Changing global epidemiology of chronic hepatitis C virus-related outcomes from 2010 to 2019: cirrhosis is the growing burden of hepatitis C virus-related disease.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) has a long-term impact on hepatic consequences. A comprehensive evaluation of the global burden of HCV-related health outcomes can help to develop a global HCV prevention and treatment program. METHODS: We used the 2019 Global Burden of Disease (GBD) Study to comprehensively investigate burden and temporal trends in incidence, mortality and disability-adjusted life-years (DALYs) of HCV-related diseases, including liver cancer and cirrhosis and other liver diseases across 264 countries and territories from 2010 to 2019. RESULTS: Globally, there were 152 225 incident cases, 141 811 deaths and approximately 2.9 million DALYs because of HCV-related liver cancer, and 551 668 incident cases, 395 022 deaths and about 12.2 million DALYs because of HCV-related cirrhosis in 2019. Worldwide, during the 2010-2019 period, liver cancer incidence declined, however, there was a 62% increase in cirrhosis incidence. In 2019, the Eastern Mediterranean was the region with the highest rates of incidence and mortality of both liver cancer and cirrhosis. Africa was the region with the fastest-growing trend of incidence of cirrhosis in the 2010-2019 period [annual percentage change (APC) = 2.09, 95% confidence interval (CI): 1.93-2.25], followed by the Western Pacific region (APC = 1.17, 95% CI: 1.09-1.22). Americas were the only region observing increased trends in liver cancer and cirrhosis mortality (APC = 0.70 and 0.12, respectively). We identified three patterns of temporal trends of mortality rates of liver cancer and cirrhosis in countries that reported HCV treatment rates. CONCLUSION: Urgent measures are required for diagnosis, treatment and research on HCV-related cirrhosis at global, regional and country levels, particularly in Africa, the Western Pacific and the Eastern Mediterranean.

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

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. A nested case-control study involved 197 HCC cases and 465 controls was also constructed among 28,346 participants who provided blood samples. Cox proportional hazard regression method was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HCC with different levels of LCD scores. Conditional logistic regression was performed for the case-control study analysis. After 17.6 years of follow-up with 819,573 person-years, 561 participants developed primary HCC. Although there was a null association between total LCD score and HCC risk (HRper-SD increment=1.07, 95% CI: 0.98-1.16; P-trend=0.06), there was a positive association between animal-based LCD and the risk of HCC (HRper-SD increment=1.11, 95% CI: 1.02-1.21; Ptrend=0.01). Furthermore, this association was present in both HBsAg-negative and HBsAg-positive individuals in the case-control study. In stratified analysis for the entire cohort, this positive association was only present in those who consumed alcoholic beverages monthly or less frequent but not in weekly or daily drinker (Pinteraction=0.79). In summary, a diet with lower carbohydrate, higher animal fat and protein was significantly associated with higher risk of HCC among Chinese Singaporeans.

Tryptophan intake and pancreatic cancer: findings from a case-control study.

BACKGROUND: Pancreatic cancer is a leading cause of cancer-related death worldwide. Tryptophan plays a vital role in cell growth and maintenance as a building block of protein and coordination of organismal responses to environmental and dietary cues. Animal model study showed that dietary tryptophan improved treatment response in those who received chemotherapy or immune checkpoint inhibitors. Limited data are available assessing the association between tryptophan intake and risk of pancreatic cancer. We aimed to evaluate this association in a case-control study in Vietnam. METHODS: We analyzed data from a case-control study, including 3759 cancer cases and 2995 control subjects of whom 37 with pancreatic cancer cases. Tryptophan intake was derived from food frequency questionnaire. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for different levels of tryptophan intake with pancreatic cancer risk. RESULTS: Overall, tryptophan intake was inversely associated with pancreatic cancer risk in a dose-dependent manner. The ORs and 95% CIs of pancreatic cancer were 0.51 (0.29-0.92) for continuous scale, 0.27 (0.10-0.73) for tertile 2 and 0.34 (0.11-1.06) for tertile 3, compared with tertile 1 (the lowest intake) (Ptrend = 0.02). In stratified analysis, this inverse association pattern was present among those with BMI < 23 kg/m2 and ever drinkers. CONCLUSION: A diet with a higher intake of tryptophan was significantly associated with a lower incidence of pancreatic cancer among Vietnamese population. These suggest that dietary modification may be an effective strategy for primary prevention of pancreatic cancer development.

