Association of gut microbiome with immune microenvironment in surgically treated colorectal cancer patients.

This study explored the relationship between faecal microbiota distribution and local or systemic immune response in patients with colorectal cancer (CRC). The study population included 114 surgically treated CRC patients. Faeces were analysed using 16S rRNA gene sequencing. The immune score in tumour microenvironment was evaluated using CD3 and CD8 immunohistochemistry. Genetic alterations, microsatellite instability status and five systemic inflammatory markers were also analysed. Thirty of 114 (26.3%) CRC patients were categorised as the 'immune type' with a high density of T-cells. The immune type CRC cases showed lower angiolymphatic invasion and longer overall survival. Of the 123 selected bacterial species, Bacteroides fragilis and Collinsella aerofaciens were prevalent in immune CRC cases, whereas Odoribacter splanchnicus and Phascolarctobacterium succinatutens were prevalent in non-immune CRC patients. Bacteroides fragilis was associated with shorter disease free survival in univariable and multivariable survival analyses. Regarding systemic immunity, a high prevalence of C. aerofaciens was associated with a high modified Glasgow prognostic score. This study revealed a potential relationship among the gut microbiome, immune microenvironment, and disease progression in patients with CRC. Our findings suggest that abundant B. fragilis in patients with CRC is associated with a 'cold immune' tumour microenvironment.

User tendency-based rating scaling in online trading networks.

Social networks often involve the users rating each other based on their beliefs, abilities, and other characteristics. This is particularly common in e-commerce platforms where buyers rate sellers based on their trustworthiness. However, the rating tends to vary between users due to differences in their individual scoring criteria. For example, in a transaction network, a positive user may give a high rating unless the transaction was unsatisfactory while a neutral user may give a mid-rating, consequently giving the same numeric score to different levels of satisfaction. In this paper, we propose a novel method called user tendency-based rating scaling, which adjusts the current rating (its score) based on the pattern of past ratings. We investigate whether this rating scaling method can classify between "good users" and "bad users" in online trade social networks better when compared with using the original rating scores without scaling. Classifying between good users and bad users is especially important for anonymous rating networks like Bitcoin transaction networks, where users' reputations must be recorded to preclude fraudulent and risky users. We evaluate the proposed rating scaling method by performing user classification, link prediction, and clustering tasks, using three real-world online rating network datasets. We use both the original ratings and the scaled ratings as weights of graphs and use a weighted graph embedding method to find node representations that reflect users' positive and negative information. The experimental results showed that using the proposed rating scaling method outperformed using the original (i.e., unscaled) ratings by up to 17% in classification accuracy, and by up to 2.5% in link prediction based on the AUC ROC measure, and by up to 21% in the clustering tasks based on the Dunn-index.

Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants.

BACKGROUND: The family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case-control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study. METHODS: We included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium. Cox proportional hazard regression was used to estimate study-specific adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between family history of gastric cancer and gastric cancer incidence and mortality, then pooled using random-effects meta-analyses. Stratified analyses were performed for the anatomical subsites and histological subtypes. RESULTS: During the mean follow-up of 15.6 years, 2258 incident gastric cancers and 5194 gastric cancer deaths occurred. The risk of incident gastric cancer was higher in individuals with a family history of gastric cancer (HR 1.44, 95% CI 1.32-1.58), similarly in males (1.44, 1.31-1.59) and females (1.45, 1.23-1.70). Family history of gastric cancer was associated with both cardia (HR 1.26, 95% CI 1.00-1.60) and non-cardia subsites (1.49, 1.35-1.65), and with intestinal- (1.48, 1.30-1.70) and diffuse-type (1.59, 1.35-1.87) gastric cancer incidence. Positive associations were also found for gastric cancer mortality (HR 1.30, 95% CI 1.19-1.41). CONCLUSIONS: In this largest prospective study to date on family history and gastric cancer, a familial background of gastric cancer increased the risk of gastric cancer in the Asian population. Targeted education, screening, and intervention in these high-risk groups may reduce the burden of gastric cancer.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.

