Analysis of Meis2 knockout mice reveals Sonic hedgehog-mediated patterning of the cochlear duct.

BACKGROUND: The mechanisms underlying the formation of complex structures such as during the outgrowth of the cochlear duct are still poorly understood. RESULTS: We have analyzed the morphological and molecular changes associated with cochlear development in mouse mutants for the transcription factor Meis2, which show defective coiling of the cochlea. These morphological abnormalities were accompanied by the formation of ectopic and extra rows of sensory hair cells. Gene profiling of otic vesicles from Meis2 mutants revealed a dysregulation of genes that are potentially involved in Sonic hedgehog (Shh)-mediated patterning of the cochlear duct. Like in Shh mutants, Meis2 defective mice showed a loss of genes that are expressed in the apical part of the cochlear duct. CONCLUSIONS: Taken together, these data reveal that the loss of Meis2 leads to a phenotype that resembles Shh mutants, suggesting that Meis2 is instrumental for cochlear Shh signaling. The modulation of the same subset of genes provides an interesting insight into which Shh responsive genes are essential for outgrowth and patterning of the cochlear duct.

A higher dietary alpha-linolenic acid intake is associated with lower colorectal cancer risk based on MUC4 rs2246901 variant among Korean adults.

Alpha-linolenic acid (C18:3n-3 [ALA]) intake may have a beneficial effect in reducing cancer risk; however, its association with colorectal cancer (CRC) risk remains conflicted. Additionally, ALA was emphasized as being associated with mucins, an important glycoproteins family within the intestine. Thus, we hypothesized that a higher dietary ALA intake may reduce the risk of CRC and this preventive effect has an interaction with mucin 4 (MUC4) rs2246901. We conducted a case-control study at the National Cancer Center in Korea, involving 1039 cases and 1982 controls, aiming to determine the interaction of the MUC4 rs2246901 polymorphism and ALA intake in CRC risk. Dietary ALA intake was collected via semiquantitative food frequency questionnaire (SQFFQ), categorizing by 4 quartiles. We evaluated the odds ratios (ORs) and 95% confidence intervals (CIs) through unconditional logistic regression models. Higher dietary ALA intake was found to be inversely associated with CRC risk (adjusted OR = 0.58; 95% CI, 0.45-0.75, P for trend < .001). No significant association between MUC4 rs2246901 polymorphism and CRC risk was found. In a recessive model, MUC4 rs2246901 seemed to modify this association; participants with at least 1 major allele and higher ALA intake had a significantly lower CRC risk than those who had a lower intake (adjusted OR = 0.56; 95% CI, 0.43-0.72; P interaction = .047). A higher dietary ALA was proposed as a potential protective nutrient against CRC. Moreover, this association might be influenced by presence of the MUC4 rs2246901 polymorphism.

Tumor Deposits as an Adverse Prognostic Indicator in Stage III Colon Cancer: A Multicenter Database Study.

Objective: We explored the oncological impact of tumor deposits (TDs) on colon cancer and proposed optimal modifications to the current staging system. Background: In the existing American Joint Committee on Cancer colon cancer staging system, TDs are incorporated into the N category as N1c. When lymph node metastases (LNMs) are present, their number is considered to determine nodal stages, such as N1a/b or N2a/b, regardless of TDs. Methods: 4212 patients with primary colon cancer who underwent surgical resection in the Seoul Colorectal Group (2010-2020) and 93,057 patients from the Surveillance, Epidemiology, and End Results*Stat database (2000-2017) were included in this study. Patients were classified according to the number of metastatic lymph nodes (LNs) (0/1-3/≥4) and the presence of TDs. Results: TDs were significantly associated with left colon cancer, a higher T category, and vascular/perineural invasion. Patients with TDs had higher recurrence rates (23.1 vs 7.5%, P < 0.001). The TD-positive patients had notably worse overall survival (OS) and recurrence-free survival rates. The survival outcomes of TD-positive patients without LNM were inferior to those of TD-negative patients with LN1-3 (5-year OS: 78.9 vs 87.8%, P = 0.04). The survival outcomes of TD-positive patients with LN1-3 were similar to those of TD-negative patients with LN ≥4 (5-year OS: 87.0 vs 77.1%, P = 0.11). Survival outcomes obtained using the Surveillance, Epidemiology, and End Results *Stat database yielded consistent results. Conclusions: TDs were associated with poor prognostic factors and had a significant impact on survival outcomes. The incorporation of tumor deposits into nodal classifications beyond the current N1c criteria may improve the staging system and more accurately reflect the recurrence and survival rates among patients with colon cancer. TD-positive in N1a or N1b could be categorized as N2.

Relationship Between Aspirin Use and Site-Specific Colorectal Cancer Risk Among Individuals With Metabolic Comorbidity.

