Genetic Variation in Sodium-Dependent Vitamin C Transporters SLC23A1 and SLC23A2 and Risk of Advanced Colorectal Adenoma
Open accessAbstract
Previous observational studies suggest that vitamin C may reduce risk of colorectal cancer. Vitamin C transport is facilitated by membrane bound sodium-dependent transporters, SVCT1 (encoded by SLC23A1) and SVCT2 (encoded by SLC23A2). To investigate if common genetic variants in these two genes are associated with risk of colorectal tumor development, we conducted a case-control study of 656 Caucasian advanced distal colorectal adenoma cases and 665 Caucasian sigmoidoscopy-negative controls nested within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The analysis of common single nucleotide polymorphisms in SLC23A1 revealed no association. For SLC23A2, overall, there was no association with haplotypes, but two SNPs located in intron 8 and exon 11 could be associated (odds ratio = 0.49, 95% confidence interval = 0.25-0.95 for haplotype G-C vs. haplotype C-C). The findings should be confirmed in follow-up studies, and further investigation is required to probe the functional basis of this finding.
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Common variations of SLC23A2 are linked to decreased risk of colorectal adenocarcinoma.
“Common variations of SLC23A2 were linked to increased or decreased risk of gastric cancer depending on a discrete genotype [85,90], decreased risk of colorectal adenocarcinoma [91], HPV16-positive head and neck cancer [92], increased risk of bladder cancer [93], non-Hodgkin lymphoma [87], chronic lymphocytic leukemia [94], preterm delivery [84], open-angle glaucoma [95], and acute coronary syndrom”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [91]
The Discussion reports a possible association between an SLC23A2 haplotype and lower risk of advanced colorectal adenoma, not colorectal adenocarcinoma. The Results also report no significant association for individual genotypes, so the claim overextends the finding to a different outcome and to variations generally. (LLM, conf=0.90)
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- Authors
- Erichsen, H. C., Peters, U., Eck, P., Welch, R., Schoen, R. E., Yeager, M., Levine, M., Hayes, R. B., & Chanock, S.
- Affiliations
- National Institutes of Health (US)
- University of Washington (US)
- University of Pittsburgh (US)
- Division of Cancer Epidemiology and Genetics (US)
- ORCID
- Venue
- Nutrition and Cancer
- Publisher
- Informa UK Limited
- Published
- 2008-09-05
- Volume
- 60
- Issue
- 5
- Pages
- 652-659
- ISSN
- 0163-5581 (ISSN-L)
- 1532-7914
- PMC
- PMC3490215
- OpenAlex
- W1969078293
- Cited by
- 36
- References
- 36
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 1 · 2014: 6 · 2013: 3 · 2012: 1
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nutrition and Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (Z01DK053211)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Keywords
- SLC23A1, SLC23A2, sodium-dependent vitamin C transporters, SVCT1, SVCT2, vitamin C, colorectal adenoma, advanced colorectal neoplasia, single nucleotide polymorphisms, haplotypes, genetic susceptibility, colorectal cancer risk, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
- MeSH terms
- Adenoma, Aged, Female, Haplotypes, Humans, Male, Middle Aged, Polymorphism, Genetic, Surveys and Questionnaires, Risk Factors, United States, Genetic Variation, Colorectal Neoplasms, Case-Control Studies, Symporters, Organic Anion Transporters, Sodium-Dependent, Sodium-Coupled Vitamin C Transporters
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