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. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

The Association of Low-Carbohydrate Diet and HECTD4 rs11066280 Polymorphism with Risk of Colorectal Cancer: A Case-Control Study in Korea.

Background: Glucose is a main source of energy for tumor cells. Thus, a low-carbohydrate diet (LCD) is thought to make a significant contribution to cancer prevention. In addition, LCD and HECT domain E3 ubiquitin protein ligase 4 (HECTD4) gene may be related to insulin resistance. Objectives: We explored whether LCD score and HECTD4 rs11066280 are etiological factors for colorectal cancer (CRC) and whether LCD score interacts with HECTD4 rs11066280 to modify CRC risk. Methods: We included 1457 controls and 1062 cases in a case-control study. The LCD score was computed based on the proportion of energy obtained from carbohydrate, protein, and fat, as determined by a semiquantitative food frequency questionnaire. We used unconditional logistic regression models to explore the association of HECTD4 with CRC prevention and interaction of LCD score and HECTD4 polymorphism with CRC preventability. Results: Individuals with AA/AT genotypes who carried a minor allele (A) of HECTD4 rs11066280 exhibited a decreased CRC risk [odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.62, 0.91]. In addition, a protective effect of high LCD score against CRC development was identified (OR = 0.52, 95% CI: 0.40, 0.68, P for trend <0.001). However, the effect of LCD depended on individual's genetic background, which appears only in participants with TT genotype of HECTD4 rs11066280 [OR = 0.49 (0.36-0.68), P interaction = 0.044]. Conclusions: Our findings suggest a protective effect of LCD and a minor allele of HECTD4 rs11066280 against CRC development. In addition, we provide an understanding of the interaction effect of LCD and HECTD4 rs11066280 on CRC, which may be helpful for establishing diet plans regarding cancer prevention.

Interactions between vitamin B2, the MTRR rs1801394 and MTR rs1805087 genetic polymorphisms, and colorectal cancer risk in a Korean population.

Objectives: We explored whether the association between vitamin B2 and colorectal cancer (CRC) risk could be modified by the MTRR rs1801394 and MTR rs1805087 genetic polymorphisms and examined whether the interaction effects are sex-specific. Methods: We performed a case‒control study involving 1,420 CRC patients and 2,840 controls from the Korea National Cancer Center. Dietary vitamin B2 intake was assessed using a semiquantitative food frequency questionnaire, and the association with CRC was evaluated. Genotyping was performed using an Illumina MEGA-Expanded Array. For gene-nutrient interaction analysis, pre-matched (1,081 patients and 2,025 controls) and matched (1,081 patients and 1,081 controls) subsets were included. Unconditional and conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: A higher intake of vitamin B2 was associated with a significantly lower CRC risk (OR=0.65; 95% CI, 0.51-0.82; p<0.001). Carriers of at least 1 minor allele of MTRR rs1801394 showed a significantly higher CRC risk (OR=1.43; 95% CI, 1.12-1.83). Men homozygous for the major allele (A) of MTRR rs1801394 and who had a higher intake of vitamin B2 had a significantly lower CRC risk (OR=0.31; 95% CI, 0.18-0.54; p-interaction=0.02). In MTR rs1805087, men homozygous for the major allele (A) and who had a higher vitamin B2 intake had a significantly lower CRC risk (OR=0.38; 95% CI, 0.25-0.60; p-interaction<0.001). Conclusion: The MTRR rs1801394 and MTR rs1805087 genetic polymorphisms may modify the association between vitamin B2 and CRC risk, particularly in men. However, further studies are warranted to confirm these interaction.

Sex-specific associations of empirically derived dietary patterns with colorectal cancer risk in a Korean population: a case‒control study.

