Abstract
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(trend) < 0.001, MCS P(trend) < 0.001) and education (PCS P(trend) < 0.001, MCS P(trend) < 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(log-rank) < 0.001). These findings suggest that multiple factors contribute to QOL in lung cancer patients, and baseline QOL can impact survival.