental State Examination during follow-up 3, when participants had a mean age of 73.2 years. RESULTS: Gout was reported by 1281 (7.6%) participants at either follow-up 1 or 2, and 2243 (14.4%) had cognitive impairment at follow-up 3. A history of gout was associated with reduced risk of cognitive impairment (OR 0.78, 95% CI 0.65-0.93). This risk was reduced in a stepwise manner with either increased duration of gout or lower age at first diagnosis of gout (Ptrend <0.001). Compared to those without gout, those with gout for ≥20 years (OR 0.56, 95% CI 0.39-0.80) and those with age of onset of gout <50 years old (OR 0.59, 95% CI 0.37-0.94) had a lower risk of developing cognitive impairment. CONCLUSION: A young age of onset or a long history of gout was associated with reduced risk of cognitive impairment in late life.

Low-Carbohydrate Diet Score and the Risk of Colorectal Cancer: Findings from the Singapore Chinese Health Study.

BACKGROUND: Colorectal cancer is common cancer with a high mortality rate. Low-carbohydrate diet (LCD) score holistically evaluates the LCD pattern from carbohydrate, protein, and fat intake. Epidemiologic data of LCD-colorectal cancer association are sparse. METHODS: We evaluated the associations between LCD (i.e., total, animal- and plant-based) and colorectal cancer risk in the Singapore Chinese Health Study, a population-based prospective cohort study including 61,321 Chinese in Singapore who were 45 to 74 years old at baseline. Cox proportional hazard regression model was used to determine the HRs and respective 95% confidence intervals (CI) for colorectal cancer associated with LCD after adjusting for potential confounders, including age, sex, BMI, physical activity, family history of colorectal cancer, etc. RESULTS: After an average of 19.5 years of follow-up, 2,520 participants developed colorectal cancer (1,608 colon cancer and 912 rectal cancer). Overall, the association between total or plant-based LCD scores with the risk of colorectal, colon, or rectal cancer was null (all Ptrend ≥ 0.28). The animal-based LCD was modestly associated with colon cancer risk (Ptrend = 0.02), but not with rectal cancer. Compared with the lowest quartile, HRs (95% CIs) of colon cancer for quartiles 2, 3, and 4 of animal-based LCD were 1.12 (0.98-1.29), 1.27 (1.10-1.46), and 1.14 (0.99-1.31), respectively. CONCLUSIONS: A low-level carbohydrate diet with a high level of animal protein and fat was associated with a moderate increase in the risk of colon cancer among Chinese Singaporeans. IMPACT: High consumption of animal protein/fat and low consumption of carbohydrates may increase colon cancer risk.

Polygenic risk scores for the prediction of common cancers in East Asians: A population-based prospective cohort study.

Background: To evaluate the utility of polygenic risk scores (PRSs) in identifying high-risk individuals, different publicly available PRSs for breast (n=85), prostate (n=37), colorectal (n=22), and lung cancers (n=11) were examined in a prospective study of 21,694 Chinese adults. Methods: We constructed PRS using weights curated in the online PGS Catalog. PRS performance was evaluated by distribution, discrimination, predictive ability, and calibration. Hazard ratios (HR) and corresponding confidence intervals (CI) of the common cancers after 20 years of follow-up were estimated using Cox proportional hazard models for different levels of PRS. Results: A total of 495 breast, 308 prostate, 332 female-colorectal, 409 male-colorectal, 181 female-lung, and 381 male-lung incident cancers were identified. The area under receiver operating characteristic curve for the best-performing site-specific PRS were 0.61 (PGS000873, breast), 0.70 (PGS00662, prostate), 0.65 (PGS000055, female-colorectal), 0.60 (PGS000734, male-colorectal), 0.56 (PGS000721, female-lung), and 0.58 (PGS000070, male-lung), respectively. Compared to the middle quintile, individuals in the highest cancer-specific PRS quintile were 64% more likely to develop cancers of the breast, prostate, and colorectal. For lung cancer, the lowest cancer-specific PRS quintile was associated with 28-34% decreased risk compared to the middle quintile. In contrast, the HR observed for quintiles 4 (female-lung: 0.95 [0.61-1.47]; male-lung: 1.14 [0.82-1.57]) and 5 (female-lung: 0.95 [0.61-1.47]) were not significantly different from that for the middle quintile. Conclusions: Site-specific PRSs can stratify the risk of developing breast, prostate, and colorectal cancers in this East Asian population. Appropriate correction factors may be required to improve calibration. Funding: This work is supported by the National Research Foundation Singapore (NRF-NRFF2017-02), PRECISION Health Research, Singapore (PRECISE) and the Agency for Science, Technology and Research (A*STAR). WP Koh was supported by National Medical Research Council, Singapore (NMRC/CSA/0055/2013). CC Khor was supported by National Research Foundation Singapore (NRF-NRFI2018-01). Rajkumar Dorajoo received a grant from the Agency for Science, Technology and Research Career Development Award (A*STAR CDA - 202D8090), and from Ministry of Health Healthy Longevity Catalyst Award (HLCA20Jan-0022).The Singapore Chinese Health Study was supported by grants from the National Medical Research Council, Singapore (NMRC/CIRG/1456/2016) and the U.S. National Institutes of Health (NIH) (R01 CA144034 and UM1 CA182876).