Dietary patterns may be a crucial modifiable factor in colorectal cancer (CRC) risk. This study aimed to examine the associations of dietary patterns derived from two methods with CRC risk in Korea. In a study of 1420 CRC patients and 2840 control participants, we obtained dietary patterns by principal component analysis (PCA) and reduced rank regression (RRR) using 33 predefined food groups. The associations between dietary patterns and CRC risk were assessed using unconditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). We identified two similar dietary patterns, derived from PCA 1 (prudent) and RRR (healthy), characterized by higher consumption of green/yellow vegetables, light-colored vegetables, fruits, eggs, and milk in both men and women. In women, higher prudent and healthy pattern scores were significantly associated with a lower risk of CRC (prudent, ORQ4 vs. Q1 = 0.59, 95% CI 0.40-0.86, P for trend = 0.005; healthy, ORQ4 vs. Q1 = 0.62, 95% CI 0.43-0.89, P for trend = 0.007). In men, a significant inverse association between dietary pattern and risk of rectal cancer was found only for the healthy dietary pattern (ORQ4 vs. Q1 = 0.66, 95% CI 0.45-0.97, P for trend = 0.036). Compared with the dietary pattern derived by PCA, the RRR dietary pattern had a slightly stronger association with a lower risk of distal colon cancer (ORQ4 vs. Q1 = 0.58, 95% CI 0.35-0.97, P for trend = 0.025) and rectal cancer (ORQ4 vs. Q1 = 0.29, 95% CI 0.15-0.57, P for trend < 0.001) in women. Our findings suggest cancer prevention strategies focusing on a diet rich in vegetables, fruits, eggs, and milk. Moreover, the use of both PCA and RRR methods may be advantageous to explore the associations between dietary patterns and risk of CRC.

The interaction effect of dietary selenium intake and the IL10 rs1800871 polymorphism on the risk of colorectal cancer: a case-control study in Korea.

The importance of Se in human health has received much attention due to its antioxidant properties when it is consumed at an appropriate level. However, the existing evidence is limited to obtain an effective conclusion for colorectal cancer (CRC). Notably, an adequate intake of Se was reported for Koreans. Furthermore, cytokine secretion and immune function may be affected by dietary Se. Our study aimed to explore whether Se potentially reduces CRC risk and whether the IL10 rs1800871 polymorphism has an effect on this association. We designed a case-control study with 1420 cases and 2840 controls. A semi-quantitative FFQ was used to obtain information on Se intake. We determined IL10 rs1800871 through genetic analysis. Different models were developed to explore Se intake related to CRC risk by calculating OR and 95 % CI using unconditional logistic regression. A reduced risk of CRC was found as Se intake increased, with an OR (95 % CI) of 0·44 (0·35, 0·55) (Pfor trend < 0·001). However, this association seems to be allele-specific and only present among risk variant allele carriers (GA/GG) with a significant interaction between dietary Se and IL10 rs1800871 (Pfor interaction = 0·043). We emphasised that a reduction in CRC risk is associated with appropriate Se intake. However, the IL10 rs1800871 polymorphism has an impact on this reduction, with a greater effect on variant allele carriers. These findings suggest the importance of considering an individual's genetic characteristics when developing nutritional strategies for CRC prevention.

The interaction between magnesium intake, the genetic variant INSR rs1799817 and colorectal cancer risk in a Korean population: a case-control study.

Magnesium may have a significant impact on the development of cancer. However, the relationship between magnesium intake and the risk of colorectal cancer (CRC) is unclear. Therefore, we evaluated the association between magnesium intake and the risk of CRC, and we investigated how the insulin receptor (INSR) rs1799817 variant impacts this relationship. Data from 1,420 CRC patients and 2,840 controls from the Korean National Cancer Centre were analysed. A higher intake of magnesium was associated with a reduced risk of CRC in the total population (odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.52-0.81). We found that G + carriers of INSR rs1799817 with higher magnesium intake had a significantly lower risk of CRC (p for interaction = 0.003). Our findings indicated that high magnesium intake could be associated with a decreased risk of CRC, and this association could be modified by the INSR rs1799817 variant.