Clinicopathologic Characteristics of Thyroid Microcarcinoma: Findings from a Hospital-Based Study in Vietnam.

BACKGROUND: Thyroid microcarcinoma (TMC) incidence has significantly increased in recent decades. The rates of lymph node metastasis extrathyroidal extension have been significantly different in patients with TMC ≤5 mm versus those with size >5 mm. The current analysis aimed to examine the clinicopathologic features of TMC measuring <5 mm and to compare them with those of TMC ≥5 mm. METHODS: A total of 273 patients with TMC confirmed by histological examination from December 2020 to May 2021 were enrolled in Bach Mai Hospital, Hanoi, Vietnam. Unconditional logistic regression models were used to determine the association between clinicopathological factors and tumor size, central lymph node metastasis and extrathyroidal extension. RESULTS: We found 212/273 patients (77.7%) were diagnosed incidentally. The majority of patients were female (87.5%) and had a mean age of 44.2 years. The mean tumor size (±standard deviation (SD)) was 5.72 ± 2.33 mm. Most of the patients were also diagnosed with papillary TMC. Multifocal and bilateral lesions accounted for 13.2% and 12.1%, respectively. The extrathyroidal invasion was observed in 14.7% (40 patients), while 24.5% (67 patients) were those with central lymph node metastases. The rate of extrathyroidal extension in patients with tumor size ≥5 mm was significantly higher than in patients with tumor size <5 mm (odds ratio (OR) = 4.98; 95% confidence interval (CI): 1.48-16.70; p = 0.004). Patients with body mass index (BMI) <23 kg/m2 were found to be protected against the odds of extrathyroidal extension (OR = 0.38, 95% CI: 0.19-0.75; p = 0.004) compared to those with BMI ≥23 kg/m2. In univariable mode, central lymph node metastasis was positively associated with the odds of the presence of extrathyroidal extension (OR = 2.70, 95% CI: 1.34-5.45; p = 0.004). In the multivariable model, central lymph node metastasis was also associated with the presence of extrathyroidal extension (OR = 2.507, 95% CI: 1.194-5.264; p = 0.017). Univariate analysis demonstrated that tumor size ≥5 mm (OR = 2.04; 95% CI: 1.01-4.17; p = 0.047) and extrathyroidal extension (OR = 2.71; 95% CI: 1.34-5.45; p = 0.004) were risk factors of central cervical lymph node metastasis. In multivariable models, the extrathyroidal extension was associated with central lymph metastasis. CONCLUSIONS: TMC <5 mm tumor size is less likely to have aggressive characteristics, including extrathyroidal extension, than a TMC ≥5 mm. Long-term follow-up studies are thus warranted to investigate the factors in the prognosis of TMC.

Household food insecurity during the COVID-19 pandemic and associated socioeconomic demographic factors in Papua New Guinea: evidence from the Comprehensive Health and Epidemiological Surveillance System.

INTRODUCTION: The COVID-19 pandemic had an unprecedented impact on global food security, but little is known about the impact on food security at the household level. We examined the prevalence and socioeconomic demographic factors for household food insecurity during the COVID-19 pandemic in Papua New Guinea. METHODS: Household socioeconomic demographic data from the Comprehensive Health and Epidemiological Surveillance System were collected from six main provinces in 2020 (37880 participants) and compared with the 2018 data (5749 participants). The prevalence of household food insecurity was estimated and stratified by household socioeconomic demographic characteristics. Multinomial logistic regression was conducted to estimate adjusted OR (aOR) and 95% CI of risk factors. RESULTS: The overall prevalence of household food insecurity increased from 11% in 2018 to 20% in 2020, but varied across provinces, with the highest level reported in Central Province (35%) and the lowest level in East New Britain Province (5%).Food shortages were 72% less likely among urban residents than those living in rural areas (aOR 0.28 (95% CI 0.21 to 0.36)). The risk of food insecurity was 53% higher among adults aged 25+ years with primary education (grades 3-8) than those with university education (aOR 1.53 (95% CI 1.09 to 2.13)). People from households in the poorest wealth quintiles were 80% more likely to report food shortage than those from the richest wealth quintile (aOR 1.78 (95% CI 1.29 to 2.45). CONCLUSION: The study provides evidence to develop policy and intervention to deal with food insecurity in emergency situations in the future.

A robust platform for integrative spatial multi-omics analysis to map immune responses to SARS-CoV-2 infection in lung tissues.