Although humans contain the same genes, the sequence within these DNA sites can vary from person to person. These small variations, also known as genetic variants, can increase the risk of developing certain diseases. While each variant will only have a weak effect, if multiple variations are present the odds of developing the disease becomes significantly higher. To determine which variants are linked to a disease, researchers carry out genome-wide association studies which involve analyzing the genomes of individuals with and without the condition and comparing their genetic codes. This data is then used to calculate how different combinations of variants impact a person's chance of getting the disease, also known as a polygenic risk score. Currently, most genome-wide association studies only incorporate genetic data from people with European ancestry. Consequently, polygenic risk scores performed using this information may not accurately predict the risk of developing the disease for individuals with other ethnicities, such as people with Asian ancestry. Here, Ho et al. evaluated how well previously calculated polygenic risk scores for the four most common cancers (breast, colorectal, prostate and lung) worked on individuals of East Asian descent. The scores were tested on a dataset containing the genetic sequence, medical history, diet and activity levels of over 21,000 people living in Singapore in the 1990s. Ho et al. found that the polygenic risk scores for breast, prostate and colorectal cancer were able to predict disease risk. However, the score for lung cancer did not perform as well. The polygenic risk score for breast cancer was the most accurate, and was able to stratify individuals into distinct risk bands at an earlier age than other scores. These findings shed light on which existing polygenic risk scores will be effective at assessing cancer risk in individuals with East Asian ancestry. Indeed, Ho et al. have already incorporated the polygenic risk score for breast cancer into a pilot study screening individuals in a comparable population in Singapore. However, the polygenic risk scores tested still performed better on individuals with European ancestry, highlighting the need to address the lack of Asian representation in genome-wide association studies.

Soluble CD137 and risk of hepatocellular carcinoma: nested case-control studies in cohorts in Shanghai and Singapore.

BACKGROUND: The majority of hepatocellular carcinoma (HCC) cases occur in the presence of cirrhosis. Biomarkers of cirrhosis-associated immune dysfunction such as CD8+ T cell cytokines could aid HCC risk assessment. METHODS: CD8+ T cell cytokines were determined in pre-diagnostic serum in two studies including 315 HCC case-control pairs in the Shanghai Cohort Study (SCS) and 197 pairs in the Singapore Chinese Health Study (SCHS). Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for HCC with levels of five cytokines-soluble CD137 (sCD137), soluble Fas (sFas), perforin, macrophage inflammatory protein 1-beta (MIP-1ß), and tumour necrosis factor alpha (TNF-α). RESULTS: sCD137 levels were significantly higher in HCC cases than controls in both cohorts (Ps < 0.001). Compared with the lowest quartile, multivariable-adjusted ORs (95% CI) of HCC for the highest sCD137 quartile were 3.79 (1.73, 8.30) in the SCS and 3.49 (1.44, 8.48) in the SCHS. The sCD137-HCC association was independent of hepatitis B seropositivity and follow-up time. No other cytokine was consistently associated with HCC risk. CONCLUSION: sCD137 was associated with higher risk of HCC in two studies nested in general population cohorts. sCD137 may be a long-term risk marker of HCC development.

Increased BMI and late-life mobility dysfunction; overlap of genetic effects in brain regions.