BACKGROUND: The relationship between aspirin usage and the risk of colorectal cancer (CRC) among individuals with both hypertension (HTN) and diabetes mellitus (DM) remains unclear. This study aims to explore the impact of aspirin use on the site-specific CRC risk in patients with metabolic comorbidity. METHODS: A case-control study was conducted among 1,331 CRC patients and 2,771 controls recruited from the Nation Cancer Center in Korea. Multinomial logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between aspirin use, metabolic disease status, and site-specific CRC risk. RESULTS: Among the 4,102 participants, 1,191 individuals had neither HTN nor DM, 2,044 were diagnosed with HTN, 203 with DM, and 664 presented with HTN and DM comorbidity. An increasing number of HTN and DM was associated with an increased risk of overall CRC (HTN or DM: OR, 1.70; 95% CI, 1.39-2.07; HTN and DM: OR, 8.43; 95% CI, 6.37-11.16), while aspirin use was associated with a decreased risk of overall CRC (OR, 0.31; 95% CI, 0.21-0.46). These results remained consistent across anatomical sites. Among individuals with HTN and DM comorbidity, aspirin use notably associated with lower risk of overall CRC (OR, 0.39; 95% CI, 0.21-0.72), proximal colon (OR, 0.32; 95% CI, 0.13-0.71) and rectal cancer (OR, 0.27; 95% CI, 0.08-0.97), but not distal colon cancer (OR, 0.58; 95% CI, 0.27-1.24). CONCLUSION: This study showed that aspirin use is negatively associated with overall and site-specific CRC, even among individuals with HTN and DM comorbidity.

Fecal Microbial Dysbiosis is Associated with Colorectal Cancer Risk in a Korean Population.

Purpose: The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking. Materials and Methods: In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2. Results: There is a significant divergence of the microbial composition between CRC patients and controls (PERMANOVA p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (OR: 6.93, 95% CI: 3.98-12.06, p-trend<0.001) compared to those in the lowest tertile. Similar results were found for men (OR: 6.28, 95% CI: 3.04-12.98-, p-trend<0.001) and women (OR: 7.39, 95% CI: 3.10-17.63, p-trend<0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples. Conclusion: Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.

Are sporadic colorectal cancers in young patients distinct from those in elderly patients?

AIM: The aim of this study was to compare the clinicopathological and oncological characteristics of sporadic colorectal cancer (CRC) between young and elderly patients without any genetic mutations that cause hereditary CRC. METHOD: In this cross-sectional, retrospective study conducted at three tertiary referral hospitals, we enrolled 1599 patients with CRC who underwent surgery between January 2010 and December 2017, including 157 young patients (age ≤ 40 years; yCRC) and 1442 elderly patients (age ≥ 70 years; eCRC). The clinicopathological and oncological outcomes were compared between the two groups. RESULTS: The median age at diagnosis was 37 years in the yCRC group (range 33.0-39.2 years) and 76 years in the eCRC group (range 72.0-79.0 years). The yCRC group did not present with advanced stages at diagnosis compared with the eCRC group, and the distribution of tumour stages was similar between the two groups. Microsatellite instability (MSI) testing revealed no difference in the frequency of tumours with high MSI (7.8% in yCRC, 5.8% in eCRC), and the frequency of mutations in the KRAS, NRAS and BRAF genes was also similar. The 3-year overall survival was better in the yCRC group than in the eCRC group (97.4% vs. 83.5%, p < 0.001); however, no such difference was observed in cancer-specific survival. CONCLUSION: Genetically proven sporadic CRCs did not differ significantly between young and elderly patients in terms of tumour stage, tumour location and various molecular features. CLINICAL TRIAL REGISTRATION NUMBER: The study was retrospectively registered with Clinical Trials.gov (no. NCT05601609).

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 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.

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.

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 to 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 to 1.83). Males 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 to 0.54; p-interaction=0.02). In MTR rs1805087, males 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 to 0.60; p-interaction<0.001). CONCLUSIONS: The MTRR rs1801394 and MTR rs1805087 genetic polymorphisms may modify the association between vitamin B2 and CRC risk, particularly in males. However, further studies are warranted to confirm these interaction results.

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 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.

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.

Long-term clinical outcomes after high and low ligations with lymph node dissection around the root of the inferior mesenteric artery in patients with rectal cancer.

PURPOSE: This study aimed to evaluate the long-term clinical outcomes based on the ligation level of the inferior mesenteric artery (IMA) in patients with rectal cancer. METHODS: This was a retrospective analysis of a prospectively collected database that included all patients who underwent elective low anterior resection for rectal cancer between January 2013 and December 2019. The clinical outcomes included oncological outcomes, postoperative complications, and functional outcomes. The oncological outcomes included overall survival (OS) and relapse-free survival (RFS). The functional outcomes, including defecatory and urogenital functions, were analyzed using the Fecal Incontinence Severity Index, International Prostate Symptom Score, and International Index of Erectile Function questionnaires. RESULTS: In total, 545 patients were included in the analysis. Of these, 244 patients underwent high ligation (HL), whereas 301 underwent low ligation (LL). The tumor size was larger in the HL group than in the LL group. The number of harvested lymph nodes (LNs) was higher in the HL group than in the LL group. There were no significant differences in complication rates and recurrence patterns between the groups. There were no significant differences in 5-year RFS and OS between the groups. Cox regression analysis revealed that the ligation level (HL vs. LL) was not a significant risk factor for oncological outcomes. Regarding functional outcomes, the LL group showed a significant recovery in defecatory function 1 year postoperatively compared with the HL group. CONCLUSION: LL with LNs dissection around the root of the IMA might not affect the oncologic outcomes comparing to HL; however, it has minimal benefit for defecatory function.

