Multiple studies have reported an association between disturbances of
folate metabolism and increased risk of
gastric cancer, including low intake of
folate, low levels of
folate in blood or genetic factors affecting
folate metabolism. Among the genetic factors, in particular a common polymorphism in the gene encoding for
5,10-methylenetetrahydrofolate reductase (MTHFR C677T) has been linked to
gastric cancer. Other polymorphisms in
folate-metabolising genes have been less frequently investigated. Therefore, we analyzed this polymorphism, the
glutamate carboxypeptidase (GCP) II C1561T and the
reduced folate carrier (RFC) G80A in a case-control study involving 106 patients with histologically confirmed and characterized
gastric cancer with adjustment for other established risk factors for
gastric cancer in comparison to 106 age- and sex-matched controls. Neither the MTHFR nor the GCP gene polymorphisms showed an association to
cancer diagnosis, to
tumor stage, grade of differentiation or Lauren type. However, non-cardia
cancers were more likely to exhibit the 80GA and 80AA RFC genotypes, compared to
cancers of the gastric cardia (adjusted OR 0.28; 95% CI=0.11-0.71). Thus, gene polymorphisms of the RFC gene might contribute to an increased risk of developing distal
gastric cancer.