Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Medicine, University of California at San Diego Moores Cancer Center, La Jolla, California, USA.
Sci Rep. 2018 Jul 13;8(1):10640. doi: 10.1038/s41598-018-25712-1.
Patient reported health-related quality of life (QOL) is a major component of the overall well-being of cancer patients, with links to prognosis. In 6,420 lung cancer patients, we identified patient characteristics and genetic determinants of QOL. Patient responses from the SF-12 questionnaire was used to calculate normalized Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Further, we analyzed 218 single nucleotide polymorphisms (SNPs) in the p38 MAPK signaling pathway, a key mediator of response to cellular and environmental stress, as genetic determinants of QOL in a subset of the study population (N = 641). Trends among demographic factors for mean PCS and MCS included smoking status (PCS P < 0.001, MCS P < 0.001) and education (PCS P < 0.001, MCS P < 0.001). Similar relationships were seen for MCS. The homozygous rare genotype of MEF2B: rs2040562 showed an increased risk of a poor MCS (OR: 3.06, 95% CI: 1.05-8.92, P = 0.041). Finally, survival analysis showed that a low PCS or a MCS was associated with increased risks of five-year mortality (HR = 1.63, 95% CI: 1.51-1.77, HR = 1.23, 95% CI: 1.16-1.32, respectively) and there was a significant reduction in median survival time (P < 0.001). These findings suggest that multiple factors contribute to QOL in lung cancer patients, and baseline QOL can impact survival.
患者报告的健康相关生活质量(QOL)是癌症患者整体幸福感的主要组成部分,与预后相关。在 6420 例肺癌患者中,我们确定了患者特征和 QOL 的遗传决定因素。使用 SF-12 问卷中的患者应答来计算标准化的身体成分综合评分(PCS)和心理成分综合评分(MCS)。此外,我们分析了 p38 MAPK 信号通路中的 218 个单核苷酸多态性(SNP),该通路是对细胞和环境应激反应的关键介质,作为研究人群亚组中 QOL 的遗传决定因素(N=641)。对于平均 PCS 和 MCS 的人口统计学因素趋势包括吸烟状况(PCS P<0.001,MCS P<0.001)和教育程度(PCS P<0.001,MCS P<0.001)。对于 MCS 也观察到类似的关系。MEF2B 的纯合罕见基因型:rs2040562 显示出 MCS 较差的风险增加(OR:3.06,95%CI:1.05-8.92,P=0.041)。最后,生存分析显示低 PCS 或 MCS 与五年死亡率增加相关(HR=1.63,95%CI:1.51-1.77,HR=1.23,95%CI:1.16-1.32),中位生存时间显著缩短(P<0.001)。这些发现表明,多种因素会影响肺癌患者的 QOL,而基线 QOL 可能会影响生存。