Association of genetic variants with patient reported quality of life and pain experience in patients in the UK NCRI Myeloma X Relapse [Intensive]) trial; an exploratory study

Abstract

The Myeloma X trial provided a platform to explore genetics in relation to systematic assessment of patient-reported outcomes at key points during salvage treatment in multiple myeloma (MM) patients. Blood DNA was obtained in 191 subjects for single nucleotide polymorphism (SNP) genotyping. By univariable analysis, the non-coding rs2562456 SNP, upstream of LINC00664, was associated with several relevant pain and health-related quality-of-life (HRQoL) scores at 100 days after allocation to consolidation with autologous stem cell transplantation or weekly cyclophosphamide. Presence of the minor (C) allele was associated with lower pain interference (p = 0.014) and HRQoL pain (p = 0.003), and higher HRQoL global health status (p = 0.011) and physical functioning (p = 0.007). These effects were not modified by treatment arm and were no longer significant at 6 months. Following induction therapy, the rs13361160 SNP near the CCT5 and FAM173B genes was associated with higher global health (p = 0.027) and physical functioning (p = 0.013). This exploratory study supports associations between subjective parameters in MM with SNPs previously identified in genome-wide association studies of pain. Conversely, SNPs in candidate genes involved in opioid and transporter pathways showed no effect. Further studies are warranted in well-defined cancer populations, and potentially assisted by whole genome sequencing with germline analysis in routine diagnostics in haematological cancers.

Fig. 1. The SNP rs2562456 is associated with pain and quality of life scores at 100 days post-treatment allocation.

Box and whisker plots by SNP genotype for a BPI pain interference score, b HRQoL pain score, c HRQoL global health status score, and d HRQoL physical functioning score, at 100 days. The X-axes show SNP genotype group and the number of individuals of each genotype in brackets. Regression p values for univariable analyses are as follows. a: 0.014; b: 0.011; c. 0.007; d: 0.003; see Table 3.

Fig. 2. The SNP rs13361160 is associated with HRQoL global Health status and HRQoL physical functioning scores at the end of induction therapy.

Box and whisker plots by SNP genotype for a: HRQoL global health status and b: HRQoL physical functioning post-induction therapy. The X-axes show SNP genotype group and the number of individuals of each genotype in brackets. Regression p values for univariable analyses are as follows. a: 0.027, b: 0.013; see Table 3.