Impact of Methylenetetrahydrofolate Reductase C677T Polymorphism on the Risk of Gastric Cancer and Its Interaction with Helicobacter pylori Infection

Authors
Samaneh Saberi
Kazem Zendehdel
Sahar Jahangiri
Yeganeh Talebkhan
Afshin Abdirad
Nazanin Mohajerani
Maryam Bababeik
Najmeh Karami
Maryam Esmaili
Akbar Oghalaie
Parisa Hassanpour
Neda Amini
Mohammad Ali Mohagheghi
Mahmoud Eshagh Hossieni
Marjan Mohammadi
10.6091/ibj.1102.2012
Abstract
Background: Attempts for early detection of gastric cancer have recently focused on host's genetic susceptibility factors and gene-environment interactions. We have, herein, studied the association of MTHFR C677T single nucleotide polymorphism (SNP) and its interaction with Helicobacter pylori infection, smoking, age and gender on the risk of gastric cancer among an Iranian population. Methods: Gastric cancer patients (n = 450) and cancer-free controls (n = 780) were studied for serum H. pylori-specific IgG antibodies by ELISA and MTHFR C677T polymorphism (SNP) by PCR-RFLP. Demographic and life style data were collected through patient interviews. Unconditional logistic regression model estimated odds ratio (OR) and the corresponding 95% confidence intervals (CI). Results: The interactions of MTHFR genotype with H. pylori infection (P = 0.03), age (P = 0.049) and gender (P = 0.007) were statistically significant. Accordingly, MTHFR C677T carriers who were also positive for H. pylori infection exhibited 80% (OR = 1.8, 95% CI = 1.0-2.9) significant excess risk of non-cardia gastric cancer. Furthermore, subjects over the age of 50 or female subjects carrying MTHFR C677T SNP showed 40 (OR = 1.4, 95% CI = 1.0-2.0) and 100 (OR = 2.0, 95% CI = 1.2-3.2) percent increased risk of gastric cancer, respectively. Conclusion: Therefore, MTHFR C677T SNP seems to increase the risk of gastric cancer and the effect is significantly inflated by interactions with H. pylori infection, age and gender.
Keywords
Helicobacter pylori
Smoking
Gender Identity
Age group
Methylenetetrahydrofolate reductase