Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer.
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.
Brigham and Women's Hospital, Boston, MA 02115, USA.
Alyce A
AA
Chen
Carmen J
CJ
Marsit
Brock C
BC
Christensen
E Andrés
EA
Houseman
Michael D
MD
McClean
Judith F
JF
Smith
Janine T
JT
Bryan
Marshall R
MR
Posner
Heather H
HH
Nelson
Karl T
KT
Kelsey
D000368:Aged; D016022:Case-Control Studies; D002957:Citrus; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000821:virology; D052162:Human papillomavirus 16; D006801:Humans; D008297:Male; D008875:Middle Aged; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics* / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000235:genetics*
D029363:Organic Anion Transporters, Sodium-Dependent; C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters