Yin Jieyun, Liu Hongliang, Yi Xiaohua, Wu Wenting, Amos Christopher I, Fang Shenying, Lee Jeffrey E, Han Jiali, Wei Qingyi
Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China.
Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
Pigment Cell Melanoma Res. 2016 Mar;29(2):176-85. doi: 10.1111/pcmr.12437. Epub 2016 Jan 29.
Single nucleotide polymorphisms (SNPs) in the vitamin D pathway genes have been implicated in cutaneous melanoma (CM) risk, but their role in CM disease-specific survival (DSS) remains obscure. We comprehensively analyzed the prognostic roles of 2669 common SNPs in the vitamin D pathway genes using data from a published genome-wide association study (GWAS) at The University of Texas M.D. Anderson Cancer Center (MDACC) and then validated the SNPs of interest in another GWAS from the Nurses' Health Study and Health Professionals Follow-up Study. Among the 2669 SNPs, 203 were significantly associated with DSS in MDACC dataset (P < 0.05 and false-positive report probability < 0.2), of which 18 were the tag SNPs. In the replication, two of these 18 SNPs showed nominal significance: the VDBP rs12512631 T > C was associated with a better DSS [combined hazards ratio (HR) = 0.66]; and the same for RXRA rs7850212 C > A (combined HR = 0.38), which were further confirmed by the Fine and Gray competing-risks regression model. Further bioinformatics analyses indicated that these loci may modulate corresponding gene methylation status.
维生素D通路基因中的单核苷酸多态性（SNPs）与皮肤黑色素瘤（CM）风险有关，但其在CM疾病特异性生存（DSS）中的作用仍不清楚。我们利用德克萨斯大学MD安德森癌症中心（MDACC）已发表的全基因组关联研究（GWAS）数据，全面分析了维生素D通路基因中2669个常见SNP的预后作用，然后在护士健康研究和卫生专业人员随访研究的另一项GWAS中验证了感兴趣的SNP。在这2669个SNP中，203个在MDACC数据集中与DSS显著相关（P < 0.05且假阳性报告概率 < 0.2），其中18个是标签SNP。在重复验证中，这18个SNP中有两个显示出名义上的显著性：维生素D结合蛋白（VDBP）rs12512631 T > C与更好的DSS相关[合并风险比（HR） = 0.66]；维甲酸受体α（RXRA）rs7850212 C > A也是如此（合并HR = 0.38），这通过Fine和Gray竞争风险回归模型得到进一步证实。进一步的生物信息学分析表明，这些位点可能调节相应基因的甲基化状态。
