Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer
Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer
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DOI：
10.1093/carcin/bgp076
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发表时间：
2009-06-01
期刊：
影响因子：
4.7
通讯作者：
Kelsey, Karl T.
中科院分区：
文献类型：
--
作者：
Chen, Alyce A.;Marsit, Carmen J.;Kelsey, Karl T.
人乳头瘤病毒（HPV）16型感染是头颈部鳞状细胞癌（HNSCC）的一个病因。目前尚不清楚宿主遗传易感性是否会改变HPV 16-HNSCC的关联。作为波士顿地区HNSCC病例对照研究的一部分收集的DNA样本从国家癌症研究所的SNP 500癌症数据库中进行单核苷酸多态性（SNP）基因分型。采用非条件Logistic回归分析319例HNSCC病例和495例频率匹配对照的人口统计学、表型和基因型数据。所有报告的P值均为双侧。我们确定了钠依赖性维生素C转运蛋白SLC 23 A2的多态性，该多态性改变了与HPV 16感染相关的HNSCC的风险。在SLC 23 A2处具有野生型等位基因的患者中，与HPV 16阳性血清学相关的HNSCC风险为5.0（95%置信区间（CI）= 3.2-7.8）。然而，在纯合变异基因型患者中，HPV 16相关的HNSCC风险降低[比值比（OR）= 2.8; 95%CI = 1.2-6.2]。此外，当我们测试基因型是否改变柑橘暴露、HPV 16和HNSCC之间的相互作用时，我们发现具有野生型SLC 23 A2等位基因、HPV 16阳性血清学和高柑橘摄入量的人患HNSCC的风险显著增加（OR = 7.4; 95%CI = 3.6-15.1）。这些结果表明，SLC 23 A2遗传变异改变了HPV 16相关的HNSCC，同时也突出了柑橘暴露在这种疾病中的重要作用。
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.