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1.
Pathology ; 56(4): 528-539, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38609782

RESUMO

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.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Microambiente Tumoral , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/cirurgia , Microambiente Tumoral/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fezes/microbiologia , Adulto , Idoso de 80 Anos ou mais , RNA Ribossômico 16S/genética , Prognóstico , Bacteroides fragilis/imunologia
2.
Nat Commun ; 15(1): 3557, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38670944

RESUMO

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.


Assuntos
Povo Asiático , Neoplasias Colorretais , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , População Branca , Humanos , Neoplasias Colorretais/genética , Povo Asiático/genética , População Branca/genética , Sequenciamento do Exoma , Estudos de Casos e Controles , Transcriptoma , Mapeamento Cromossômico , Masculino , Feminino , População do Leste Asiático
3.
Br J Nutr ; : 1-10, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38508770

RESUMO

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.

4.
Sci Rep ; 14(1): 6709, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509114

RESUMO

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.


Assuntos
Neoplasias Colorretais , Neoplasias Retais , Masculino , Humanos , Feminino , Fatores de Risco , Estudos de Casos e Controles , Padrões Dietéticos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Dieta , Verduras , República da Coreia/epidemiologia
5.
Epidemiol Health ; : e2024037, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38514198

RESUMO

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.

6.
Curr Dev Nutr ; 8(3): 102127, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38523829

RESUMO

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.

7.
Ann Coloproctol ; 40(1): 62-73, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38414122

RESUMO

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.

8.
Int J Food Sci Nutr ; : 1-11, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389245

RESUMO

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.

9.
Br J Nutr ; 131(2): 333-342, 2024 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-37649268

RESUMO

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.


Assuntos
Neoplasias Colorretais , Dieta , Masculino , Feminino , Humanos , Fatores de Risco , Estudos de Casos e Controles , Dieta/efeitos adversos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Carcinogênese , República da Coreia/epidemiologia
10.
Hum Mol Genet ; 33(4): 333-341, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37903058

RESUMO

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.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transcriptoma/genética , Estudo de Associação Genômica Ampla , Neoplasias Colorretais/metabolismo , Células HCT116 , Regulação Neoplásica da Expressão Gênica/genética , Proliferação de Células/genética
11.
Ann Coloproctol ; 39(6): 502-512, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38145898

RESUMO

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.

12.
Epidemiol Health ; 45: e2023100, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37974041

RESUMO

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.

Assuntos
Catecol O-Metiltransferase , Neoplasias Colorretais , Adulto , Humanos , Catecol O-Metiltransferase/genética , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Vitamina E , Modelos Logísticos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , República da Coreia/epidemiologia , Fatores de Risco
13.
Nat Commun ; 14(1): 6147, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37783704

RESUMO

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.


Assuntos
Neoplasias Colorretais , Etnicidade , Humanos , Etnicidade/genética , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Herança Multifatorial , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética
14.
J Cancer Res Clin Oncol ; 149(18): 16429-16440, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37707576

RESUMO

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.


Assuntos
Neoplasias Colorretais , Feminino , Humanos , Estudos de Casos e Controles , Modelos Logísticos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Zinco , República da Coreia/epidemiologia , Fatores de Risco , Transportador 8 de Zinco
15.
BMC Cancer ; 23(1): 734, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37553666