The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid and similar, but a robust platform for deep tissue characterization of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues. Five tissue-profiling technologies were combined by a novel computational mapping methodology to comprehensively characterize and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi-omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS-CoV-2 on the lungs.

Patterns in Cancer Incidence Among People Younger Than 50 Years in the US, 2010 to 2019.

Importance: Emerging data suggest that the incidence of early-onset cancers, defined as cancers diagnosed in people younger than 50 years, is increasing, but updated data are limited. Objective: To characterize the patterns in the incidence of early-onset cancers in the US from 2010 to 2019 and provide granular data on the cancers with the fastest-growing incidence rates. Design, Setting, and Participants: This population-based cohort study analyzed data from 17 National Cancer Institute Surveillance, Epidemiology, and End Results registries from January 1, 2010, to December 31, 2019. Age-standardized incidence rates per 100 000 people were extracted for early-onset cancers, with rates age adjusted to the US standard population. A total of 562 145 patients with early-onset cancer between 2010 and 2019 were identified and included. Data were analyzed from October 16, 2022, to May 23, 2023. Main Outcomes and Measures: Primary outcomes were incidence rates and descriptive epidemiological data for people younger than 50 years with cancer. The annual percentage change (APC) of the age-standardized incidence rate was estimated using the Joinpoint regression program. Results: Among 562 145 patients (324 138 [57.7%] aged 40-49 years; 351 120 [62.5%] female) with early-onset cancer, 4565 (0.8%) were American Indian or Alaska Native, 54 876 (9.8%) were Asian or Pacific Islander, 61 048 (10.9%) were Black, 118 099 (21.0%) were Hispanic, 314 610 (56.0%) were White, and 8947 (1.6%) were of unknown race and/or ethnicity. From 2010 to 2019, the age-standardized incidence rate of early-onset cancers increased overall (APC, 0.28%; 95% CI, 0.09%-0.47%; P = .01) and in female individuals (APC, 0.67%; 95% CI, 0.39%-0.94%; P = .001) but decreased in male individuals (APC, -0.37%; 95% CI, -0.51% to -0.22%; P < .001). In contrast, the age-standardized incidence rate of cancers in individuals aged 50 years and older decreased over the study period (APC, -0.87%; 95% CI, -1.06% to -0.67%; P < .001). In 2019, the highest number of incident cases of early-onset cancer were in the breast (n = 12 649). From 2010 to 2019, gastrointestinal cancers had the fastest-growing incidence rates among all early-onset cancer groups (APC, 2.16%; 95% CI, 1.66%-2.67%; P < .001). Among gastrointestinal cancers, those with the fastest-growing incidence rates were in the appendix (APC, 15.61%; 95% CI, 9.21%-22.38%; P < .001), intrahepatic bile duct (APC, 8.12%; 95% CI, 4.94%-11.39%; P < .001), and pancreas (APC, 2.53%; 95% CI, 1.69%-3.38%; P < .001). Conclusions and Relevance: In this cohort study, the incidence rates of early-onset cancer increased from 2010 to 2019. Although breast cancer had the highest number of incident cases, gastrointestinal cancers had the fastest-growing incidence rates among all early-onset cancers. These data may be useful for the development of surveillance strategies and funding priorities.

Incidence of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis or advanced liver fibrosis.

BACKGROUND: HCC can develop in the absence of cirrhosis in patients with NAFLD. We aimed to estimate the incidence of HCC in patients with NAFLD with and without cirrhosis or advanced liver fibrosis. METHODS: We performed a cohort study to determine the incidence of HCC in patients with NAFLD identified by the International Classification of Diseases 9/10 codes in the electronic health records of a US health care system between 2004 and 2018. The incidence of HCC was stratified by the presence or absence of cirrhosis and by the Fibrosis-4 index (FIB-4) at the time of HCC diagnosis. RESULTS: Of 47,165 patients with NAFLD aged 40-89 years, 981 (2.1%) developed HCC (mean follow-up 3.4 y). Among patients with HCC, 842 (85.8%) had cirrhosis, while 139 (14.2%) did not. Of the 139 patients with HCC without cirrhosis-related diagnostic codes, 26 (2.7%) had FIB-4 >2.67 (advanced fibrosis likely), whereas 43 (4.4%) had FIB-4 < 1.30 (excluding advanced fibrosis). The annual incidence of HCC in patients with NAFLD with and without cirrhosis was 23.6 and 1.1 per 1000 person-years, respectively. Among patients without cirrhosis, the annual incidence of HCC was 2.8 per 1000 person-years with FIB-4 >2.67 and 0.7 per 1000 person-years with FIB-4 <1.30. Patients with NAFLD and cirrhosis were 31.8 times (95% CI, 23.3-43.4) more likely to develop HCC than those without cirrhosis and FIB-4 <1.30, after adjustment for age and sex. CONCLUSIONS: Patients with NAFLD without cirrhosis nor advanced fibrosis have a low incidence of HCC.

