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Volume 45, Issue 10 , Pages 1824-1830, July 2009

Genetic variation in sodium-dependent ascorbic acid transporters and risk of gastric cancer in Poland

Margaret E. Wright
- Department of Pathology, University of Illinois at Chicago, 840 S Wood St., CSN 130, Chicago, IL 60612, USA
- Corresponding author: Tel.: +1 312 996 9684; fax: +1 312 996 4812.
Gabriella Andreotti
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA
Jolanta Lissowska
- Department of Cancer Epidemiology and Prevention, The M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland
Meredith Yeager
- Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, NIH, DHHS, Gaithersburg, MD 20892, USA
Witold Zatonski
- Department of Cancer Epidemiology and Prevention, The M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland
Stephen J. Chanock
- Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, NIH, DHHS, Gaithersburg, MD 20892, USA
Wong-Ho Chow
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA
Lifang Hou
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA

Received 5 December 2008; received in revised form 15 January 2009; accepted 22 January 2009. published online 26 February 2009.

Abstract

Higher ascorbic acid consumption is associated with a reduced risk of gastric cancer in numerous epidemiologic studies. We investigated whether single nucleotide polymorphisms (SNPs) in SLC23A1 and SLC23A2 – genes that encode key ascorbic acid transport proteins – affect gastric cancer risk in 279 incident cases and 414 age- and gender-matched controls drawn from a population-based case–control study in Poland. Compared to subjects who were homozygous for the common G allele of the SLC23A2 SNP rs12479919, carriers of the AA genotype had a 41% lower risk of gastric cancer [odds ratio (OR)=0.59, 95% confidence interval (CI): 0.36–0.95; P trend=0.06]. A haplotype that contained the common allele of the rs6139591, rs2681116 and rs14147458 SNPs in SLC23A2 was also significantly inversely associated with gastric malignancy. No other polymorphisms in either gene were related to risk, and there was no effect modification by ascorbic acid intake. These findings suggest that genetic variation in SLC23A2 impacts gastric cancer risk, although confirmation in other studies is required.