Objective：Vitamin D and its receptor（VDR） involve in multiple cellular processes and play an important role in the initiation and progression of malignancy.Thus we hypothesized that plasma vitamin D levels and single nucleotide polymorphisms（SNPs） in VDR may be of prognostic significance in non-small cell lung cancer（NSCLC）.Methods：We examined plasma 25-hydroxyvitamin D [25（OH）D] levels in 87 patients diagnosed with NSCLC using enzyme-linked immunosorbent assay（ELISA） and genotyped seven potentially functional SNPs in VDR in 568 NSCLC patients on Illumina Golden Gate platform.Results：Patients with higher plasma 25（OH）D levels had worse survival than patients with lower ones（P for trend = 0.048）.The SNPs of rs1544410 and rs739837 were independently associated with NSCLC survival（adjusted HR = 1.61,95% CIs = 1.06-2.45 for rs739837 AA vs AC/CC and adjusted HR = 1.51,95% CIs = 1.06-2.16 for rs1544410 AG/AA vs GG）.A joint effect was observed between rs1544410 and rs739837 and the risk of death elevated as the number of unfavourable genotypes patients carried increased（P for trend = 0.003）.There were no significant associations between VDR polymorphisms and plasma 25（OH）D levels.Conclusion：Our findings indicate that plasma 25（OH）D levels and genetic variants of VDR may serve as prognostic markers for NSCLC in this Chinese population.
Apoptosis plays a key role in inhibiting tumor growth, progression and resistance to anti-tumor therapy. We hypothesized that genetic variants in apoptotic genes may affect the prognosis of lung cancer. To test this hypoth- esis, we selected 38 potentially functional single nucleotide polymorphisms （SNPs） from 12 genes （BAX, BCL2, BID, CASP3, CASP6, CASP7, CASPS, CASP9, CASPIO, FAS, FASLG and MCL1） involved in apoptosis to assess their prognostic significance in lung cancer in a Chinese case cohort with 568 non-small cell lung cancer （NSCLC） patients. Thirty-five SNPs passing quality control underwent association analyses, 11 of which were shown to be significantly associated with NSCLC survival （P 〈 0.05）. After Cox stepwise regression analyses, 3 SNPs were independently associated with the outcome of NSCLC （BID rs8190315： P = 0.003; CASP9 rs4645981： P = 0.007 and FAS rs1800682： P = 0.016）. A favorable survival of NSCLC was significantly associated with the genotypes of BID rs8190315 AG/GG （adjusted HR = 0.65, 95% CI： 0.49-0.88）, CASP9 rs4645981 AA （HR = 0.22, 95% CI： 0.07-0.69） and FAS rs1800682 GG （adjusted HR = 0.67, 95% CI： 0.46-0.97）. Time-dependent receptor operation curve （ROC） analysis revealed that the area under curve （AUC） at year 5 was significantly increased from 0.762 to 0.819 after adding the risk score of these 3 SNPs to the clinical risk score. The remaining 32 SNPs were not sig- nificantly associated with NSCLC prognosis after adjustment for these 3 SNPs. These findings indicate that BID rs8190315, CASP9 rs4645981 and FAS rs1800682 polymorphisms in the apoptotic pathway may be involved in the prognosis of NSCLC in the Chinese population.
