Prognostic Significance of Vitamin D Receptor Polymorphisms in Head and Neck Squamous Cell Carcinoma
Prognostic Significance of Vitamin D Receptor Polymorphisms in Head and Neck Squamous Cell Carcinoma
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DOI：
10.1371/journal.pone.0029634
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发表时间：
2011-12-29
期刊：
影响因子：
3.7
通讯作者：
Urashima, Mitsuyoshi
中科院分区：
文献类型：
--
作者：
Hama, Takanori;Norizoe, Chihiro;Urashima, Mitsuyoshi
背景：据报道，在晚期非小细胞肺癌患者中，维生素D受体(VDR)基因多态和单倍型与生存相关。方法：在我们先前前瞻性队列研究的后期分析中，对204例接受肿瘤切除的头颈部鳞状细胞癌患者的VDR基因进行了基因分型，包括CDX2 G/A(Rs11568820)、FokI C/T(Rs10735810)、BsmI A/G(Rs1544410)、Apai G/T(Rs7976091)和TaqI T/C(Rs731236)。采用Kaplan-Meier生存曲线和Cox比例风险模型比较VDR基因多态性与COX比例风险模型的无进展生存率。结果：中位随访1047天，76例(37.3%)患者肿瘤进展，27例(13.2%)死亡。FokI T/T基因型与较差的无进展生存率相关：T/T的中位生存期为265天，而C/C或C/T的中位生存期为1,127天(对数等级检验：P=0.0004；调整后的危险比为3.0；95%可信区间为1.62~5.67；P=0.001)。相反，其他多态(CDX2、BsmI、Apai、TaqI)与无进展生存期无显著关联。A-T-G(CDX2-FokI-Apai)单倍型与HNSCC的进展率显著相关(P=0.02)。结论：VDR基因多态性和单倍型可能与HNSCC患者的预后有关，尽管样本量还不够大，不能得出明确的结论。
Background: In patients with advanced non-small-cell lung cancer, vitamin D receptor (VDR) polymorphisms and haplotypes are reported to be associated with survival. We hypothesized that a similar association would be observed in patients with head and neck squamous-cell carcinoma (HNSCC).Methods: In a post-hoc analysis of our previous prospective cohort study, VDR polymorphisms including Cdx2 G/A (rs11568820), FokI C/T (rs10735810), BsmI A/G (rs1544410), ApaI G/T (rs7976091), and TaqI T/C (rs731236) were genotyped by sequencing in 204 consecutive patients with HNSCC who underwent tumor resection. Progression-free survival was compared between VDR polymorphisms using Kaplan-Meier survival curves with log-rank tests and Cox proportional hazard models adjusting for age, gender, smoking status, primary tumor sites, postoperative stages, existence of residual tumor, and postoperative treatment with chemotherapy or radiotherapy.Results: During a median follow-up of 1,047 days, tumor progression and death occurred in 76 (37.3%) and 27 (13.2%) patients, respectively. The FokI T/T genotype was associated with poor progression-free survival: median survival for T/T was 265 days compared with 1,127 days for C/C or C/T (log-rank test: P = 0.0004; adjusted hazard ratio, 3.03; 95% confidence interval, 1.62 to 5.67; P = 0.001). In contrast, the other polymorphisms (Cdx2, BsmI, ApaI, TaqI) showed no significant association with progression-free survival. The A-T-G (Cdx2-FokI-ApaI) haplotype demonstrated a significant association with a higher progression rate (P = 0.02).Conclusion: These results suggest that VDR polymorphisms and haplotypes may be associated with prognosis in patients with HNSCC, although the sample size is not large enough to draw definitive conclusions.