Low
folate intake has been associated with an increased risk of both oesophageal and
gastric cancers.
Reduced folate carrier (RFC1, also named SLC19A1) is an essential
folate transporter and functions as a bidirectional
anion exchanger, taking up
folate cofactors and exporting various organic
anions. A G80A polymorphism in RFC1 gene has been shown to be associated with alterations in
folate and
homocysteine metabolism in healthy individuals. In this study, we hypothesised that genetic variants in RFC1 may modulate risk of oesophageal
cancer (EC) and
gastric cancer (GC). To test this hypothesis, we evaluated the associations of the G80A polymorphism of RFC1 with EC and GC risk in a case-control study of 216 EC and 633 GC cases and 673
cancer-free controls in a Chinese population. We found that compared with the 80GG/GA genotypes in the recessive model, the variant homozygote RFC1 80AA was associated with a significantly increased risk of EC (adjusted odds ratio (OR)=1.80, 95% confidence interval (CI)=1.29-2.51), GC (adjusted OR=1.59, 95% CI=1.25-2.02) and EC and GC combined (adjusted OR=1.63, 95% CI=1.30-2.04). In the dominant model, the risk associated with RFC1 80AA was also elevated in EC (OR=1.35, 95% CI=0.91-1.99), GC (OR=1.43, 95% CI=1.07-1.91) and EC and GC combined (adjusted OR=1.40, 95% CI=1.07-1.83), compared with the 80GG genotype. The stratification analyses showed that effects of the RFC1 80AA genotype were more evident in subgroups of relatively older (60 years), female, non-smokers, and non-drinkers both in EC and GC. Although the exact
biological mechanism of this association remains to be explored, our findings suggest possible involvement of RFC1 variant in the susceptibility of EC and GC. Further large and functional studies are needed to confirm our findings.