BACKGROUND: How obesity earlier in life impacts upon mobility dysfunctions in late life is not well understood. Pernicious effects of excess weight on the musculoskeletal system and mobility dysfunctions are well-recognized. However, increasingly more data support the link of obesity to overall motor defects that are regulated in the brain. OBJECTIVES: To assess the causal relationship between body mass index (BMI) at midlife and performance of the Timed Up-and-Go test (TUG) in late life among a population-based longitudinal cohort of Chinese adults living in Singapore. METHODS: We evaluated genetic predispositions for BMI in 8342 participants who were followed up from measurement of BMI at average 53 years, to TUG test (as a functional mobility measure) 20 years later. RESULTS: A robust 75.83% of genetically determined BMI effects on late-life TUG scores were mediated through midlife BMI (Pindirect-effect = 9.24 × 10-21). Utilizing Mendelian randomization, we demonstrated a causal effect between BMI and functional mobility in late life (ßIVW = 0.180, PIVW = 0.001). Secondary gene enrichment evaluations highlighted down-regulation of genes at BMI risk loci that were correlated with poorer functional mobility in the substantia nigra and amygdala regions as compared to all other tissues. These genes also exhibit differential expression patterns during human brain development. CONCLUSIONS: We report a causal effect of obesity on mobility dysfunction. Our findings highlight potential neuronal dysfunctions in regulating predispositions on the causal pathway from obesity to mobility dysfunction.

Adverse cardiovascular and metabolic perturbations among older women: 'fat-craving' hearts.

BACKGROUND: Despite known sex-based differences in cardiovascular aging, differences in aging biology are poorly understood. We hypothesize that circulating metabolites studied cross-sectionally with cardiac aging may be associated with cardiovascular changes that distinguish cardiac aging in women. METHODS: A population-based cohort of community men and women without cardiovascular disease from Singapore underwent detailed clinical and echocardiography examinations. Cross-sectional associations between cardiac functional characteristics and metabolomics profiles were examined. RESULTS: Five hundred sixty-seven adults (48.9% women) participated. Women were younger (72 ± 4.4 years vs 73 ± 4.3 years, p = 0.022), had lower diastolic blood pressures (71 ± 11.0 mmHg vs 76 ± 11.2 mmHg, p < 0.0001, and less likely to have diabetes mellitus (18.0% vs 27.6%, p = 0.013) and smoking (3.8% vs 34.5%, p < 0.001). Body mass indices were similar (24 ± 3.8 kg/m2 vs 24 ± 3.4 kg/m2, p = 0.29), but women had smaller waist circumferences (81 ± 10.1 cm vs 85 ± 9.2 cm, p < 0.001). Women had a significantly higher E/e' ratios (10.9 ± 3.4 vs 9.9 ± 3.3, p = 0.007) and mitral A peak (0.86 ± 0.2 m/s vs 0.79 ± 0.2 m/s, p < 0.001) than men. Among women, lower E/e' ratio was associated with higher levels of C16 (OR 1.019, 95%CI 1.002-1.036, p = 0.029), C16:1 (OR 1.06, 95%CI 1.006-1.118, p = 0.028), serine (OR 1.019, 95%CI 1.002-1.036, p = 0.025), and histidine (OR 1.045, 95%CI 1.013-1.078, p = 0.006). Lower mitral A peak was associated with higher levels of histidine (OR 1.039, 95%CI 1.009-1.070, p = 0.011), isoleucine (OR 1.013, 95%CI 1.004-1.021, p = 0.004), and C20 (OR 1.341, 95%CI 1.067-1.684, p = 0.012). CONCLUSION: Impairments in diastolic functions were more frequent among older women compared to men, despite lower prevalence of vascular risk factors and preserved cardiac structure. Cardiac aging in women correlated with metabolites involved in fatty acid oxidation and tricyclic acid cycle fuelling.

A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium.

Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan-NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation.

Profiles of Successful Aging and Their Association with All-Cause Mortality Risk among the Oldest-Old Chinese in Singapore.