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.

Associations between Ileal Juice Bile Acids and Colorectal Advanced Adenoma.

BACKGROUND: There is an urgent need to identify biomarkers for advanced adenoma, an important precursor of colorectal cancer (CRC). We aimed to determine alterations in ileal juice bile acids associated with colorectal advanced adenoma. METHODS: We quantified a comprehensive panel of primary and secondary bile acids and their conjugates using an ultraperformance liquid chromatography triple-quadrupole mass spectrometric assay in ileal juice collected at colonoscopy from 46 study subjects (i.e., 14 biopsy-confirmed advanced adenomas and 32 controls free of adenoma or cancer). Using analysis of covariance (ANCOVA), we examined the differences in bile acid concentrations by disease status, adjusting for age, sex, body mass index, smoking status and type 2 diabetes. RESULTS: The concentrations of hyodeoxycholic acid (HCA) species in ileal juice of the advanced adenoma patients (geometric mean = 4501.9 nM) were significantly higher than those of controls (geometric mean = 1292.3 nM, p = 0.001). The relative abundance of ursodeoxycholic acid (UDCA) in total bile acids was significantly reduced in cases than controls (0.73% in cases vs. 1.33% in controls; p = 0.046). No significant difference between cases and controls was observed for concentrations of total or specific primary bile acids (i.e., cholic acid (CA), chenodeoxycholic acid (CDCA) and their glycine- and taurine-conjugates) and total and specific major secondary bile acids (i.e., deoxycholic acid and lithocholic acid). CONCLUSIONS: Colorectal advanced adenoma was associated with altered bile acids in ileal juice. The HCA species may promote the development of colorectal advanced adenoma, whereas gut microbiota responsible for the conversion of CDCA to UDCA may protect against it. Our findings have important implications for the use of bile acids as biomarkers in early detection of colorectal cancer.

A call for standardized reporting of early-onset colorectal peritoneal metastases.

BACKGROUND: The incidence of colorectal cancer (CRC) in patients under 50 years of age, i.e., early-onset CRC, has increased in the past two decades. Colorectal peritoneal metastases (CPM) will develop in 10-30% of CRC patients. CPM traditionally had a dismal prognosis, but surgery and novel systemic treatments appear to increase survival. Determining potential age-associated risk and prognostic factors is optimized when analyses use standardized age groupings. METHODS: We performed a review of early-onset CPM studies and compared variables used, e.g., age stratification and definitions of synchronous and metachronous CPM. We included studies published in PubMed up to November 2022 if results were stratified by age. RESULTS: Of 114 screened publications in English, only 10 retrospective studies met inclusion criteria. Incidence of CPM was higher in younger CRC patients (e.g. 23% vs. 2% for <25 vs. ≥25 years, P < 0.0001; and 57% vs. 39% vs. 4% for <20 vs. 20-25 vs. >25 years, P < 0.001); two studies reported higher proportion of younger African American CPM patients (e.g. 16% vs. 6% for <50 vs. ≥50 years). Studies used seven different age-stratification methods, presenting comparison challenges. CONCLUSION: Studies showed a higher proportion of CPM in younger patients, but directly comparing results was not possible due to inconsistent reporting. To better address this issue, CRC and CPM studies stratified by standard age groups (e.g. <50 vs. ≥50) are needed.

Association between Sleep Duration and Colorectal Adenomas: Findings from a Case-Control Study in Vietnam.

