Impact of methylenetetrahydrofolate reductase polymorphisms and folate intake on the risk of gastric cancer and their association with Helicobacter pylori infection and tumor site

Abstract

ABSTRACT. Folic acid and methylenetetrahydrofolate reductase (MTHFR) may both affect the development of human cancer. We conducted a population-based case-control study in a Chinese population to investigate the potential role of folate intake and MTHFR gene polymorphisms in gastric cancer, and their interaction with infection by Helicobacter pylori and tumor location. A total of 767 patients with newly diagnosed gastric cancer and 775 controls were selected for this study. Genotyping of MTHFR C677T and A1298C was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System, and information 9719 MTHFR and folate and gastric cancer risk ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (4): 9718-9726 (2014) on folate intake was collected by questionnaire. Compared with the CC genotype of MTHFR C677T, the TT genotype was significantly associated with a decreased risk of gastric cancer when the analysis was adjusted for other potential risk factors. We found a marginal significantly decreased risk of gastric cancer for individuals carrying the T allele [adjusted odds ratio (OR) = 0.83; 95% confidence interval (CI) = 0.65-1.01]. We detected an inverse relationship between folate intake and risk of gastric cancer, and the adjusted ORs (95%CI) for moderate and high folate intake were 0.97 (0.74-1.25) and 0.64 (0.49-0.87), respectively. Moreover, H. pylori infection, folate intake, and location of the tumor showed a significant interaction with the MTHFR C677T polymorphism. Our study suggests a protective role of MTHFR 677TT and high folate intake against gastric cancer, and the effect of the MTHFR C677T genotype may differ by H. pylori infection, folate consumption, and tumor site.

Dietary folate, one‐carbon metabolism‐related genes, and gastric cancer risk in Korea

“…Our null results are consistent with previous epidemiologic studies in the Korean population . A few studies have investigated the interaction between MTHFR polymorphisms and folate intake on gastric cancer risk, but these results are also inconsistent . We found a statistically significant interaction between dietary folate intake and MTHFR G1793A, which was not previously reported.…”

“…Two common polymorphisms of MTHFR , C677T, and A1298T, reduce enzyme activity and lead to lower levels of 5‐methyl‐THF and the accumulation of 5,10‐methylene‐THF . Several studies have reported that the TT genotype of MTHFR C677T is associated with an increased gastric cancer risk , whereas other studies have shown a negative association or null results . Most studies investigating the effect of MTHFR A1298T have reported a null association with gastric cancer risk , but Vollset et al.…”

“…Other synonymous variants or other polymorphisms of one‐carbon metabolism‐related enzymes, such as dihydrofolate reductase or thymidylate synthetase could contribute to gastric cancer risk. Although a few studies have reported a strong interaction between MTHFR polymorphisms and dietary intake , total energy intake was not considered in those analyses. Adjusting for total energy intake is critical in epidemiologic studies because the effect of nutritional intake may be confounded by total energy intake .…”

“…Such inconsistent results in terms of gastric cancer might be explained by gene–diet interactions. Several studies have examined the effect modification of folate intake on genetic variants related to one‐carbon metabolism, focusing primarily on the MTHFR C677T and A1298C polymorphisms ; however, the results are still conflicting. The limited number of genetic variants included in these studies may explain the discrepancies in the results.…”

Evaluation of an Association of Blood Homocysteine Levels With Gastric Cancer Risk From 27 Case–Control Studies

“…The sensitivity analysis of individual studies by sequential removal and the control population—results were deviated from the HWE. 23 , 33 , 34 , 37 , 41 , 42 , 46 All the significance of OR did not exclude the changes after these studies, and our results were robust and reliable. Potential bias was examined by Begg's funnel plot and Egg's test.…”