RESUMO
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.
RESUMO
Breast cancer (BrCa) remains a significant health concern globally, influenced by both nonmodifiable and modifiable risk factors. Limited studies have explored the role of color-specific vegetables and fruits, which are rich in specific phytonutrients, on BrCa risk. We hypothesized that consuming color-specific vegetables and fruits may decrease BrCa risk in Korean women. This case-control study examined the relationship between the intake of different-colored vegetables and fruits and the risk of BrCa, considering menopausal, hormone receptor status, tumor subtypes. We matched 395 patients and 395 controls by age and recruited from the National Cancer Center in Korea. Dietary data was collected via food frequency questionnaire, categorizing by colors: green, orange/yellow, red/purple, and white. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by logistic regression models, with subgroup analyses for menopausal, hormone receptor status, and tumor subtypes. Results shown BrCa patients consumed less vegetables and fruits than control group. Higher consumption of green, other orange/yellow, and white vegetables and fruits was negatively associated with BrCa risk [OR (95% CIs) of Q4 vs Q1 = 0.59 (0.36-0.94); 0.55 (0.33-0.89); and 0.60 (0.37-0.96), respectively]. Particularly, a greater intake of dark green leafy vegetables was significantly associated with reduced BrCa risk (OR of Q4 vs Q1 = 0.55, 95% CI = 0.34-0.89). Subgroup analysis consistently demonstrated inverse associations between higher intake of green-color vegetables and fruits and BrCa risk. Our findings suggest that a diet rich in green and white-color vegetables and fruits may lower BrCa risk among Korean women.
Assuntos
Neoplasias da Mama , Dieta , Frutas , Verduras , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Inquéritos sobre Dietas , Razão de Chances , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
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.
Assuntos
Aspirina , Neoplasias Colorretais , Comorbidade , Hipertensão , Humanos , Aspirina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Idoso , Razão de Chances , Hipertensão/epidemiologia , Hipertensão/complicações , Fatores de Risco , Modelos Logísticos , Diabetes Mellitus/epidemiologia , República da Coreia/epidemiologia , AdultoRESUMO
The association between dietary carotenoids and breast cancer (BC) risks were inconsistent. Therefore, this study investigated the association between dietary carotenoid and BC risks among Korean women. We recruited participants from the National Cancer Centre of Korea. Odds ratios and 95% confidence intervals were calculated with a logistic regression model. There was an inverse association between dietary carotenoid subclasses and BC risks; in particular, a higher intake of ß-carotene and lutein/zeaxanthin was associated with reduced BC risks. After subgroup analysis with estrogen receptor (ER)/progesterone receptor (PR) status, there was similar trend among ER-/PR- women. We further investigated which foods contribute to the carotenoid intake. A higher intake of radish leaves, kale, and bracken was associated with lowered BC risks. Accordingly, dietary carotenoid, particularly ß-carotene and lutein/zeaxanthin, appears to be associated with a lower risk of BC among Korean women.
Assuntos
Neoplasias da Mama , Carotenoides , Dieta , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , República da Coreia/epidemiologia , Carotenoides/administração & dosagem , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto , Fatores de Risco , beta Caroteno/administração & dosagem , Luteína/administração & dosagem , Zeaxantinas/administração & dosagem , Receptores de Progesterona/metabolismo , Receptores de Estrogênio/metabolismo , Razão de Chances , IdosoRESUMO
OBJECTIVES: Mercury can stimulate immune responses through T helper 17 (Th17). The gene IL23R is a key factor in Th17 function, which may also contribute to digestive tract diseases. The aim of this study was to identify the associations between dietary mercury and gastric cancer (GC) and to investigate whether the IL23R rs10889677 polymorphism modifies those associations. METHODS: This case-control study included 377 patients with GC and 756 healthy controls. Dietary mercury intake (total mercury and methylmercury) was assessed using a dietary heavy metal database incorporated into the food frequency questionnaire. IL23R genetic polymorphism rs10889677 (A>C) was genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression models with adjustments for potential confounders. RESULTS: A higher dietary methylmercury intake was associated with an elevated risk of GC (OR for the highest vs. lowest tertile [T3 vs. T1], 2.02; 95% CI, 1.41 to 2.91; p for trend <0.001). The IL23R rs10889677 reduced the risk of GC in individuals who carried at least 1 minor allele (OR, 0.62; 95% CI, 0.46 to 0.83; p=0.001; AC/CC vs. AA). Individuals with a C allele exhibited a lower susceptibility to GC through methylmercury intake than those with the AA genotype (OR for the T3 of methylmercury and AA carriers, 2.93; 95% CI, 1.77 to 4.87; and OR for the T3 of methylmercury and AC/CC genotype, 1.30; 95% CI, 0.76 to 2.21; p-interaction=0.013). CONCLUSIONS: Our findings suggest that a genetic polymorphism, rs10889677 in IL23R, plays a role in modifying the association between dietary methylmercury intake and the risk of GC.
