Human cytomegalovirus lytic infection inhibits replication-dependent histone synthesis and requires stem loop binding protein function.

Replication-dependent (RD) histones are deposited onto human cytomegalovirus (HCMV) genomes at the start of infection. We examined how HCMV affects the de novo production of RD histones and found that viral infection blocked the accumulation of RD histone mRNAs that normally occurs during the S phase. Furthermore, RD histone mRNAs present in HCMV-infected cells did not undergo the unique 3' processing required for their normal nuclear export and translation. The protein that orchestrates processing in the nucleus, stem loop­binding protein (SLBP), was found predominantly in the cytoplasm, and RD histone proteins were not de novo synthesized in HCMV-infected cells. Intriguingly, however, we found that SLBP was required for the efficient synthesis and assembly of infectious progeny virions. We conclude that HCMV infection attenuates RD histone mRNA accumulation and processing and the de novo protein synthesis of the RD histones, while utilizing SLBP for an alternative purpose to support infectious virion production.

Exosome-mediated secretion of miR-127-3p regulated by RAB27A accelerates metastasis in renal cell carcinoma.

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.

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.

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.

Feasibility of intraoperative pathologic examination for sentinel lymph nodes during sentinel node navigation surgery in early gastric cancer: results of pathologic protocol for SENORITA trial.

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.

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.

Association between dietary carotenoid intake and breast cancer risk: a case-control study among Korean women.

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.

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.

Development of an SNP marker set for marker-assisted backcrossing using genotyping-by-sequencing in tetraploid perilla.

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.

Interaction between dietary potassium intake and TNF-α rs1800629 genetic polymorphism in gastric cancer risk: a case-control study conducted in Korea.

Mineral consumption has been suggested to have an impact on gastric cancer (GC) prevention. However, the protective effect of potassium against gastric carcinogenesis remains inconclusive. The causal link between inflammation and cancer is well established. Notably, potassium intake and potassium channels may play certain roles in regulating the production of TNF-α (TNF-α). We aimed to determine whether dietary potassium intake is related to the risk of GC. We further observed whether this association was modified by TNF-α rs1800629. We designed a case-control study comprising 377 GC cases and 756 controls. Information on dietary potassium intake was collected using a semiquantitative food frequency questionnaire. Genotyping was performed by the Affymetrix Axiom Exom 319 Array platform. Unconditional logistic regression models were used to assess associations. A significantly reduced GC risk was found for those who consumed higher dietary potassium levels (OR = 0·63, 95 % CI = 0·45, 0·89, P for trend = 0·009). In the dominant model, we observed a non-significant association between TNF-α rs1800629 and GC risk (OR = 1·01, 95 % CI = 0·68, 1·49). In females, those who were homozygous for the major allele (G) of rs1800629 with a higher intake of dietary potassium exhibited a decreased risk of GC (OR = 0·40, 95 % CI = 0·20, 0·78, P interaction = 0·041). This finding emphasises the beneficial effect of potassium intake on GC prevention. However, this association could be modified by TNF-α rs1800629 genotypes. A greater protective effect was exhibited for females with GG homozygotes and high potassium intake.

Vitamin E intake and paraoxonase 1 (PON1) rs662 genetic polymorphism are associated with colorectal cancer risk in a Korean population.

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.

Coffee consumption and its interaction with the genetic variant AhR rs2066853 in colorectal cancer risk: a case-control study in Korea.

The bioactive compounds in coffee have several antioxidant properties that may beneficially impact colorectal cancer (CRC) development. The aryl hydrocarbon receptor (AhR) is an important transcription factor that regulates an enzyme related to the caffeine metabolism pathway. We investigated the modification effect on coffee of AhR gene polymorphism in the risk of CRC. A case-control study was conducted with 699 cases and 1393 controls to investigate the interaction between coffee intake and the AhR rs2066853 variant in CRC risk. The odds ratios (ORs) and 95% confidence intervals (CIs) were assessed using multiple logistic regression analyses. We observed a significant protective effect of coffee against CRC in the overall and male populations. Consuming three or more cups of coffee per day may significantly lower CRC risk in all subjects by 77% and in men by 83% (OR = 0.23, 95% CI: 0.14-0.39 and OR = 0.17, 95% CI: 0.09-0.34, respectively, P-trends < 0.001). No association between AhR rs2066853 and CRC risk was found. In the dominant model, the G/G genotype had a strongest synergistic effect with coffee on protection against CRC (OR = 0.12, 95% CI: 0.06-0.26, P-interaction = 0.014). The interaction remained significant in men and the distal colon cancer subgroup. In the additive model, the interaction was clearly shown strongest in G/G carriers (OR = 0.12, 95% CI: 0.06-0.27, P-interaction = 0.039), followed by A/A and G/A carriers. The interaction remained significant in men and the rectal cancer subgroup. In conclusion, the protective effect of coffee on CRC risk might interact with the genetic variant AhR rs2066853, and this joint effect was determined by sex and site-specific cancer.

Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer.

TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor (EGFR) and cyclin D1 were assessed in 96 tissue samples, including non-tumorous tissue, adenoma, and carcinoma. Then, the prognostic impact of EGFR and cyclin D1 was retrospectively investigated in 316 patients who underwent R0 resection for GC. EGFR positivity increased as gastric tissue became malignant, and cyclin D1 positivity was increased in all the tumorous tissues. However, there was no survival difference caused by the EGFR positivity, while the cyclin D1-postive group had worse overall survival (OS) than the cyclin D1-negative group in stage I GC (10-year survival rate (10-YSR): 62.8% vs. 86.5%, p = 0.010). In subgroup analyses for the propensity score-matched (PSM) cohort, there were also significant differences in the OS according to the cyclin D1 positivity in stage I GC but not in stage II and III GC. Upon multivariate analysis, cyclin D1 positivity was an independent prognostic factor in stage I GC. In conclusion, cyclin D1 may be a useful biomarker for predicting prognosis in stage I GC.

Association between metabolic syndrome and its components and incident colorectal cancer in a prospective cohort study.

BACKGROUND: Metabolic syndrome (MetS) has been identified as a contributor to cancer development. However, reports concerning the association between MetS and colorectal cancer (CRC) have been inconsistent. This study investigated whether MetS, its components, and the number of components increase the risk of CRC. METHODS: This was a prospective cohort study of 41,837 participants recruited from August 2002 to December 2014 from the National Cancer Center in South Korea. The participants were followed until December 2017 to identify incident CRC cases. The participants underwent laboratory tests at the baseline. Additionally, a self-administered questionnaire collected information concerning lifestyle and general characteristics at the baseline. A Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to explore the association between MetS and its components and CRC risk after adjustments for confounding variables. RESULTS: In total, 128 incident CRC cases were identified during the follow-up period. An increased CRC risk was found among participants with MetS (HR, 1.63; 95% CI, 1.08-2.44). Additionally, elevated blood pressure (HR, 1.50; 95% CI, 1.05-2.15) and a high fasting glucose level (HR, 1.80; 95% CI, 1.23-2.63) were associated with an elevated risk of CRC. Notably, an increased risk was identified among participants with abdominal obesity coexisting with another component of MetS. CONCLUSIONS: These results suggest that MetS is a risk factor for CRC. Greater emphasis should be placed on the importance of CRC screening among individuals with abdominal obesity coexisting with another component of MetS. LAY SUMMARY: Colorectal cancer (CRC) ranks as the third most common cancer type in terms of incidence. Metabolic syndrome (MetS) has been identified as a contributor to cancer development. However, the association between MetS and CRC remains controversial because of a lack of consistent findings in previous studies. In this study, the National Cholesterol Education Program's Adult Treatment Panel III guidelines are used for the diagnosis of MetS. MetS is found to be a predictor of CRC. Additionally, the importance of CRC screening among individuals with 2 components of MetS should be emphasized.

Interactive effect of the empirical lifestyle index for insulin resistance with the common genetic susceptibility locus rs2423279 for colorectal cancer.

