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.

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.

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.

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

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

A comparison of machine learning models and Cox proportional hazards models regarding their ability to predict the risk of gastrointestinal cancer based on metabolic syndrome and its components.

Background: Little is known about applying machine learning (ML) techniques to identify the important variables contributing to the occurrence of gastrointestinal (GI) cancer in epidemiological studies. We aimed to compare different ML models to a Cox proportional hazards (CPH) model regarding their ability to predict the risk of GI cancer based on metabolic syndrome (MetS) and its components. Methods: A total of 41,837 participants were included in a prospective cohort study. Incident cancer cases were identified by following up with participants until December 2019. We used CPH, random survival forest (RSF), survival trees (ST), gradient boosting (GB), survival support vector machine (SSVM), and extra survival trees (EST) models to explore the impact of MetS on GI cancer prediction. We used the C-index and integrated Brier score (IBS) to compare the models. Results: In all, 540 incident GI cancer cases were identified. The GB and SSVM models exhibited comparable performance to the CPH model concerning the C-index (0.725). We also recorded a similar IBS for all models (0.017). Fasting glucose and waist circumference were considered important predictors. Conclusions: Our study found comparably good performance concerning the C-index for the ML models and CPH model. This finding suggests that ML models may be considered another method for survival analysis when the CPH model's conditions are not satisfied.

Influence of Fasting Glucose Level on Gastric Cancer Incidence in a Prospective Cohort Study.

BACKGROUND: High fasting glucose has been indicated in relation to a higher risk of gastric cancer, but the majority of studies have focused on diabetes (fasting glucose ≥126 mg/dL). Here, we investigated whether fasting glucose levels, including prediabetic and diabetic levels, influence gastric cancer incidence. METHODS: A prospective study was conducted with 41,837 participants aged 16 and older who underwent health examinations at the National Cancer Center in South Korea from August 2002 to December 2014. Participants were followed up until December 2017 to identify incident gastric cancer cases. A fasting glucose test was performed based on venous blood samples taken from participants after 8 hours of fasting. We used the Cox proportional hazards regression model to explore the association of fasting glucose levels with gastric cancer incidence. RESULTS: We identified 263 incident gastric cancer cases during the follow-up period. A significant association of high fasting glucose with gastric cancer incidence was found for postmenopausal women [hazard ratio (HR) = 1.88; 95% confidence interval (CI) = 1.11-3.20]. There was also a significant association between high fasting glucose and gastric cancer incidence among all participants who were nonsmokers (HR = 1.89; 95% CI = 1.21-2.95), had a BMI < 25 kg/m2 (HR = 1.45; 95% CI = 1.00-2.12), and did not have a first-degree family history of gastric cancer (HR = 1.45; 95% CI = 1.06-1.99). CONCLUSIONS: Our findings support that high fasting glucose is a risk factor for gastric cancer development in postmenopausal women. IMPACT: Our results provide evidence for future planning and management regarding cancer prevention.

The Associations of Dietary Iron Intake and the Transferrin Receptor (TFRC) rs9846149 Polymorphism with the Risk of Gastric Cancer: A Case-Control Study Conducted in Korea.

BACKGROUND: A positive association between a high iron intake and colorectal cancer has been identified; however, the effect of dietary iron on gastric cancer (GC) remains unclear. Here, we investigate whether dietary iron is related to GC risk and whether the transferrin receptor (TFRC) rs9846149 polymorphism modifies this association. METHODS: A case-control study was designed to assess this association among 374 GC patients and 754 healthy controls. A self-administered questionnaire was used to collect information on demographics, medical history and lifestyle. Dietary iron intake was assessed using a semi-quantitative food frequency questionnaire. TFRC rs9846149 was genetically analyzed using the Affymetrix Axiom Exom 319 Array platform. RESULTS: A higher total dietary iron was significantly associated with decreased GC risk [OR = 0.65 (0.45-0.94), p for trend = 0.018]. A similar association was observed with nonheme iron [OR = 0.64 (0.44-0.92), p for trend = 0.018]. Individuals with a major allele of TFRC rs9846149 (CC/GC) and higher intake of total iron had a significantly lower GC risk than those with a lower intake [OR = 0.60 (0.41-0.88), p interaction = 0.035]. CONCLUSION: Our findings show the protective effects of total dietary iron, especially nonheme iron, against GC risk, and this association can be modified by TFRC rs9846149.