Differential patterns of reproductive and lifestyle risk factors for breast cancer according to birth cohorts among women in China, Japan and Korea.

BACKGROUND: The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. METHODS: This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. RESULTS: Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66-1.13] compared to 0.60 [0.49-0.73], 0.46 [0.38-0.56] and 0.62 [0.51-0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14-1.84] compared to 1.25 [0.99-1.58], 1.06 [0.85-1.32] and 0.86 [0.69-1.08]) and alcohol consumption (1.22 [1.01-1.48] compared to 1.10 [0.90-1.33], 1.15 [0.96-1.38], and 1.07 [0.91-1.26]). CONCLUSION: We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium.

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2 ); normal (18.5-22.9 kg/m2 ); overweight (23-24.9 kg/m2 ); and obese (25+ kg/m2 ). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.

Lung Cancer Risk Prediction Models for Asian Ever-Smokers.

INTRODUCTION: Although lung cancer prediction models are widely used to support risk-based screening, their performance outside Western populations remains uncertain. This study aims to evaluate the performance of 11 existing risk prediction models in multiple Asian populations and to refit prediction models for Asians. METHODS: In a pooled analysis of 186,458 Asian ever-smokers from 19 prospective cohorts, we assessed calibration (expected-to-observed ratio) and discrimination (area under the receiver operating characteristic curve [AUC]) for each model. In addition, we developed the "Shanghai models" to better refine risk models for Asians on the basis of two well-characterized population-based prospective cohorts and externally validated them in other Asian cohorts. RESULTS: Among the 11 models, the Lung Cancer Death Risk Assessment Tool yielded the highest AUC (AUC [95% confidence interval (CI)] = 0.71 [0.67-0.74] for lung cancer death and 0.69 [0.67-0.72] for lung cancer incidence) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model had good calibration overall (expected-to-observed ratio [95% CI] = 1.06 [0.90-1.25]). Nevertheless, these models substantially underestimated lung cancer risk among Asians who reported less than 10 smoking pack-years or stopped smoking more than or equal to 20 years ago. The Shanghai models were found to have marginal improvement overall in discrimination (AUC [95% CI] = 0.72 [0.69-0.74] for lung cancer death and 0.70 [0.67-0.72] for lung cancer incidence) but consistently outperformed the selected Western models among low-intensity smokers and long-term quitters. CONCLUSIONS: The Shanghai models had comparable performance overall to the best existing models, but they improved much in predicting the lung cancer risk of low-intensity smokers and long-term quitters in Asia.

Functional Annotation and Gene Set Analysis of Gastric Cancer Risk Loci in a Korean Population.

PURPOSE: We aimed to identify the associated single nucleotide polymorphisms (SNPs) with gastric cancer (GC) risk by genome-wide association study (GWAS) and to explore the pathway enrichment of implicated genes and gene-sets with expression patterns. MATERIALS AND METHODS: The study population was comprised of 1,253 GC cases and 4,827 controls from National Cancer Center and an urban community of the Korean Genome Epidemiology Study and their genotyping was performed. SNPs were annotated, and mapped to genes to prioritize by three mapping approaches by functional mapping and annotation (FUMA). The gene-based analysis and gene-set analysis were conducted with full GWAS summary data using MAGMA. Gene-set pathway enrichment test with those prioritized genes were performed. RESULTS: In GWAS, rs2303771, a nonsynonymous variant of KLHDC4 gene was top SNP associated significantly with GC (odds ratio, 2.59; p=1.32×10-83). In post-GWAS, 71 genes were prioritized. In gene-based GWAS, seven genes were under significant p < 3.80×10-6 (0.05/13,114); DEFB108B had the lowest p=5.94×10-15, followed by FAM86C1 (p=1.74×10-14), PSCA (p=1.81×10-14), and KLHDC4 (p=5.00×10-10). In gene prioritizing, KLDHC4 was the only gene mapped with all three gene-mapping approaches. In pathway enrichment test with prioritized genes, FOLR2, PSCA, LY6K, LYPD2, and LY6E showed strong enrichment related to cellular component of membrane; a post-translation modification by synthesis of glycosylphosphatidylinositol (GPI)-anchored proteins pathway. CONCLUSION: While 37 SNPs were significantly associated with the risk of GC, genes involved in signaling pathways related to purine metabolism and GPI-anchored protein in cell membrane are pinpointed to be playing important role in GC.

