Impact of Dietary Nut and DNA Methyltransferase 1 rs16999593 Polymorphism on Gastric Cancer Risk: Evidence from a Korean Hospital-Based Case-Control Study.

BACKGROUND

Both genetic and epigenetic changes, particularly deoxyribonucleic acid (DNA) methylation, play crucial roles in gastric cancer development. Nuts, highlighted for their anti-inflammatory effects, may help maintain proper DNA methylation patterns. Thus, we hypothesized that high intake of nuts may interact with the DNA methylation-related genetic factor, DNA methyltransferase 1 (DNMT1) rs16999593 polymorphism in gastric cancer risk.

OBJECTIVES

We aimed to investigate the interaction between dietary nut consumption and DNMT1 rs16999593 polymorphism, exploring their combined effects on gastric cancer risk.

METHODS

This case-control study at the National Cancer Center in Korea investigated the impact of nut consumption and DNMT1 rs16999593 polymorphism on gastric cancer risk, involving 1245 participants. Genetic analysis and dietary intake assessment were performed. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS

High nut consumption was strongly associated with reduced risk of gastric cancer among women (adjusted OR: 0.42; 95% CI: 0.20, 0.87; P for trend = 0.026 for ≥3 servings/wk group vs. none). The dominant model of DNMT1 rs16999593 exhibited an inverse trend in gastric cancer risk (total: OR: 0.75; 95% CI: 0.54, 1.05), although not statistically significant. However, those with high nut consumption and homozygous for the major allele (T) showed lower gastric cancer risk, with significant interaction in overall (OR: 0.52; 95% CI: 0.27, 1.01; P-interaction = 0.045) and in women (OR: 0.17; 95% CI: 0.05, 0.57; P-interaction = 0.001).

CONCLUSIONS

Our study demonstrates a significant inverse association between nut consumption and gastric cancer risk, particularly in women. On a multiplicative scale, our findings highlight the potential negative interactions between nut consumption and DNMT1 rs16999593 genetic polymorphism in gastric cancer risk in the total population and in women.