Sunday, November 18, 2012

Possible Genetic Predisposition to Lymphedema after Breast Cancer

Possible Genetic Predisposition to Lymphedema after Breast Cancer

Lymphat Res Biol. 2012

Beth Newman, Ph.D.,1 Felicity Lose, Ph.D.,2 Mary-Anne Kedda, Ph.D.,1 Mathias Francois, Ph.D.,3 Kaltin Ferguson,2 Monika Janda, Ph.D.,1 Patsy Yates, Ph.D.,4 Amanda B. Spurdle, Ph.D.,2,* and Sandra C. Hayes, PhDcorresponding author1,*


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.

Methods and 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 SOX18VEGFCVEGFD,VEGFR2, VEGFR3RORCFOXC2, 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 significancstatistical significance  or extreme risk estimates


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.