RESUMO

BACKGROUND: For locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) may enhance tumour response, reduce recurrence, and improve patient compliance compared to upfront surgery. Recent studies have shown that chemoradiotherapy (CRT) followed by consolidation chemotherapy leads to higher rate of pathologic complete response (pCR) than induction chemotherapy followed by CRT. However, an optimal TNT regimen that maximise the pCR rate and minimise toxicity has not been established. Therefore, the aim of this trial was to investigate whether preoperative short-course radiotherapy followed by chemotherapy with four cycles of CAPOX can double the pCR rate compared to a standard schedule of long-course preoperative CRT in patients with LARC. METHODS: This is a multi-centre, prospective, open label, randomised controlled trial. Patients with clinical primary tumour stage 3 and higher or regional node-involved rectal cancer located within 10 cm from the anal verge were randomly assigned equally to short-course radiotherapy (25 Gy in 5 fractions over 1 week) followed by four cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) (TNT) or CRT (50.4 Gy in 28 fractions over 5 weeks, concurrently with concomitant oral capecitabine 825 mg/m2 twice a day). After preoperative treatment, total mesorectal excision was performed 2-4 weeks in the TNT group and 6-10 weeks in the CRT group, followed by optional additional adjuvant chemotherapy. The primary endpoint is the pCR rate, and secondary endpoints include disease-related treatment failure, quality of life, and cost-effectiveness. Assuming a pCR rate of 28% and 15% in the TNT and CRT groups, respectively, and one-side alpha error rate of 0.025 and power of 80%, 348 patients will be enrolled considering 10% dropout rate. DISCUSSION: The TV-LARK trial will evaluate the superiority of employed TNT regimen against the standard CRT regimen for patients with LARC. We aimed to identify a TNT regimen that will improve the pCR rate and decrease systemic recurrence in these patients. TRIAL REGISTRATION: Cris.nih.go.kr ID: KCT0007169 (April 08, 2022). The posted information will be updated as needed to reflect the protocol amendments and study progress.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Terapia Neoadjuvante/métodos , Capecitabina/uso terapêutico , Resultado do Tratamento , Estudos Prospectivos , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Quimiorradioterapia/métodos , República da Coreia/epidemiologia , Fluoruracila , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
16.
Int J Colorectal Dis ; 38(1): 167, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37300565

RESUMO

PURPOSE: Endoscopic resection (ER) is a reliable treatment for early colorectal cancer without lymph node metastasis. We aimed to examine the effects of ER performed prior to T1 colorectal cancer (T1 CRC) surgery by comparing long-term survival after radical surgery with prior ER to that after radical surgery alone. METHODS: This retrospective study included patients who underwent surgical resection of T1 CRC at the National Cancer Center, Korea, between 2003 and 2017. All eligible patients (n = 543) were divided into primary and secondary surgery groups. To ensure similar characteristics between the groups, 1:1 propensity score matching was used. Baseline characteristics, gross and histological features, along with postoperative recurrence-free survival (RFS) between the two groups were compared. Cox proportional hazard model was used to identify the risk factors affecting recurrence after surgery. Cost analysis was performed to examine the cost-effectiveness of ER and radical surgeries. RESULTS: No significant differences were observed in 5-year RFS between the two groups in matched data (96.9% vs. 95.5%, p = 0.596) and in the unadjusted model (97.2% vs. 96.8%, p = 0.930). This difference was also similar in subgroup analyses based on node status and high-risk histologic features. ER before surgery did not increase the medical costs of radical surgery. CONCLUSION: ER prior to radical surgery did not affect the long-term oncologic outcomes of T1 CRC or significantly increased the medical costs. Attempting ER first for suspected T1 CRC would be a good strategy to avoid unnecessary surgery without concerns of worsening cancer-related prognosis.


Assuntos
Neoplasias Colorretais , Humanos , Estudos Retrospectivos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Metástase Linfática , Resultado do Tratamento
17.
Int J Food Sci Nutr ; 74(4): 510-521, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37282563

RESUMO

Vitamin E and paraoxonase 1 (PON1) are associated with cancer development. However, their interactive effect on colorectal cancer (CRC) risk is inconclusive. We conducted a case-control study including 1,351 CRC patients and 2,670 controls at the Korean National Cancer Centre (KNCC). There was an inverse association between vitamin E intake and CRC risk (odds ratio (OR) = 0.31; 95% confidence interval (CI) = 0.22-0.42). We identified a reduced CRC risk among individuals with CC genotype of PON1 rs662 polymorphism compared with subjects carrying the T allele (OR = 0.74; 95% CI = 0.61-0.90). The highest interaction between vitamin E intake and PON1 rs662 variants was significant for the subjects carrying the CC genotype (p-interaction = 0.014). This study provided further supporting evidence that vitamin E intake is associated with lower odds of CRC. Furthermore, the activity of vitamin E is strengthened among individuals carrying C allele of the PON1 rs662 polymorphism.


