title: Possible genetic predisposition to lymphedema after breast cancer.
abstract: BACKGROUND
  Known risk factors for secondary lymphedema only partially explain who develops lymphedema following cancer, suggesting that inherited genetic susceptibility may influence risk. Moreover, identification of molecular signatures could facilitate lymphedema risk prediction prior to surgery or lead to effective drug therapies for prevention or treatment. Recent advances in the molecular biology underlying development of the lymphatic system and related congenital disorders implicate a number of potential candidate genes to explore in relation to secondary lymphedema.
  
  
  RESULTS
  We undertook a nested case-control study, with participants who had developed lymphedema after surgical intervention within the first 18 months of their breast cancer diagnosis serving as cases (n=22) and those without lymphedema serving as controls (n=98), identified from a prospective, population-based, cohort study in Queensland, Australia. TagSNPs that covered all known genetic variation in the genes SOX18, VEGFC, VEGFD, VEGFR2, VEGFR3, RORC, FOXC2, LYVE1, ADM, and PROX1 were selected for genotyping. Multiple SNPs within three receptor genes, VEGFR2, VEGFR3, and RORC, were associated with lymphedema defined by statistical significance (p<0.05) or extreme risk estimates (OR <0.5 or >2.0).
  
  
  CONCLUSIONS
  These provocative, albeit preliminary, findings regarding possible genetic predisposition to secondary lymphedema following breast cancer treatment warrant further attention for potential replication using larger datasets.
authors.affiliation: Institute of Health and Biomedical Innovation and School of Public Health, Queensland University of Technology, Brisbane, Australia.
authors.forename: Beth
authors.initials: B
authors.lastname: Newman
authors.forename: Felicity
authors.initials: F
authors.lastname: Lose
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Kedda
authors.forename: Mathias
authors.initials: M
authors.lastname: Francois
authors.forename: Kaltin
authors.initials: K
authors.lastname: Ferguson
authors.forename: Monika
authors.initials: M
authors.lastname: Janda
authors.forename: Patsy
authors.initials: P
authors.lastname: Yates
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Hayes
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008208:Lymphatic System; D008209:Lymphedema / Q000453:epidemiology / Q000209:etiology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D011793:Queensland / Q000453:epidemiology; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor