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Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, whose role in gastric carcinogenesis is controversial. The authors performed a meta-analysis and individual data pooled analysis of case-control studies that examined the association between C677T and A1298C polymorphisms (the former being associated with low folate serum levels) and gastric cancer (meta-analyses: 16 studies, 2,727 cases and 4,640 controls for C677T and seven studies, 1,223 cases and 2,015 controls for A1298C; pooled analyses: nine studies, 1,540 cases and 2,577 controls for C677T and five studies, 1,146 cases and 1,549 controls for A1298C). An increased risk was found for MTHFR 677 TT in the meta-analysis (odds ratio (OR) = 1.52, 95% confidence interval (CI): 1.31, 1.77) and pooled analysis (OR = 1.49, 95% CI: 1.14, 1.95). No association resulted for MTHFR 1298 CC (meta-OR = 0.94, 95% CI: 0.65, 1.35; pooled OR = 0.90, 95% CI: 0.69, 1.34). Results from the pooled analysis of four studies on C677T stratified according to folate levels showed an increased risk for individuals with low (OR = 2.05, 95% CI: 1.13, 3.72) versus high (OR = 0.95, 95% CI: 0.54, 1.67) folate levels. Overall, these findings support the hypothesis that folate plays a role in gastric carcinogenesis.

Every year approximately 3 million Europeans develop a cancer. Of these patients, 20-25% will suffer from cancer of the hepatogastrointestinal tract (the largest cancer group) and most of these individuals will die from the disease. Recent analysis from the American Cancer Society indicates that disease-related mortality from heart, cerebrovascular and infectious disease has decreased dramatically in the last 60 years, whereas the mortality of cancer remains unchanged. Despite recent improvements in the understanding of the biology, development and progression of human cancers, and the development of novel diagnostic and therapeutic approaches, most cancer patients are diagnosed in an advanced stage with a limited chance of cure. We hypothesize that there has been a dramatic shift in the treatment and, more importantly, prevention of heart, cerebrovascular and infectious diseases that has not yet reached oncology practice. We think that the shift from local to systemic therapy in combination with biomarker-guided detection of patients at risk leads to a reversion of current medical management: we do not treat the end-stage disease but rather follow the course of cancer development starting with risk assessment, followed by disease treatment and prevention of disease progression. Thus, we can prevent end-stage disease that cannot be treated curatively. Our two-step hypothesis should lead to a dramatic improvement of the prognosis of cancer patients.