Polymorphisms of peroxisome proliferator-activated receptors and survival of lung cancer and upper aero-digestive tract cancers.
Polymorphisms of peroxisome proliferator-activated receptors and survival of lung cancer and upper aero-digestive tract cancers.
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DOI：
10.1016/j.lungcan.2014.06.014
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Zhang ZF
中科院分区：
文献类型：
--
作者：
Yang Y;Burke RV;Jeon CY;Chang SC;Chang PY;Morgenstern H;Tashkin DP;Mao J;Cozen W;Mack TM;Rao J;Zhang ZF
过氧化物酶体增殖物激活受体（PPARs）是参与多种生物学过程的转录因子，如炎症、癌症生长、进展和凋亡，在肺和上气消化道（UADT）癌症结局中起重要作用。尽管如此，目前还没有关于PPARs基因多态性与肺癌或UADT癌症患者生存之间关系的已发表研究。1212名癌症患者（611名肺癌患者，303名口腔癌患者，100名咽喉癌患者，90名喉癌患者，108名食管癌患者）被随访，平均时间为11年。我们使用Taqman对PPARD基因的rs3734254和PPARG基因的rs10865710和rs1801282三个潜在功能的单核苷酸多态性（snp）进行了基因分型，并使用Cox回归研究了它们与肺癌和UADT癌症生存的关系。在检查多个关联时，使用半贝叶斯收缩方法来减少假阳性结果的可能性。PPARD rs3734254的变异纯合子CC （vs. TT）与肺癌（校正风险比[aHR] = 0.63, 95%可信区间[CI] = 0.42, 0.96）和UADT癌症（aHR = 0.51, 95% CI = 0.27, 0.99）的死亡率呈负相关。使用半贝叶斯收缩法，肺癌的后侧aHR为0.66(95%后限= 0.44,0.98)，UADT癌症的后侧aHR为0.58（95%后限= 0.33,1.03）。我们的研究结果表明，携带PPARD rs3734254 CC变异的肺癌患者可能比携带其他基因变异的肺癌患者具有生存优势。
Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in several biological processes such as inflammation, cancer growth, progression and apoptosis that are important in lung and upper aero-digestive tract (UADT) cancer outcomes. Nonetheless, there are no published studies of the relationship between PPARs gene polymorphisms and survival of patients with lung cancer or UADT cancers. 1,212 cancer patients (611 lung, 303 oral, 100 pharyngeal, 90 laryngeal, and 108 esophageal) were followed for a median duration of 11 years. We genotyped three potentially functional single nucleotide polymorphisms (SNPs) using Taqman--rs3734254 of the gene PPARD and rs10865710 and rs1801282 of the gene PPARG--and investigated their associations with lung and UADT cancer survival using Cox regression. A semi-Bayesian shrinkage approach was used to reduce the potential for false positive findings when examining multiple associations. The variant homozygote CC (vs. TT) of PPARD rs3734254 was inversely associated with mortality of both lung cancer (adjusted hazard ratio [aHR] = 0.63, 95% confidence interval [CI] = 0.42, 0.96) and UADT cancers (aHR = 0.51, 95% CI = 0.27, 0.99). Use of the semi-Bayesian shrinkage approach yielded a posterior aHR for lung cancer of 0.66 (95% posterior limits = 0.44, 0.98) and a posterior aHR for UADT cancers of 0.58 (95% posterior limits = 0.33, 1.03). Our findings suggest that lung-cancer patients with the CC variant of PPARD rs3734254 may have a survival advantage over lung-cancer patients with other gene variants.