Heist Rebecca Suk, Zhou Wei, Wang Zhaoxi, Liu Geoffrey, Neuberg Donna, Su Li, Asomaning Kofi, Hollis Bruce W, Lynch Thomas J, Wain John C, Giovannucci Edward, Christiani David C
Massachusetts General Hospital, USA.
J Clin Oncol. 2008 Dec 1;26(34):5596-602. doi: 10.1200/JCO.2008.18.0406. Epub 2008 Oct 20.
We showed previously that in early-stage non-small-cell lung cancer (NSCLC), serum vitamin D levels and VDR polymorphisms were associated with survival. We hypothesized that vitamin D levels and VDR polymorphisms may also affect survival among patients with advanced NSCLC.
We evaluated the relationship between circulating 25-hydroxyvitamin D levels; VDR polymorphisms, including Cdx-2 G>A (rs11568820), FokI C>T (rs10735810), and BsmI C>T (rs144410); and overall survival among patients with advanced NSCLC. Analyses of survival outcomes were performed using the log-rank test and Cox proportional hazards models, adjusting for sex, stage, and performance status.
There were 294 patients and 233 deaths, with median follow-up of 42 months. We found no difference in survival by circulating vitamin D level. The C/C genotype of the FokI polymorphism was associated with improved survival: median survival for C/C was 21.4 months, for C/T was 12.1 months, and for T/T was 15.6 months (log-rank P = .005). There were no significant effects on survival by the Cdx-2 or BsMI polymorphism. However, having increasing numbers of protective alleles was associated with improved survival (adjusted hazard ratio for two or more v zero to one protective alleles, 0.57; 95% CI, 0.41 to 0.79; P = .0008). On haplotype analysis, the G-T-C (Cdx-2-FokI-BsmI) haplotype was associated with worse survival compared with the most common haplotype of G-C-T (adjusted hazard ratio, 1.61; 95% CI, 1.21 to 2.14; P = .001).
There was no main effect of vitamin D level on overall survival in the advanced NSCLC population. The T allele of the VDR FokI>T polymorphism and the G-T-C (Cdx-2-FokI-BsmI) haplotype were associated with worse survival.
我们之前表明，在早期非小细胞肺癌（NSCLC）中，血清维生素D水平和维生素D受体（VDR）基因多态性与生存率相关。我们推测维生素D水平和VDR基因多态性可能也会影响晚期NSCLC患者的生存率。
我们评估了循环25-羟维生素D水平、VDR基因多态性（包括Cdx-2 G>A（rs11568820）、FokI C>T（rs10735810）和BsmI C>T（rs144410））与晚期NSCLC患者总生存率之间的关系。使用对数秩检验和Cox比例风险模型对生存结果进行分析，并对性别、分期和体能状态进行校正。
共有294例患者，233例死亡，中位随访时间为42个月。我们发现循环维生素D水平对生存率没有差异。FokI基因多态性的C/C基因型与生存率提高相关：C/C基因型的中位生存期为21.4个月，C/T基因型为12.1个月，T/T基因型为15.6个月（对数秩检验P = 0.005）。Cdx-2或BsMI基因多态性对生存率没有显著影响。然而，保护性等位基因数量增加与生存率提高相关（两个或更多保护性等位基因相对于零至一个保护性等位基因的校正风险比为0.57；95%可信区间，0.41至0.79；P = 0.0008）。单倍型分析显示，与最常见的G-C-T单倍型相比，G-T-C（Cdx-2-FokI-BsmI）单倍型与较差的生存率相关（校正风险比，1.61；95%可信区间，1.21至2.14；P = 0.001）。
在晚期NSCLC人群中，维生素D水平对总生存率没有主要影响。VDR FokI>T基因多态性的T等位基因和G-T-C（Cdx-2-FokI-BsmI）单倍型与较差的生存率相关。