Consumption of Sugar-Sweetened Soft Drinks and Risk of Gastrointestinal Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

INTRODUCTION: Previous observational studies have reported inconsistent findings on the association between consumption of sugar-sweetened soft drinks (SSSDs) and the risk of gastrointestinal (GI) cancer. This study investigated the associations between SSSD consumption and the risk of GI cancer using a systematic review and meta-analysis. METHODS: Observational epidemiological studies were searched from the PubMed and EMBASE databases until June 2021. We conducted a meta-analysis of all included studies and subgroup meta-analyses based on various factors. RESULTS: In a meta-analysis of 27 studies with nine case-control studies and 18 cohort studies, the consumption of SSSDs was modestly associated with an increased risk of GI cancer (odds ratio [OR]/relative risk [RR]: 1.08; 95% confidence interval [CI]: 1.01-1.16), with a significant positive dose-response relationship. In the subgroup meta-analysis by study design, there was a significant positive association between the consumption of SSSDs and GI cancer in cohort studies (RR: 1.11; 95% CI: 1.03-1.20; n = 18), but not in case-control studies. In the subgroup meta-analysis by type of cancer, consumption of SSSDs was significantly associated with an increased risk of colorectal cancer (OR/RR: 1.13; 95% CI: 1.07-1.19). CONCLUSIONS: This meta-analysis suggests that SSSD consumption significantly increases the risk of GI cancer, specifically colorectal cancer.

The association of diet-dependent acid load with colorectal cancer risk: a case-control study in Korea.

Acid-base disequilibrium is a contributor to cancer development because it affects molecular activities such as insulin-like growth factor 1 levels and adiponectin production. However, evidence of an association of diet-induced acid-base imbalance with colorectal cancer (CRC) is limited. We examined whether colorectal carcinogenesis is attributable to a diet with a high acid load. We recruited a total of 923 CRC cases and 1846 controls at the National Cancer Center in Korea for inclusion in a case-control study. We collected information on nutrient intake and specific clinical parameters of CRC by using a semiquantitative FFQ and medical records, respectively. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) were used to estimate diet-dependent acid load. We used an unconditional logistic regression model to analyse the association. Dietary acid load scores had a positive association with the odds of CRC (OR = 2·31 (95 % CI 1·79, 2·99) and OR = 2·14 (95 % CI 1·66, 2·76) for PRAL and NEAP, respectively, Pfor trend < 0·001). A stronger positive association was observed for females (OR = 3·09, 95 % CI 1·93, 4·94) than for males (OR = 1·71, 95 % CI 1·27, 2·31). Furthermore, acidogenic diets appeared to affect rectal cancer more strongly than colon cancer in females. Our study contributes to reinforcing epidemiological evidence regarding a detrimental effect of acidogenic diets on colorectal carcinogenesis. Thus, it is important to pay attention to the balance of acidogenic (e.g. poultry and red meat) and alkalinogenic foods (e.g. fruits and vegetables) in CRC prevention, especially for females.

A large-scale microRNA transcriptome-wide association study identifies two susceptibility microRNAs, miR-1307-5p and miR-192-3p, for colorectal cancer risk.

