Abstract 5045: Genetic and social determinants of quality of life in lung cancer patients

Abstract

Abstract Patient reported health-related quality of life (QOL) has been recognized as a major component of the overall well-being of cancer patients, with links to prognosis and other endpoints. We aimed to identify determinants of baseline QOL by investigating the relationship between patient characteristics, genetic factors, and baseline QOL in lung cancer patients. We included 7,135 newly diagnosed and previously untreated lung cancer patients. Patient reported data from the SF-12 questionnaire was used to calculate baseline Physical Component Summary (PCS) and Mental Component Summary (MCS), with lower scores indicating a worse quality of life. We observed that the mean PCS (38.82) and MCS (46.22) scores were reduced in the lung cancer population when compared to the general population which was normalized to 50. We observed a significant trend for decreasing mean PCS and MCS from never, former, to current smokers (PCS Ptrend<0.0001; MCS Ptrend<0.0001) and a similar significant increasing trend of mean PCS/MCS was seen for education from no high school through college (PCS Ptrend<0.0001; MCS Ptrend<0.0001). When compared to never smokers, current smokers were at an increased risk of reporting a poor PCS (OR: 1.51, 95%CI: 1.18-1.94, P=1.0x10-3). Compared to individuals with less than a high school degree, those with a high school (OR: 0.76, 95%CI: 0.61-0.94, P=1.0x10-2) or college degree (OR: 0.48, 95%CI: 0.38-0.62, P<0.001) had a decreased risk of a poor PCS. A similar relationship was seen for MCS. As cancer stage increased the mean PCS and MCS score decreased (PCS Ptrend<0.0001; MCS Ptrend<0.0001). 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=588). Using the median PCS/MCS score as the cut-off, twenty SNPs were statistically significantly associated with PCS and 26 SNPs were associated with MCS (P<0.05). In the PCS analysis, there was a 3.47-fold (95%CI, 1.75-6.88, P=3.5x10-4) increased risk of reporting a low PCS score in individuals with at least one variant of MAP2K6: rs12600726. At least one variant allele of rs7207011 in MAP2K4 was associated with a lower score for both PCS and MCS (PCS: OR=0.10, 95%CI, 0.01-0.87, P=3.7x10-2; MCS: OR=0.09, 95%CI, 0.01-0.80, P=3.0x10-2). A gene-based analysis identified MEF2D and MAP3K5 as a significant contributor to PCS, but not MCS. Furthermore, MAP2K6 was identified as a significant contributor to both PCS and MCS. Validation for these results is underway. Taken together these findings suggest that multiple factors can contribute to QOL in lung cancer patients. Citation Format: Jeanne A. Pierzynski, Michelle Hildebrandt, Yuanqing Ye, Alma Rodriguez, Xifeng Wu. Genetic and social determinants of quality of life in lung cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5045. doi:10.1158/1538-7445.AM2014-5045