Carcinogenesis Advance Access originally published online on April 3, 2009
Carcinogenesis 2009 30(6):977-981; doi:10.1093/carcin/bgp076
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Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer
1 Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115, USA
2 Division of Biological Sciences in Public Health, Harvard School of Public Health, Boston, MA 02115, USA
3 Department of Pathology and Laboratory Medicine
4 Department of Community Health, Center for Environmental Health and Technology, Brown University, Providence, RI 02912, USA
5 Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118, USA
6 Department of Vaccine Basic Research, Merck and Co., West Point, PA 19486, USA
7 Head and Neck Oncology Program, Dana-Farber Cancer Institute, Boston, MA 02115, USA
8 Masonic Cancer Center
9 Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA
* To whom correspondence should be addressed. Tel: +1 401 863 6420; Fax: +1 401 863 9008; Email: karl_kelsey{at}brown.edu
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 SLC23A2, 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.
Abbreviations: CI, confidence interval; HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus; OR, odds ratio; SNP, single-nucleotide polymorphism
Received January 21, 2009; revised March 15, 2009; accepted March 24, 2009.