The aim of this study is to examine the empirical insulinemic potential consisting of dietary and lifestyle factors and the interactive effect with the common genetic susceptibility locus rs2423279 on the risk of colorectal cancer (CRC). This case-control study was conducted with 923 CRC patients and 1846 controls. The empirical measures for assessing the insulinemic potential, namely, the empirical dietary index for hyperinsulinemia (EDIH), for insulin resistance (EDIR), the empirical lifestyle index for hyperinsulinemia (ELIH), and for insulin resistance (ELIR), were calculated based on semiquantitative food frequency questionnaire and lifestyle questionnaire. A genetic variant of rs2423279 was genotyped. The CRC patients were more likely to score in the highest quartile for the ELIH (OR 2·90, Q4 v. Q1, 95 % CI (2·01, 4·19), Pfor trend < 0·001), EDIR (OR 3·32, Q4 v. Q1, 95 % CI (2·32, 4·74), P < 0·001) and ELIR (OR 2·79, Q4 v. Q1, 95 % CI (1·96, 3·97), P < 0·001) than the controls. The significant effect between the ELIR, which assesses dietary and lifestyle patterns related to insulin resistance, and C allele carriers of rs2423279 was stronger than that for homozygous T allele carriers (OR 2·50, 95 % CI (1·78, 3·51), Pfor interaction = 0·034). The empirical insulinemic potential for insulin resistance might have interactive effects with the rs2423279 polymorphism on the risk of CRC. The results of this study suggest the basis of the metabolic impact of the insulin response on colorectal carcinogenesis.

Riboflavin intake, MTRR genetic polymorphism (rs1532268) and gastric cancer risk in a Korean population: a case-control study.

The vitamin B group, including riboflavin, plays paramount roles in one-carbon metabolism (OCM), and disorders related to this pathway have been linked to cancer development. The variants of genes encoding OCM enzymes and the insufficiency of B vitamins could contribute to carcinogenesis. Very few observational studies have revealed a relationship between riboflavin and gastric cancer (GC), especially under conditions of modified genetic factors. We carried out a study examining the association of riboflavin intake and its interaction with MTRR (rs1532268) genetic variants with GC risk among 756 controls and 377 cases. The OR and 95 % CI were evaluated using unconditional logistic regression models. We observed protective effects of riboflavin intake against GC, particularly in the female subgroup (OR = 0·52, 95 % CI 0·28, 0·97, Ptrend = 0·031). In the MTRR (rs1532268) genotypes analysis, the dominant model showed that the effects of riboflavin differed between the CC and CT + TT genotypes. Compared with CC carriers, low riboflavin intake in T+ carriers was significantly associated with a 93 % higher GC risk (OR = 1·93, 95 % CI 1·09, 3·42, Pinteraction = 0·037). In general, higher riboflavin intake might help reduce the risk of GC in both CC and TC + TT carriers, particularly the T+ carriers, with marginal significance (OR = 0·54, 95 % CI 0·28, 1·02, Pinteraction = 0·037). Our study indicates a protective effect of riboflavin intake against GC. Those who carry at least one minor allele and have low riboflavin intake could modify this association to increase GC risk in the Korean population.

Association between dietary intake networks identified through a Gaussian graphical model and the risk of cancer: a prospective cohort study.

PURPOSE: In this study, we aimed to investigate the association between dietary communities identified by a Gaussian graphical model (GGM) and cancer risk. METHODS: We performed GGM to identify the dietary communities in a Korean population. GGM-derived communities were then scored and investigated for their association with cancer incidence in the entire population as well as in the 1:1 age- and sex-matched subgroup using a Cox proportional hazards model. In the sensitivity analysis, GGM-derived communities were compared to dietary patterns (DPs) that were identified by principal component analysis (PCA) and reduced rank regression (RRR). RESULTS: During a median time to follow-up of 6.6 years, 397 cancer cases were newly diagnosed. The GGM identified 17 and 16 dietary communities for the total and matched populations, respectively. For each one-unit increase in the standard deviation of the community-specific score of the community that was composed of dairy products and bread, there was a reduced risk of cancer according to the fully adjusted model (HR: 0.80, 95% CI: 0.66-0.96). In the matched population, the third tertile of the community-specific score of the community composed of poultry, seafood, bread, cakes and sweets, and meat by-products showed a significantly reduced risk of cancer compared to that of the lowest tertile in the fully adjusted model (HR: 0.66, 95% CI: 0.50-0.86, p-trend = 0.002). CONCLUSION: We found that the GGM-identified community composed of dairy products and bread showed a reduced risk of cancer. Further population-based prospective studies should be conducted to examine possible associations of dietary intake and specific cancer types.

Dietary methyl donor nutrients, DNA mismatch repair polymorphisms, and risk of colorectal cancer based on microsatellite instability status.