Assuntos
Mercúrio , Receptores de Interleucina , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/epidemiologia , Masculino , Feminino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Receptores de Interleucina/genética , República da Coreia/epidemiologia , Idoso , Dieta/estatística & dados numéricos , Polimorfismo de Nucleotídeo Único , Adulto , Fatores de Risco , Predisposição Genética para DoençaRESUMO
BACKGROUND: The exosome-mediated extracellular secretion of miRNAs occurs in many cancers, and RAB27A is a potent regulator of exosome secretion. For metastatic renal cell carcinoma (RCC), this study examines the mechanisms of cancer metastasis via the RAB27A-regulated secretion of specific miRNAs. METHODS: RAB27A knockdown (KD) and overexpressing (OE) RCC cells were used to examine cell migration and adhesion. The particle counts and sizes of exosomes in RAB27A OE cells were analyzed using Exoview, and those of intraluminal vesicles (ILV) and multivesicular bodies (MVB) were measured using an electron microscope. Analysis of RNA sequences, protein-protein interaction networks, and the competing endogenous RNA (ceRNA) network were used to identify representative downregulated miRNAs that are likely to undergo cargo-sorting into exosomes and subsequent secretion. A molecular beacon of miR-137-3p, one of the most representatively downregulated genes with a fold change of 339, was produced, and its secretion was analyzed using Exoview. RAB27A OE and control cells were incubated in an exosome-containing media to determine the uptake of tumor suppressor miRNAs that affect cancer cell metastasis. RESULTS: Migration and cell adhesion were higher in RAB27A OE cells than in RAB27A KD cells. Electron microscopy revealed that the numbers of multivesicular bodies and intraluminal vesicles per cell were higher in RAB27A OE cells than in control cells, suggesting their secretion. The finding revealed that miR-127-3p was sorted into exosomes and disposed of extracellularly. Protein-protein interaction analysis revealed MYCN to be the most significant hub for RAB27A-OE RCC cells. ceRNA network analysis revealed that MAPK4 interacted strongly with miR-127-3p. CONCLUSION: The disposal of miR-127-3p through exosome secretion in RAB27A overexpressing cells may not inhibit the MAPK pathway to gain metastatic potential by activating MYCN. The exosomes containing miRNAs are valuable therapeutic targets for cancer treatment.
RESUMO
BACKGROUND: During sentinel node navigation surgery in patients with gastric cancer, intraoperative pathologic examination of sentinel nodes is crucial in determining the extent of surgery. In this study, we evaluated the feasibility and accuracy of intraoperative pathologic protocols using data from a prospective, multicenter, randomized trial. METHODS: A retrospective analysis was conducted using data from the SEntinel Node ORIented Tailored Approach trials from 2013 to 2016. All sentinel lymph nodes were evaluated during surgery with hematoxylin-eosin (HE) staining using a representative section at the largest plane for lymph nodes. For permanent histologic evaluation, sentinel basin nodes were stained with HE and cytokeratin immunohistochemistry in formalin-fixed, paraffin-embedded (FFPE) sections and examined with HE for three deeper-step sections at 200-µm intervals. The failure rate of identification by frozen section and the metastasis rate in non-sentinel basins were investigated. RESULTS: Of the 237 patients who underwent sentinel node basin dissection, 30 had lymph node metastases on permanent pathology. Thirteen patients had macrometastasis confirmed in frozen sections as well as FFPE sections (failure rate: 0%). Patients with negative sentinel nodes in frozen sections but micrometastasis in FFPE sections had no lymph node recurrence during the follow-up period (0%, 0/6). However, in cases with tumor-positive nodes in frozen sections, metastases in non-sentinel basins were detected in the paraffin blocks (8.3%, 2/24). CONCLUSIONS: The single-section HE staining method is sufficient for detecting macrometastasis via intraoperative pathological examination. If a negative frozen-section result is confirmed, sentinel basin dissection can be performed safely. Otherwise, standard surgery is required.
Assuntos
Estudos de Viabilidade , Metástase Linfática , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Masculino , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Feminino , Biópsia de Linfonodo Sentinela/métodos , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Metástase Linfática/patologia , Estudos Prospectivos , Gastrectomia/métodos , Idoso de 80 Anos ou mais , Adulto , Secções Congeladas/métodos , Excisão de Linfonodo/métodosRESUMO
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.
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/epidemiologiaRESUMO
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.
Assuntos
5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase , Neoplasias Colorretais , Ferredoxina-NADP Redutase , Polimorfismo de Nucleotídeo Único , Riboflavina , Humanos , Masculino , Ferredoxina-NADP Redutase/genética , Feminino , Neoplasias Colorretais/genética , Neoplasias Colorretais/epidemiologia , República da Coreia/epidemiologia , Estudos de Casos e Controles , Pessoa de Meia-Idade , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Idoso , Predisposição Genética para Doença , Fatores de Risco , AdultoRESUMO
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.
