title: Reduced folate carrier gene G80A polymorphism is associated with an increased risk of gastroesophageal cancers in a Chinese population.
abstract: 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.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Cancer Research Center, Nanjing Medical University, 140 Hanzhong Road, Nanjing, and Yixing People's Hospital, Yixing City, Jiangsu 210029, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Wensen
authors.initials: W
authors.lastname: Chen
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Tan
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Weiliang
authors.initials: W
authors.lastname: Ding
authors.forename: Zhaolai
authors.initials: Z
authors.lastname: Hua
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.forename: Yaochu
authors.initials: Y
authors.lastname: Xu
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D058978:Reduced Folate Carrier Protein; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human