INTRODUCTION: Although successful aging (SA) studies have examined objective indicators such as disease and disability, physical and cognitive function, and social and productive engagement, as well as subjective indicators such as self-rated health, function, and well-being, the interplay among these indicators is rarely studied. We studied SA profiles that captured this interplay and evaluated the association of these profiles with mortality in the oldest-old. METHODS: Respondents were 1,000 Chinese Singaporeans aged ≥85 years during interview visits from 2017 to 2018. Latent class analysis examined 12 objective and subjective indicators to identify SA profiles. Multivariable Cox regression assessed the relationship between these profiles and all-cause mortality risk through 2020. RESULTS: Four distinct SA profiles were identified: "frail and dejected" (poor performance in nearly all objective and subjective indicators), "frail but resilient" (poor in objective but good in subjective indicators), "fairly fit and neutral" (good in about half of the indicators), and "fit and positive" (good in nearly all indicators). Compared with "frail and dejected," the adjusted hazard ratio (95% confidence interval) for mortality risk was 0.63 (0.40-0.97) in "frail but resilient," 0.56 (0.34-0.93) in "fairly fit and neutral," and 0.31 (0.19-0.49) in "fit and positive." DISCUSSION: SA in the oldest-old could take different profiles based on objective and subjective indicators, and these profiles have implications for mortality risk. Individuals with good subjective indicators have advantage in survival despite poor objective indicators.

Epstein-Barr Virus Glycoprotein Antibody Titers and Risk of Nasopharyngeal Carcinoma.

We evaluated antibody against Epstein-Barr virus glycoproteins (gp350, gH/gL, gB, gp42) in 97 nasopharyngeal carcinoma (NPC) cases and 97 cancer-free controls. Each unit increase in log-transformed antibody against gp350 and gH/gL was associated with 2.27 (95% confidence interval [CI], 1.20-4.29) and 2.18 (95% CI, 1.22-3.90) higher odds of NPC, respectively. This association was more apparent for NPC diagnosed within 5 years of antibody measurement.

Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program.

The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize low-dose CT (LDCT) lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1161 proteins in a nested-case control study within 2 prospective cohorts (n = 252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n = 479 cases and 479 controls). Eligible participants had a current or former history of smoking and cases were diagnosed up to 3 years following blood draw. The Nodule Malignancy project measured 1078 proteins among participants with a heavy smoking history within four LDCT screening studies (n = 425 cases diagnosed up to 5 years following blood draw, 430 benign-nodule controls, and 398 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n = 1696 cases and 2926 subcohort representatives), and in the Nodule Malignancy project within five LDCT screening studies (n = 675 cases, 680 benign-nodule controls, and 648 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.

Dietary Nonstarch Polysaccharide Intake and Risk of Colorectal Cancer: Findings from the Singapore Chinese Health Study.

Dietary fiber or non-starch polysaccharides (NSP) may provide protection from CRC development. Epidemiologic studies on the association between dietary fiber and CRC is inconsistent are limited on NSP as a modifiable risk factor. Using the Singapore Chinese Health Study, a population-based prospective cohort of 61,321 cancer-free middle-aged or older Chinese Singaporeans, we examined the association between dietary fiber and NSP intakes and CRC risk. Fiber and NSP intakes at baseline were obtained using a validated semi-quantitative food frequency questionnaire coupled with the Singapore Food Composition Database. Cox proportional hazard regression model was used to estimate the hazard ratios (HRs) and respective 95% confidence intervals (CIs) for CRC associated with dietary fiber and NSP intakes after adjusting for potential confounders. After an average of 17.5 years of follow-up, 2,140 participants developed CRC. NSP was inversely associated with the risk of CRC in a dose-dependent manner whereas dietary fiber was not associated with risk of CRC overall or histologic subtypes. The multivariable-adjusted HRs (95% CIs) of CRC for quartiles 2, 3 and 4 of dietary NSP intake were 0.99 (0.88-1.11), 0.98 (0.87-1.11) and 0.84 (0.73-0.95), respectively, compared with the lowest quartile (P trend =0.006). This inverse association was more apparent for colon cancer (HRQ4 vs. Q1=0.79, 95% CI: 0.67-0.93, P trend =0.003) than rectal cancer (HR Q4 vs. Q1=0.92, 95% CI: 0.74-1.13, P trend =0.53). Our findings suggested that dietary NSP but not fiber is associated with a reduced risk of colon cancer in Chinese Singaporeans. Significance: Non-starch polysaccharides may be beneficial for colorectal cancer primary prevention.