Assuntos
Neoplasias Colorretais , Dieta , Interleucina-10 , Polimorfismo de Nucleotídeo Único , Selênio , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/prevenção & controle , Interleucina-10/genética , Estudos de Casos e Controles , Masculino , Selênio/administração & dosagem , Feminino , Pessoa de Meia-Idade , República da Coreia , Idoso , Fatores de Risco , Alelos , Predisposição Genética para Doença , GenótipoRESUMO
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.
Assuntos
Neoplasias Colorretais , Magnésio , Receptor de Insulina , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos CD/genética , Povo Asiático/genética , Estudos de Casos e Controles , Neoplasias Colorretais/genética , Predisposição Genética para Doença , Magnésio/administração & dosagem , Razão de Chances , Polimorfismo de Nucleotídeo Único , Receptor de Insulina/genética , República da Coreia , Fatores de RiscoRESUMO
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/epidemiologiaRESUMO
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.
Assuntos
Receptor 2 de Folato , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Estudo de Associação Genômica Ampla , República da Coreia/epidemiologia , Receptor 2 de Folato/genéticaRESUMO
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
RESUMO
Perilla is a key component of Korean food. It contains several plant-specialized metabolites that provide medical benefits. In response to an increased interest in healthy supplement food from the public, people are focusing on the properties of Perilla. Nevertheless, unlike rice and soybeans, there are few studies based on molecular genetics on Perilla, so it is difficult to systematically study the molecular breed. The wild Perilla, Perilla citriodora 'Jeju17', was identified a decade ago on the Korean island of Jeju. Using short-reads, long-reads, and Hi-C, a chromosome-scale genome spanning 676 Mbp, with high contiguity, was assembled. Aligning the 'Jeju17' genome to the 'PC002' Chinese species revealed significant collinearity with respect to the total length. A total of 31,769 coding sequences were predicted, among which 3331 were 'Jeju17'-specific. Gene enrichment of the species-specific gene repertoire highlighted environment adaptation, fatty acid metabolism, and plant-specialized metabolite biosynthesis. Using a homology-based approach, genes involved in fatty acid and lipid triacylglycerol biosynthesis were identified. A total of 22 fatty acid desaturases were found and comprehensively characterized. Expression of the FAD genes in 'Jeju17' was examined at the seed level, and hormone signaling factors were identified. The results showed that the expression of FAD genes in 'Jeju17' at the seed level was high 25 days after flowering, and their responses of hormones and stress were mainly associated with hormone signal transduction and abiotic stress via cis-elements patterns. This study presents a chromosome-level genome assembly of P. citriodora 'Jeju17', the first wild Perilla to be sequenced from the Korean island of Jeju. The analyses provided can be useful in designing ALA-enhanced Perilla genotypes in the future.
Assuntos
Perilla , Humanos , Perilla/genética , Perilla/metabolismo , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Melhoramento Vegetal , Hormônios , República da CoreiaRESUMO
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 ZincoRESUMO
High-quality molecular markers are essential for marker-assisted selection to accelerate breeding progress. Compared with diploid species, recently diverged polyploid crop species tend to have highly similar homeologous subgenomes, which is expected to limit the development of broadly applicable locus-specific single-nucleotide polymorphism (SNP) assays. Furthermore, it is particularly challenging to make genome-wide marker sets for species that lack a reference genome. Here, we report the development of a genome-wide set of kompetitive allele specific PCR (KASP) markers for marker-assisted recurrent selection (MARS) in the tetraploid minor crop perilla. To find locus-specific SNP markers across the perilla genome, we used genotyping-by-sequencing (GBS) to construct linkage maps of two F2 populations. The two resulting high-resolution linkage maps comprised 2326 and 2454 SNP markers that spanned a total genetic distance of 2133 cM across 16 linkage groups and 2169 cM across 21 linkage groups, respectively. We then obtained a final genetic map consisting of 22 linkage groups with 1123 common markers from the two genetic maps. We selected 96 genome-wide markers for MARS and confirmed the accuracy of markers in the two F2 populations using a high-throughput Fluidigm system. We confirmed that 91.8% of the SNP genotyping results from the Fluidigm assay were the same as the results obtained through GBS. These results provide a foundation for marker-assisted backcrossing and the development of new varieties of perilla.
Assuntos
Perilla , Tetraploidia , Genótipo , Perilla/genética , Polimorfismo de Nucleotídeo Único/genética , Melhoramento Vegetal , Ligação Genética , Genoma de Planta/genéticaRESUMO
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 RiscoRESUMO
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.