BACKGROUND: Colorectal cancer is one of the leading cancers worldwide and in Vietnam. Adenomas are important precursors of colorectal cancer. Study on the association between sleep duration and development of colorectal adenoma (CRA) is limited, particularly among Vietnamese population. METHODS: We conducted an individually matched case-control study of 870 CRA cases and 870 controls in a large-scale colorectal screening program involving 103,542 individuals ages ≥40 years old in Hanoi, Vietnam. Sleep duration was categorized in three groups: short: ≤6 hours/day, normal: 7 to 8 hours/day, and long: >8 hours/day. Conditional logistic regression was used to evaluate the association between sleep duration and adenomas risk after controlling for potential confounders. RESULTS: Overall, short-sleep duration was associated with increased risk of having CRA compared with normal duration [OR, 1.48; 95% confidence interval (CI), 1.12-1.97]. This pattern was present in both females (OR, 1.58; 95% CI, 1.14-2.18) and males (OR, 1.45; 95% CI, 1.08-1.93), with advanced adenomas (OR, 1.61; 95% CI, 1.09-2.38) and non-advanced adenomas (OR, 1.66; 95% CI, 1.19-2.32). Furthermore, the association between CRA development and short-sleep duration was more apparent among females who were nondrinker, nonobese, physically active, with proximal or both sided adenomas and with cardiometabolic disorder. Among males, the short-sleep duration was associated with CRA risk among never-smoking, cardiometabolic disorders, and obese. CONCLUSIONS: Short-sleep duration was associated with increased prevalence of both advanced and non-advanced CRAs among Vietnamese population. IMPACT: Findings from this study showed that maintaining an adequate sleep duration may have an important implication for colorectal adenoma prevention and control.

High serum magnesium is associated with lower risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major contributor to the rising incidence of hepatocellular carcinoma (HCC). Magnesium is a major cation in cellular activities. Epidemiological data on magnesium level and its relation to HCC are sparse. This study aimed to examine the associations between serum levels of magnesium and the risk of HCC among patients with NAFLD. METHODS: A total of 26,053 patients with NAFLD were identified in the University of Pittsburgh Medical Center Electronic Health Records from 2004 through 2018. After an average of 5.15 years of follow-up, 395 patients developed HCC after the first measurement of serum magnesium. Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% CIs of HCC incidence associated with quartile levels of serum magnesium after adjustment for age, sex, race, body mass index, diuretics use, history of type 2 diabetes, history of hypertension, history of hyperlipidemia, and tobacco smoking. RESULTS: Patients with NAFLD who developed HCC had a significantly lower mean (± standard deviation) serum magnesium (0.769 ± 0.131 mmol/L) than those who remained free of HCC (0.789 ± 0.125 mmol/L; p = .003). Compared with the lowest quartile, the HRs (95% CIs) of HCC second, third, and fourth quartiles of serum magnesium were 0.87 (0.67-1.12), 0.77 (0.57-1.04), and 0.73 (0.56-0.96), respectively, after adjustment for multiple potential confounders (P trend  = .02). CONCLUSION: This finding suggests higher levels of serum magnesium were significantly associated with decreased risk of HCC among patients with NAFLD.

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.

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.

Neutrophil-lymphocyte ratio in relation to risk of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease.

BACKGROUND: Blood neutrophil to lymphocyte ratio (NLR) or lymphocyte count may be important markers for immune function. Previous work has shown higher NLR was associated with higher risk of hepatitis B-related hepatocellular carcinoma (HCC). However, studies in non-alcoholic fatty liver disease (NAFLD) patients are lacking. METHODS: Utilizing the University of Pittsburgh Medical Center (UPMC) electronic health records, we created a retrospective cohort of 27,834 patients diagnosed with NAFLD from 2004 to 2018 with complete NLR data. After an average 5.5 years of follow-up, 203 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence associated with different levels of NLR and lymphocyte count. RESULTS: Compared with the lowest tertile of NLR (<1.97), the highest tertile of NLR (≥3.09) was statistically significantly associated with a 43% higher risk of HCC incidence (HR = 1.43, 95% CI: 1.01-2.03, ptrend  = 0.031) after adjustment for age, sex, race, body mass index, smoking status, history of type 2 diabetes, hyperlipidemia, hypertension, and fibrosis-4 score category. Conversely the highest tertile of lymphocyte count (≥2.15 K/ul) was significantly associated with a 36% lower risk of HCC (HR = 0.64, 95% CI: 0.43-0.94, ptrend  = 0.028) compared to the lowest tertile (<1.55 K/ul). There was no association between neutrophil count and HCC risk. CONCLUSIONS: Higher NLR and lower lymphocyte count are associated with significantly higher risk of HCC among NAFLD patients. These findings warrant further investigation of immune response and surveillance in association with HCC development in NAFLD patients.

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.

