期刊
GENES AND NUTRITION
卷 8, 期 6, 页码 549-560出版社
BMC
DOI: 10.1007/s12263-013-0346-6
关键词
Gastric cancer; Vitamin C; Antioxidants; Genetic susceptibility; SLC23A1; SLC23A2
资金
- Health Research Fund (FIS) of the Spanish Ministry of Health [Exp P10710130, La Caixa (BM 06-130), RTICC-RD06/0020/0091, RTICC-RD12/0036/0018]
- Regional Governments of Andalucia, Asturias, Basque Country, Murcia [6236]
- Navarra
- Catalan Institute of Oncology (Spain)
- Danish Cancer Society (Denmark)
- Ligue contre le Cancer
- Institut Gustave Roussy
- Mutuelle Generale de l'Education Nationale
- Institut National de la Sante et de la Recherche Medicale (INSERM) (France)
- Deutsche Krebshilfe
- Deutsches Krebsforschungszentrum
- Federal Ministry of Education and Research (Germany)
- Hellenic Health Foundation (Greece)
- Italian Association for Research on Cancer (AIRC)
- National Research Council (Italy)
- Dutch Ministry of Public Health
- Welfare and Sports (VWS)
- Netherlands Cancer Registry (NKR)
- LK Research Funds
- Dutch Prevention Funds
- Dutch ZON (Zorg Onderzoek Nederland)
- World Cancer Research Fund (WCRF)
- Statistics Netherlands (The Netherlands)
- Swedish Cancer Society
- Swedish Scientific Council
- Regional Government of Skane and Vasterbotten (Sweden)
- Cancer Research UK
- Medical Research Council (United Kingdom)
- Cancer Research UK [14136] Funding Source: researchfish
- Medical Research Council [G0401527, G1000143] Funding Source: researchfish
Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20 polymorphisms in vitamin C transporter genes SCL23A1 and SCL23A2 and GC risk in 365 cases and 1,284 controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. We also evaluated the association between these polymorphisms and baseline plasma vitamin C levels in a subset of participants. Four SNPs were predictors of plasma vitamin C levels (SLC23A1 rs11950646 and rs33972313; SLC23A2 rs6053005 and rs6133175) in multivariable linear regression models. One SNP (SLC23A2 rs6116569) was associated with GC risk, in particular non-cardia GC (OR = 1.63, 95 % CI = 1.11-2.39, based on 178 non-cardia cases), but this association was attenuated when plasma vitamin C was included in the logistic regression model. Haplotype analysis of SLC23A1 yielded no associations with GC. In SLC23A2, one haplotype was associated with both overall and non-cardia GC, another haplotype was associated with GC overall, and a third was associated with intestinal-type GC. Common variants in SLC23A1 and SLC23A2 may influence plasma vitamin C concentration independent of dietary intake, and variation in SLC23A2 may influence GC risk. Additional prospective studies in large populations and consortia are recommended. Investigation of variation in vitamin C transporter genes may shed light on the preventative properties of vitamin C in gastric carcinogenesis.
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