Possible genetic predisposition to lymphedema after breast cancer

Newman, Beth, Lose, Felicity, Kedda, Mary-Anne, Francois, Mathias, Ferguson, Kaltin, Janda, Monika, Yates, Patsy, Spurdle, Amanda B. and Hayes, Sandra C. (2012) Possible genetic predisposition to lymphedema after breast cancer. Lymphatic Research and Biology, 10 1: 2-13. doi:10.1089/lrb.2011.0024


Author Newman, Beth
Lose, Felicity
Kedda, Mary-Anne
Francois, Mathias
Ferguson, Kaltin
Janda, Monika
Yates, Patsy
Spurdle, Amanda B.
Hayes, Sandra C.
Title Possible genetic predisposition to lymphedema after breast cancer
Journal name Lymphatic Research and Biology   Check publisher's open access policy
ISSN 1539-6851
1557-8585
Publication date 2012-03
Sub-type Article (original research)
DOI 10.1089/lrb.2011.0024
Volume 10
Issue 1
Start page 2
End page 13
Total pages 12
Place of publication New Rochelle, NY, United States
Publisher Mary Ann Liebert
Collection year 2013
Language eng
Formatted 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.

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 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.
Keyword Upper-Body Function
Hereditary Lymphedema
Secondary Lymphedema
Orphan Receptor
Ror-Gamma
Lymphatic Vasculature
Molecular-Mechanisms
Transcription Factor
Missense Mutations
Tyrosine Kinase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Online Ahead of Print: 9 March 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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