Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer

Alyce A. Chen, Carmen J. Marsit, Brock C. Christensen, E. Andrés Houseman, Michael D. Mcclean, Judith F. Smith, Janine T. Bryan, Marshall R. Posner, Heather H. Nelson, Karl T. Kelsey

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Human papillomavirus (HPV) type 16 infection is an etiologic factor in a subset of head and neck squamous cell carcinomas (HNSCC). It is unknown if host genetic susceptibility modifies the HPV16-HNSCC association. DNA samples collected as part of a Boston area case-control study of HNSCC were genotyped for single-nucleotide polymorphisms (SNPs) from the National Cancer Institute's SNP500Cancer database. Analysis of demographic, phenotypic and genotypic data for 319 HNSCC cases and 495 frequency-matched controls was performed using unconditional logistic regression. All reported P-values are two sided. We identified a polymorphism in the sodium-dependent vitamin C transporter SLC23A2 that modifies the risk of HNSCC associated with HPV16 infection. Among those with a wild-type allele at SLC23A 2, the risk of HNSCC associated with HPV16-positive serology was 5.0 (95% confidence interval (CI) = 3.2-7.8). However, among those with a homozygous variant genotype, the risk of HNSCC associated with HPV16 was attenuated [odds ratio (OR) = 2.8; 95% CI = 1.2-6.2]. Further, when we tested whether genotype modified the interaction between citrus exposure, HPV16, and HNSCC, we found a dramatically increased risk of HNSCC for those with a wild-type SLC23A2 allele, HPV16-positive serology and high citrus intake (OR = 7.4; 95% CI = 3.6-15.1). These results suggest that SLC23A2 genetic variation alters HPV16-associated HNSCC while also highlighting the important role of citrus exposure in this disease.

Original languageEnglish (US)
Pages (from-to)977-981
Number of pages5
JournalCarcinogenesis
Volume30
Issue number6
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
National Institutes of Health (CA100679, CA78609, T32 ES07155 and T32 CA 09001); Friends of Dana-Farber Cancer Institute; Dan and Gloria Schusterman Foundation.

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