Assuntos
Arildialquilfosfatase , Neoplasias Colorretais , Humanos , Arildialquilfosfatase/genética , Estudos de Casos e Controles , Polimorfismo Genético , Genótipo , Vitamina E , Neoplasias Colorretais/genética , República da Coreia/epidemiologia , Polimorfismo de Nucleotídeo Único
18.
Sci Rep ; 13(1): 10187, 2023 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349365

RESUMO

This study aimed to examine whether the ISX rs5755368 genotypes are associated with the effect of dietary retinol consumption on CRC risk. We recruited 923 CRC patients and 1846 controls to identify the association between dietary retinol and CRC risk. Dietary retinol intake was assessed using a semiquantitative food frequency questionnaire. Genotype data were available for 1419 patients (600 cases and 819 controls) of the total study population. Genotyping was performed using an Illumina MEGA Expanded Array. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression models. Retinol intake was inversely associated with CRC (OR = 0.49; 95% CI = 0.37-0.63). Participants with AA genotype showed lower CRC risk than subjects carrying the G allele (AG + GG) (OR = 0.76; 95% CI = 0.58-0.99). A 68% reduced risk of CRC was related to subjects who had the highest retinol intake and carrying AA genotype compared to the risk of participants consumed the lowest retinol intake and carrying the G allele (OR = 0.32; 95% CI = 0.20-0.53; P interaction = 0.026). Retinol intake could be a protective factor for CRC risk while this association could be strengthened among individuals carrying the homozygous AA genotype.


Assuntos
Neoplasias Colorretais , Vitamina A , Humanos , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Genótipo , Modelos Logísticos , Polimorfismo de Nucleotídeo Único , República da Coreia/epidemiologia , Fatores de Risco
19.
Int. arch. otorhinolaryngol. (Impr.) ; 27(2): 191-196, April-June 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1440217

RESUMO

Abstract Introduction Contact granulomas (CGs) and intubation granulomas (IGs) are known to have different clinical manifestations despite having the same pathological features. Objectives The purpose of the present study was to analyze the treatment results for CG and IG and to obtain clinical information. Methods We retrospectively reviewed the medical records of patients diagnosed with vocal process granuloma (VPG) between January 2015 and December 2018. The patient's age, sex, medical history, lesion size, lesion type, reflux finding score (RFS), response to treatment, duration of treatment, and follow-up period were compared. Results Eighteen patients with CG and 14 patients with IG were included in the study. The IG group had more female patients (p = 0.0009), showed better response to proton pump inhibitor (PPI) and steroid inhalation (SI) (p = 0.036), and had a shorter treatment period (p = 0.0029) than the CG group. Five patients who received botulinum toxin injections in their vocal cords had complete remission. Conclusions Compared with CG, IG was more responsive to treatment with PPI and SI and required a shorter duration of treatment.

20.
Int Arch Otorhinolaryngol ; 27(2): e191-e196, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37125377

RESUMO

Introduction Contact granulomas (CGs) and intubation granulomas (IGs) are known to have different clinical manifestations despite having the same pathological features. Objective The purpose of the present study was to analyze the treatment results for CG and IG and to obtain clinical information. Methods We retrospectively reviewed the medical records of patients diagnosed with vocal process granuloma (VPG) between January 2015 and December 2018. The patient's age, sex, medical history, lesion size, lesion type, reflux finding score (RFS), response to treatment, duration of treatment, and follow-up period were compared. Results Eighteen patients with CG and 14 patients with IG were included in the study. The IG group had more female patients ( p = 0.0009), showed better response to proton pump inhibitor (PPI) and steroid inhalation (SI) ( p = 0.036), and had a shorter treatment period ( p = 0.0029) than the CG group. Five patients who received botulinum toxin injections in their vocal cords had complete remission. Conclusion Compared with CG, IG was more responsive to treatment with PPI and SI and required a shorter duration of treatment.

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