PURPOSE: Colorectal cancer (CRC) is a heterogeneous disease caused by complex interplay among the diet, the environment, and genetics involving numerous molecules and pathological pathways. This study aimed to determine whether methyl donor nutrients are associated with CRC and how these associations are altered by DNA mismatch repair (MMR) genes. METHODS: In total, 626 cases and 838 age- and sex-matched controls were recruited for this case-control study. A validated food frequency questionnaire was used to assess seven methyl donor nutrients (vitamin B2, niacin, B6, folate, B12, methionine, and choline). MMR polymorphisms were genotyped using an Illumina MEGA-Expanded Array. For the 626 patients, the microsatellite instability status and immunohistochemical expression of MMR proteins were analyzed. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among the methyl donor nutrients, B2, niacin, B6, folate, and methionine were inversely associated with CRC risk, while a high intake of choline increased CRC. Regarding MMR genes, three hMSH3 polymorphisms (rs32952 A > C, rs41097 A > G, and rs245404 C > G) reduced CRC risk. Regarding gene-diet interactions, a stronger interaction effect was observed in G allele carriers of hMSH3 rs41097 with high niacin intake than in AA carriers with low niacin intake (OR, 95% CI = 0.49, 0.33-0.72, P for interaction = 0.02) in subgroups of patients with distal colon cancer (P for interaction = 0.008) and MMR proficiency with microsatellite stability (P for interaction = 0.021). CONCLUSIONS: Methyl donor nutrients may affect CRC risk leading to a balance in the MMR machinery.

The interaction between glycemic index, glycemic load, and the genetic variant ADIPOQ T45G (rs2241766) in the risk of colorectal cancer: a case-control study in a Korean population.

PURPOSE: The glycemic index (GI), glycemic load (GL), and adiponectin level contribute to glycemic response and insulin sensitivity in the body. Studies have shown that tumor development is related to glycemic disorders; however, the results are contradictory. We aimed to investigate the association of GI and GL with colorectal cancer (CRC) risk in a Korean population and their possible interactions with the genetic variant ADIPOQ T45G. METHODS AND RESULTS: A case-control study including 2096 participants with 695 CRC cases was conducted. The results showed that diets with high GI or GL were significantly associated with an increased risk of CRC [odds ratio (OR) = 5.44, 95% confidence interval (CI) 3.85-7.68; OR = 4.43, 95% CI 3.18-6.15, respectively; all p-trends < 0.001]. Moreover, even with a low-GI and low-GL diet, G/G genotype carriers may have 2.93-fold and 3.77-fold higher risk of rectal cancer compared to carriers of other genotypes (T/T + T/G), (OR = 2.93, 95% CI 1.01-8.59, p-interaction = 0.011 for GI; OR = 3.77, 95% CI 1.46-9.77, p-interaction = 0.025 for GL). CONCLUSIONS: Overall, our study suggests positive associations of GI and GL with CRC risk. Moreover, the associations of GI and GL with rectal cancer risk could be modified by ADIPOQ T45G in a Korean population. Further studies with larger sample sizes are needed to confirm our findings.

Diets high in glycemic index and glycemic load are associated with an increased risk of metabolic syndrome among Korean women.

BACKGROUND AND AIMS: Accurate estimation of the glycemic index (GI) and glycemic load (GL) of diets is essential when assessing health implications of dietary GI and GL. The present study aimed to estimate dietary GI and GL utilizing the updated GI tables with a large number of new, reliable GI values and assess their associations with metabolic syndrome among Korean adults. METHODS AND RESULTS: We analyzed data from 3317 men and 6191 women for this cross-sectional study. Dietary intake was assessed with a validated food frequency questionnaire. Metabolic syndrome and its components were defined based on the harmonized criteria with Korean-specific cutoffs for waist circumference. Multivariate logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Compared with women in the lowest quintiles of energy-adjusted dietary GI and GL, women in the highest quintiles had significantly greater risks of metabolic syndrome (GI, OR = 1.56, 95% CI = 1.18-2.06; GL, OR = 1.80, 95% CI = 1.27-2.57), elevated blood pressure, reduced high-density lipoprotein cholesterol (HDL-C, both GI and GL), elevated triglycerides (GI only), elevated waist circumference, and elevated fasting glucose (GL only). Among men, no significant association was noted except for a higher risk of reduced HDL-C (OR = 1.59, 95% CI = 1.01-2.29) in the highest quintile of energy-adjusted dietary GI than in the lowest quintile. CONCLUSION: Our findings suggest that dietary GI and GL are positively associated with metabolic syndrome risk among women, but not men, in Korea.