Transcriptome-wide association studies (TWAS) have identified many putative susceptibility genes for colorectal cancer (CRC) risk. However, susceptibility miRNAs, critical dysregulators of gene expression, remain unexplored. We genotyped DNA samples from 313 CRC East Asian patients and performed small RNA sequencing in their normal colon tissues distant from tumors to build genetic models for predicting miRNA expression. We applied these models and data from genome-wide association studies (GWAS) including 23 942 cases and 217 267 controls of East Asian ancestry to investigate associations of predicted miRNA expression with CRC risk. Perturbation experiments separately by promoting and inhibiting miRNAs expressions and further in vitro assays in both SW480 and HCT116 cells were conducted. At a Bonferroni-corrected threshold of P < 4.5 × 10-4, we identified two putative susceptibility miRNAs, miR-1307-5p and miR-192-3p, located in regions more than 500 kb away from any GWAS-identified risk variants in CRC. We observed that a high predicted expression of miR-1307-5p was associated with increased CRC risk, while a low predicted expression of miR-192-3p was associated with increased CRC risk. Our experimental results further provide strong evidence of their susceptible roles by showing that miR-1307-5p and miR-192-3p play a regulatory role, respectively, in promoting and inhibiting CRC cell proliferation, migration, and invasion, which was consistently observed in both SW480 and HCT116 cells. Our study provides additional insights into the biological mechanisms underlying CRC development.

Overproduction of Xanthophyll Pigment in Flavobacterium sp. JSWR-1 under Optimized Culture Conditions.

Flavobacterium can synthesize xanthophyll, particularly the pigment zeaxanthin, which has significant economic value in nutrition and pharmaceuticals. Recently, the use of carotenoid biosynthesis by bacteria and yeast fermentation technology has shown to be very efficient and offers significant advantages in large-scale production, cost-effectiveness, and safety. In the present study, JSWR-1 strain capable of producing xanthophyll pigment was isolated from a freshwater reservoir in Wanju-gun, Republic of Korea. Based on the morphological, physiological, and molecular characteristics, JSWR-1 classified as belonging to the Flavobacterium species. The bacterium is strictly aerobic, Gram-negative, rod-shaped, and psychrophilic. The completed genome sequence of the strain Flavobacterium sp. JSWR-1 is predicted to be a single circular 3,425,829-bp chromosome with a G+C content of 35.2% and 2,941 protein-coding genes. The optimization of carotenoid production was achieved by small-scale cultivation, resulting in zeaxanthin being identified as the predominant carotenoid pigment. The enhancement of zeaxanthin biosynthesis by applying different light-irradiation, variations in pH and temperature, and adding carbon and nitrogen supplies to the growth medium. A significant increase in intracellular zeaxanthin concentrations was also recorded during fed-batch fermentation achieving a maximum of 16.69 ± 0.71 mg/l, corresponding to a product yield of 4.05 ± 0.15 mg zeaxanthin per gram cell dry weight. Batch and fed-batch culture extracts exhibit significant antioxidant activity. The results demonstrated that the JSWR-1 strain can potentially serve as a source for zeaxanthin biosynthesis.

Dietary intake and cancer incidence in Korean adults: a systematic review and meta-analysis of observational studies.

Cancer is a major health burden in Korea, and dietary factors have been suggested as putative risk factors for cancer development at various sites. This study systematically reviewed the published literature investigating the associations between dietary factors and cancer incidence among Korean adults, following the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines. We focused on the 5 most studied cancer sites (stomach, colorectum, breast, thyroid, and cervix) as outcomes and dietary exposures with evidence levels greater than limited-suggestive according to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) panel's judgment for any of the cancer sites. This resulted in the inclusion of 72 studies. Pooled estimates of the impact of dietary factors on cancer risk suggested protective associations of fruits and vegetables with risks for gastric cancer (GC), colorectal cancer (CRC), and breast cancer (BC) and dietary vitamin C with the risk of GC, as well as a harmful association between fermented soy products and the risk of GC. Despite the limited number of studies, we observed consistent protective associations of dietary fiber with GC and dietary fiber, coffee, and calcium with CRC. These findings are largely consistent with the WCRF/AICR expert report. However, pooled estimates for the associations of other salt-preserved foods with GC, meat with CRC, and dietary carotenoids and dairy products with BC did not reach statistical significance. Further studies with prospective designs, larger sample sizes, and diverse types of dietary factors and cancer sites are necessary.