Zhou Wei, Heist Rebecca S, Liu Geoffrey, Neuberg Donna S, Asomaning Kofi, Su Li, Wain John C, Lynch Thomas J, Giovannucci Edward, Christiani David C
Departments of Environmental Health, Occupational Health Program, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2239-45. doi: 10.1158/1055-9965.EPI-06-0023.
Our previous analysis suggested that surgery season in the summer time and high vitamin D intake are associated with improved survival in early-stage non-small cell lung cancer (NSCLC) patients. Here, we investigated the associations of vitamin D receptor (VDR) polymorphisms of Cdx-2 G>A, FokI C>T, and BsmI C>T with overall survival (OS) and recurrence-free survival (RFS) in 373 early-stage NSCLC patients. The data were analyzed using log-rank test and Cox proportional hazards models. The median follow-up time was 71 months (range, 0.1-140 months), with 186 deaths and 127 recurrences. There was no association between VDR polymorphisms and survival, overall or among adenocarcinoma patients. Among squamous cell carcinoma (SCC) patients, the G/A+A/A genotype group of the Cdx-2 polymorphism was associated with better OS: the 5-year OS rates were 41% [95% confidence interval (95% CI), 28-53] for the G/G and 55% (95% CI, 39-71) for the G/A+A/A genotypes, respectively (P = 0.04, log-rank test), with the adjusted hazard ratio of 0.56 (95% CI, 0.33-0.95) for G/A+A/A versus G/G. For the joint effects of the three polymorphisms, subjects with two or more "protective" alleles have better OS among SCC patients, with the adjusted hazard ratios of 0.20 (95% CI, 0.09-0.48), 0.40 (95% CI, 0.19-0.87), and 0.43 (95% CI, 0.19-0.97), respectively, for subjects with two, three, and four or more "protective" alleles when compared with subjects with zero or one "protective" allele (P(trend) = 0.71). Similar associations were found in haplotype analysis and for RFS among SCC patients. In conclusion, VDR polymorphisms may be associated with improved survival among SCC patients of early-stage NSCLC.
我们之前的分析表明，夏季手术季节和高维生素D摄入量与早期非小细胞肺癌（NSCLC）患者生存率提高相关。在此，我们调查了373例早期NSCLC患者中Cdx-2 G>A、FokI C>T和BsmI C>T的维生素D受体（VDR）基因多态性与总生存期（OS）和无复发生存期（RFS）的相关性。使用对数秩检验和Cox比例风险模型分析数据。中位随访时间为71个月（范围0.1 - 140个月），有186例死亡和127例复发。VDR基因多态性与总体生存率或腺癌患者生存率之间无关联。在鳞状细胞癌（SCC）患者中，Cdx-2基因多态性的G/A + A/A基因型组与更好的OS相关：G/G基因型的5年OS率为41% [95%置信区间（95%CI），28 - 53]，G/A + A/A基因型为55%（95%CI，39 - 71）（P = 0.04，对数秩检验），G/A + A/A相对于G/G的调整风险比为0.56（95%CI，0.33 - 0.95）。对于三种多态性的联合效应，在SCC患者中，具有两个或更多“保护性”等位基因的受试者具有更好的OS，与具有零个或一个“保护性”等位基因的受试者相比，具有两个、三个以及四个或更多“保护性”等位基因的受试者的调整风险比分别为0.20（95%CI，0.09 - 0.48）、0.40（95%CI，0.19 - 0.87）和0.43（95%CI，0.19 - 0.97）（P趋势 = 0.71）。在单倍型分析以及SCC患者的RFS中也发现了类似的关联。总之，VDR基因多态性可能与早期NSCLC的SCC患者生存率提高相关。