The Association between Peptic Ulcer Disease and Gastric Cancer: Results from the Stomach Cancer Pooling (StoP) Project Consortium.

BACKGROUND: Gastric cancer (GC) is the fifth most common type of cancer and the fourth most common cause of cancer-related mortality. Although the risk of GC and peptic ulcer disease (PUD) is known to be increased by H. pylori infection, evidence regarding the direct relationship between PUD and GC across ethnicities is inconclusive. Therefore, we investigated the association between PUD and GC in the Stomach cancer Pooling (StoP) consortium. METHODS: History of peptic ulcer disease was collected using a structured questionnaire in 11 studies in the StoP consortium, including 4106 GC cases and 6922 controls. The two-stage individual-participant data meta-analysis approach was adopted to generate a priori. Unconditional logistic regression and Firth's penalized maximum likelihood estimator were used to calculate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between gastric ulcer (GU)/duodenal ulcer (DU) and risk of GC. RESULTS: History of GU and DU was thoroughly reported and used in association analysis, respectively, by 487 cases (12.5%) and 276 controls (4.1%), and 253 cases (7.8%) and 318 controls (6.0%). We found that GU was associated with an increased risk of GC (OR = 3.04, 95% CI: 2.07-4.49). No association between DU and GC risk was observed (OR = 1.03, 95% CI: 0.77-1.39). CONCLUSIONS: In the pooled analysis of 11 case-control studies in a large consortium (i.e., the Stomach cancer Pooling (StoP) consortium), we found a positive association between GU and risk of GC and no association between DU and GC risk.

The Association between Serum Serine and Glycine and Related-Metabolites with Pancreatic Cancer in a Prospective Cohort Study.

Background. Serine and glycine play an important role in the folate-dependent one-carbon metabolism. The metabolism of serine and glycine has been shown to be associated with cancer cell proliferation. No prior epidemiologic study has investigated the associations for serum levels of serine and glycine with pancreatic cancer risk. Methods. We conducted a nested case-control study involved 129 incident pancreatic cancer cases and 258 individually matched controls within a prospective cohort study of 18,244 male residents in Shanghai, China. Glycine and serine and related metabolites in pre-diagnostic serum were quantified using gas chromatography-tandem mass spectrometry. A conditional logistic regression method was used to evaluate the associations for serine, glycine, and related metabolites with pancreatic cancer risk with adjustment for potential confounders. Results: Odds ratios (95% confidence intervals) of pancreatic cancer for the highest quartile of serine and glycine were 0.33 (0.14−0.75) and 0.25 (0.11−0.58), respectively, compared with their respective lowest quartiles (both p's < 0.01). No significant association with risk of pancreatic cancer was observed for other serine- or glycine related metabolites including cystathionine, cysteine, and sarcosine. Conclusion. The risk of pancreatic cancer was reduced by more than 70% in individuals with elevated levels of glycine and serine in serum collected, on average, more than 10 years prior to cancer diagnosis in a prospectively designed case-control study. These novel findings support a protective role of serine and glycine against the development of pancreatic cancer in humans that might have an implication for cancer prevention.

NAFLD polygenic risk score and risk of hepatocellular carcinoma in an East Asian population.

It is difficult to identify people with nonalcoholic fatty liver disease (NAFLD) who are at high risk for developing hepatocellular carcinoma (HCC). A polygenic risk score (PRS) for hepatic fat (HFC-PRS) derived from non-Asians has been reported to be associated with HCC risk in European populations. However, population-level data of this risk in Asian populations are lacking. Utilizing resources from 24,333 participants of the Singapore Chinese Health Study (SCHS), we examined the relationship between the HFC-PRS and HCC risk. In addition, we constructed and evaluated a NAFLD-related PRS (NAFLD-PRS) with HCC risk in the SCHS. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence with both HFC-PRS and NAFLD-PRS. The HFC-PRS and NAFLD-PRS were highly correlated (Spearman r = 0.79, p < 0.001). The highest quartiles of both the HFC-PRS and the NAFLD-PRS were associated with significantly increased risk of HCC with HR of 2.39 (95% CI 1.51, 3.78) and 1.77 (95% CI 1.15, 2.73), respectively, compared with their respective lowest quartile. Conclusion: The PRS for hepatic fat content or NAFLD may be useful for assessing HCC risk in both Asian and European populations. The findings of this and prior studies support a potential causal role of genetically determined NAFLD in HCC development.