TNF genetic polymorphism (rs1799964) may modify the effect of the dietary inflammatory index on gastric cancer in a case–control study

Abstract

The inflammatory process is known to increase the risk of gastric carcinogenesis, and both genetic and dietary factors are associated with inflammation. In the present study of 1,125 participants (373 cases and 752 controls), we determined whether the dietary inflammatory index (DII) is associated with the risk of gastric cancer (GC) and investigated whether a TNF polymorphism (rs1799964) modifies this association. Semi-quantitative food frequency questionnaire derived data were used to calculate the DII scores. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic models adjusted for confounders. When we stratified the data by sex, the association between GC and the DII was significant only among the women (OR, 2.27; 95% CI 1.25-4.19), and the DII effect on the risk of GC differed depending on the TNF genotype (OR, 2.30; 95% CI 1.27-4.24 in TT genotype; OR, 0.78; 95% CI 0.37-1.65 in CC + CT, p for interaction = 0.035). Furthermore, the association between the DII and GC was significant in the Helicobacter pylori-positive group; similarly, the effect differed based on the TNF genotype (OR, 1.76; 95% CI 1.13-2.73 in TT genotype; OR,0.98; 95% CI 0.54-1.77 in CT + CC, p for interaction = 0.034). In conclusion, rs1799964 may modify the effect of the DII on GC. According to the GLOBOCAN results reported in 2018, gastric cancer (GC) is the fifth most common cancer worldwide, and the highest mortality rates are found in East Asia, including Korea 1. In 2016, the incidence of GC was first and second among all types of cancer in Korea 2. Such a high prevalence of GC may be attributed to Helicobacter pylori infection and chronic inflammation caused by chronic gastritis 3. The inflammatory process is caused by cytokine secretion and increases the risk of the development of gastric carcinogenesis 4,5. Among these cytokines, tumor necrosis factor (TNF) is among the most important factors inhibiting gastric acid secretion, causing the development of GC 6. TNF production is generally regulated at the transcriptional level 6. Polymorphisms located in the promoter region of the TNF gene affect the level of TNF. Indeed, genetic polymorphisms of the TNF gene have been proposed as candidate risk factors for GC 7. However, the results of studies investigating the association between TNF genetic polymorphism and GC risk have been inconsistent 8,9. These results indicate the need for further studies considering other factors, such as individual lifestyle factors. Environmental factors and host genetic factors also contribute to the chronic inflammatory response. Among these factors, dietary components contain both carcinogens and anticancer substances and are known to control the risk of cancer 10. For example, the consumption of fruits, vegetables, and beans containing antioxidants has been reported to help reduce inflammation, whereas the consumption of saturated fats, refined carbohydrates, and processed meat can cause inflammation 11,12. However, the analysis of a single food group or singl...

Pro-Inflammatory Diet as a Risk Factor for Stomach Cancer: Findings from a Multicenter Study in Central and Western China

“… 32 Furthermore, a case-control study of 1125 people found that the DII was associated with cancer risk, and the impact of DII on stomach cancer risk varied depending on TNF genotype. 33 Our research findings align with the aforementioned results, indicating that a pro-inflammatory diet can be considered a risk factor for stomach cancer.…”

“…[26][27][28][29] DII has been found to be particularly relevant to stomach diseases. [30][31][32][33] A cohort study in Korea reported that individuals in the highest quartile of DII score showed a 1.22-fold higher risk of incident stomach diseases compared to those in the lowest quartile. 30 Additionally, an Italian case-control study revealed a weak association between a pro-inflammatory diet and an increased risk of stomach cancer, as compared to an anti-inflammatory diet.…”

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

“…Higher expression of inflammatory genes was observed in females than in males due to sex hormones (45) . Thus, different eating habits and sex hormones may account for the difference in the interactive effect between males and females (46) . This interaction should be elucidated in further studies.…”

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

“…The genotyping and quality control processes have been described in previous studies [ 26 , 27 , 28 ]. Extraction of genomic DNA was performed using peripheral blood leukocytes.…”