Genetic Variations and Health-Related Quality of Life (HRQOL): A Genome-Wide Study Approach

SIMPLE SUMMARY: Health-related quality of life (HRQOL) is associated with cancer prognosis as well as with age, sex, race, and lifestyle factors, including diet and physical activity. To investigate the hypothesis that HRQOL has genetic underpinnings in patients with cancer, we performed a genome-wide association study to evaluate genetic variants (single nucleotide polymorphisms, SNPs) associated with mental and physical QOL as measured by the PROMIS assessment tool in breast cancer survivors participating in a longitudinal cohort study, the Mayo Clinic Breast Disease Registry (MCBDR). Age and financial concerns were associated with worse physical and mental health, and previous receipt of chemotherapy was associated with worse mental health. SNPs in SCN10A, LMX1B, SGCD, PARP12, and SEMA5A were associated with physical and mental QOL, but none at the genome-wide significance thresholds of p < 5 × 10(−8). ABSTRACT: Health-related quality of life (HRQOL) is an important prognostic patient-reported outcome in oncology. Because prior studies suggest that HRQOL is, in part, heritable, we performed a GWAS to elucidate genetic factors associated with HRQOL in breast cancer survivors. Physical and mental HRQOL were measured via paper surveys that included the PROMIS-10 physical and mental health domain scales in 1442 breast cancer survivors participating in the Mayo Clinic Breast Disease Registry (MCBDR). In multivariable regression analyses, age and financial concerns were significantly associated with global physical health (age: p = 1.6 × 10(−23); financial concerns: p = 4.8 × 10(−40)) and mental health (age: p = 3.5 × 10(−7); financial concerns: p = 2.0 × 10(−69)). Chemotherapy was associated with worse global mental health (p = 0.01). In the GWAS, none of the SNPs reached the genome-wide association significance threshold of 5 × 10(−8) for associations with either global physical or global mental health, however, a cluster of SNPs in SCN10A, particularly rs112718371, appeared to be linked to worse global physical health (p = 5.21 × 10(−8)). Additionally, SNPs in LMX1B, SGCD, PARP12 and SEMA5A were also moderately associated with worse physical and mental health (p < 10(−6)). These biologically plausible candidate SNPs warrant further study as possible predictors of HRQOL.