Assessment of genetic predisposition to lymphedema.
195 Background: In the United States, 203,000 women are diagnosed annually with breast cancer (BC). Currently, over 2.3 million women in the United States are breast cancer survivors. With the increased incidence and survivorship, more women are living with the long-term treatment effects such as lymphedema (LE). We are nearing completion of stage one of a three-stage research project to examine genetic factors that potentially predispose BC survivors to develop LE. In stage one, we are working to identify novel genetic polymorphisms pointing to genomic regions and genes associated with LE risk. In stage two, we will use exome sequencing to examine both rare and common genetic variants potentially associated with variation in symptom manifestations of LE in breast cancer survivors; to examine phenotypic and genotypic variation in LE emerging following cancer treatment; and to examine associations between LE phenotypes among breast cancer survivors with LE and genomic factors and non-genomic factors. In stage three, we will replicate at the genetic level the associations detected. Methods: Institutional funding was obtained for a GWAS-design feasibility study with 96 breast cancer survivors with and without LE (48/48). Genetic material (from buccal swabs), limb volume (by perometry and circumferences), and self-reported LE-related symptoms were collected in one laboratory appointment. Results: Ninety-five percent of survivors participating in an on-going longitudinal study consented to participate in the genetic pilot (N=96). Buccal swabs provided yield for DNA extraction (concentration average 174.94 ng/ul). An additional 96 specimens have been collected for a second pilot GWAS (N =192). Conclusions: The pilot findings form the basis for a larger multisite proposed study to examine genetic predisposition to secondary LE. The findings of the larger study will lead to the design and timing of subsequent interventions aimed at reducing LE risk and improving overall survivorship quality of life. Findings concerning interactions among best cancer treatments and LE genetic predisposition will have the potential to guide the selection of cancer treatment to minimize complications when survival outcomes are equivalent across competing treatment approaches.