Precision assessment of heterogeneity of lymphedema phenotype, genotypes and risk prediction

Mei R. Fu, Yvette P. Conley, Deborah Axelrod, Amber A. Guth, Gary Yu, Jason Fletcher, David Zagzag

Research output: Contribution to journalArticle

Abstract

Lymphedema following breast cancer surgery is considered to be mainly due to the mechanical injury from surgery. Recent research identified that inflammation-infection and obesity may be the important predictors for lymphedema. The purpose of this exploratory research was to prospectively examine phenotype of arm lymphedema defined by limb volume and lymphedema symptoms in relation to inflammatory genes in women treated for breast cancer. A prospective, descriptive and repeated-measure design using candidate gene association method was used to enroll 140 women at pre-surgery and followed at 4-8 weeks and 12 months post-surgery. Arm lymphedema was determined by a perometer measurement of ≥5% limb volume increase from baseline of pre-surgery. Lymphedema symptom phenotype was evaluated using a reliable and valid instrument. Saliva samples were collected for DNA extraction. Genes known for inflammation were evaluated, including lymphatic specific growth factors (VEGF-C & VEGF-D), cytokines (IL1-a, IL-4, IL6, IL8, IL10, & IL13), and tumor necrosis factor-a (TNF-a). No significant associations were found between arm lymphedema phenotype and any inflammatory genetic variations. IL1-a rs17561 was marginally associated with symptom count phenotype of ≥8 symptoms. IL-4 rs2070874 was significantly associated with phenotype of impaired limb mobility and fluid accumulation. Phenotype of fluid accumulation was significantly associated with IL6 rs1800795, IL4 rs2243250 and IL4 rs2070874. Phenotype of discomfort was significantly associated with VEGF-C rs3775203 and IL13 rs1800925. Precision assessment of heterogeneity of lymphedema phenotype and understanding the biological mechanism of each phenotype through the exploration of inherited genetic susceptibility is essential for finding a cure. Further exploration of investigative intervention in the context of genotype and gene expressions would advance our understanding of heterogeneity of lymphedema phenotype.

Original languageEnglish (US)
JournalBreast
DOIs
StateAccepted/In press - Mar 14 2016

Fingerprint

Lymphedema
Genotype
Phenotype
Interleukin-4
Vascular Endothelial Growth Factor C
Arm
Interleukin-13
Extremities
Interleukin-6
Vascular Endothelial Growth Factor D
Genes
Inflammation
Genetic Predisposition to Disease
Interleukin-8
Saliva
Research
Interleukin-10
Intercellular Signaling Peptides and Proteins
Tumor Necrosis Factor-alpha
Obesity

Keywords

  • Cancer
  • Genotype
  • Lymphedema
  • Phenotype
  • Risk
  • Symptoms

ASJC Scopus subject areas

  • Surgery

Cite this

Fu, M. R., Conley, Y. P., Axelrod, D., Guth, A. A., Yu, G., Fletcher, J., & Zagzag, D. (Accepted/In press). Precision assessment of heterogeneity of lymphedema phenotype, genotypes and risk prediction. Breast. https://doi.org/10.1016/j.breast.2016.06.023

Precision assessment of heterogeneity of lymphedema phenotype, genotypes and risk prediction. / Fu, Mei R.; Conley, Yvette P.; Axelrod, Deborah; Guth, Amber A.; Yu, Gary; Fletcher, Jason; Zagzag, David.

In: Breast, 14.03.2016.

Research output: Contribution to journalArticle

Fu, Mei R. ; Conley, Yvette P. ; Axelrod, Deborah ; Guth, Amber A. ; Yu, Gary ; Fletcher, Jason ; Zagzag, David. / Precision assessment of heterogeneity of lymphedema phenotype, genotypes and risk prediction. In: Breast. 2016.
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abstract = "Lymphedema following breast cancer surgery is considered to be mainly due to the mechanical injury from surgery. Recent research identified that inflammation-infection and obesity may be the important predictors for lymphedema. The purpose of this exploratory research was to prospectively examine phenotype of arm lymphedema defined by limb volume and lymphedema symptoms in relation to inflammatory genes in women treated for breast cancer. A prospective, descriptive and repeated-measure design using candidate gene association method was used to enroll 140 women at pre-surgery and followed at 4-8 weeks and 12 months post-surgery. Arm lymphedema was determined by a perometer measurement of ≥5{\%} limb volume increase from baseline of pre-surgery. Lymphedema symptom phenotype was evaluated using a reliable and valid instrument. Saliva samples were collected for DNA extraction. Genes known for inflammation were evaluated, including lymphatic specific growth factors (VEGF-C & VEGF-D), cytokines (IL1-a, IL-4, IL6, IL8, IL10, & IL13), and tumor necrosis factor-a (TNF-a). No significant associations were found between arm lymphedema phenotype and any inflammatory genetic variations. IL1-a rs17561 was marginally associated with symptom count phenotype of ≥8 symptoms. IL-4 rs2070874 was significantly associated with phenotype of impaired limb mobility and fluid accumulation. Phenotype of fluid accumulation was significantly associated with IL6 rs1800795, IL4 rs2243250 and IL4 rs2070874. Phenotype of discomfort was significantly associated with VEGF-C rs3775203 and IL13 rs1800925. Precision assessment of heterogeneity of lymphedema phenotype and understanding the biological mechanism of each phenotype through the exploration of inherited genetic susceptibility is essential for finding a cure. Further exploration of investigative intervention in the context of genotype and gene expressions would advance our understanding of heterogeneity of lymphedema phenotype.",
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AB - Lymphedema following breast cancer surgery is considered to be mainly due to the mechanical injury from surgery. Recent research identified that inflammation-infection and obesity may be the important predictors for lymphedema. The purpose of this exploratory research was to prospectively examine phenotype of arm lymphedema defined by limb volume and lymphedema symptoms in relation to inflammatory genes in women treated for breast cancer. A prospective, descriptive and repeated-measure design using candidate gene association method was used to enroll 140 women at pre-surgery and followed at 4-8 weeks and 12 months post-surgery. Arm lymphedema was determined by a perometer measurement of ≥5% limb volume increase from baseline of pre-surgery. Lymphedema symptom phenotype was evaluated using a reliable and valid instrument. Saliva samples were collected for DNA extraction. Genes known for inflammation were evaluated, including lymphatic specific growth factors (VEGF-C & VEGF-D), cytokines (IL1-a, IL-4, IL6, IL8, IL10, & IL13), and tumor necrosis factor-a (TNF-a). No significant associations were found between arm lymphedema phenotype and any inflammatory genetic variations. IL1-a rs17561 was marginally associated with symptom count phenotype of ≥8 symptoms. IL-4 rs2070874 was significantly associated with phenotype of impaired limb mobility and fluid accumulation. Phenotype of fluid accumulation was significantly associated with IL6 rs1800795, IL4 rs2243250 and IL4 rs2070874. Phenotype of discomfort was significantly associated with VEGF-C rs3775203 and IL13 rs1800925. Precision assessment of heterogeneity of lymphedema phenotype and understanding the biological mechanism of each phenotype through the exploration of inherited genetic susceptibility is essential for finding a cure. Further exploration of investigative intervention in the context of genotype and gene expressions would advance our understanding of heterogeneity of lymphedema phenotype.

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