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.

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.

Exfoliate cancer cell analysis in rectal cancer surgery: comparison of laparoscopic and transanal total mesorectal excision, a pilot study.

PURPOSE: Minimally invasive surgery (MIS) is currently the standard treatment for rectal cancer. However, its limitations include complications and incomplete total mesorectal resection (TME) due to anatomical features and technical difficulties. Transanal TME (TaTME) has been practiced since 2010 to improve this, but there is a risk of local recurrence and intra-abdominal contamination. We aimed to analyze samples obtained through lavage to compare laparoscopic TME (LapTME) and TaTME. METHODS: From June 2020 to January 2021, 20 patients with rectal cancer undergoing MIS were consecutively and prospectively recruited. Samples were collected at the start of surgery, immediately after TME, and after irrigation. The samples were analyzed for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) through a quantitative real-time polymerase chain reaction. The primary outcome was to compare the detected amounts of CEA and CK20 immediately after TME between the surgical methods. RESULTS: Among the 20 patients, 13 underwent LapTME and 7 underwent TaTME. Tumor location was lower in TaTME (7.3 cm vs. 4.6 cm, P=0.012), and negative mesorectal fascia (MRF) was more in LapTME (76.9% vs. 28.6%, P=0.044). CEA and CK20 levels were high in 3 patients (42.9%) only in TaTME. There was 1 case of T4 with incomplete purse-string suture and 1 case of positive MRF with dissection failure. All patients were followed up for an average of 32.5 months without local recurrence. CONCLUSION: CEA and CK20 levels were high only in TaTME and were related to tumor factors or intraoperative events. However, whether the detection amount is clinically related to local recurrence remains unclear.

Interaction between vitamin E intake and a COMT gene variant on colorectal cancer risk among Korean adults: a case-control study.

OBJECTIVES: Previous human trials have not supported the anticarcinogenic effect of vitamin E despite biological plausibility and considerable epidemiological evidence. A possible explanation for this inconsistency is the interactive effect of the catechol-O-methyltransferase (COMT) gene and supplemental vitamin E on cancer. We examined whether a COMT gene variant modulates the effect of dietary vitamin E intake on colorectal cancer (CRC) risk. METHODS: In this case-control study of Korean adults (975 cases and 975 age- and sex-matched controls), dietary vitamin E density (mg/1,000 kcal) was measured using a semiquantitative food frequency questionnaire, COMT single nucleotide polymorphism (SNP) rs740603 (A>G) was genotyped, and CRC was verified histologically. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models with adjustments for potential confounders. RESULTS: Higher vitamin E density was associated with a lower risk of CRC (highest vs. lowest quartiles: OR, 0.72; 95% CI, 0.55 to 0.96; p-for-trend=0.002). When stratified by COMT SNP rs740603 genotype, the inverse association between vitamin E density and CRC risk was confined to those with at least 1 A allele (≥median vs.

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations.

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.

Zinc intake, SLC30A8 rs3802177 polymorphism, and colorectal cancer risk in a Korean population: a case-control study.

PURPOSE: Zinc is an essential micronutrient involving in multiple enzymatic reactions of human metabolism and biological functions affecting the cancer development. However, the relationship between dietary zinc intake and colorectal cancer (CRC) risk has been unclear. Herein, our study investigated the relationship between dietary zinc intake and CRC risk, and examined how the SLC30A8 rs3802177 genetic variant affects this association. METHODS: A total of 1431 CRC cases and 2704 controls were selected to investigate the relationship between dietary zinc intake and CRC risk. After excluding individuals without genotype data, 1097 CRC cases and 1559 controls were used to evaluate the interaction between dietary zinc intake and the rs3802177 polymorphism in CRC risk. The odds ratios (ORs) and 95% confidence intervals (CIs) were measured using unconditional logistic regression models. RESULTS: Higher dietary zinc intake was inversely associated with the risk of CRC in the total population [adjusted OR (aOR) = 0.80, 95% CI 0.66-0.96, p for trend = 0.018]. In the codominant model, G+ carriers of the SLC30A8 rs3802177 with higher consumption of zinc were observed to have a significantly lower risk of CRC in all participants (p for interaction = 0.020). In females, GG carriers with higher zinc intake showed a stronger protective effect against the development of CRC (p for interaction = 0.008). CONCLUSIONS: In summary, our findings suggest an inverse association between dietary zinc intake and CRC risk, and this relationship may be modified by SLC30A8 rs3802177 polymorphism.