title: Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression.
abstract: BACKGROUND
  Angiogenesis and lymphangiogenesis are important in the progression of melanoma. We investigated associations between genetic variants in these pathways with sentinel lymph node (SLN) metastasis and mortality in 2 independent series of patients with melanoma.
  
  
  METHODS
  Participants at Moffitt Cancer Center were 552 patients, all Caucasian, with primary cutaneous melanoma referred for SLN biopsy. A total of 177 patients had SLN metastasis, among whom 60 died from melanoma. Associations between 238 single-nucleotide polymorphisms (SNP) in 26 genes and SLN metastasis were estimated as ORs and 95% confidence intervals (CI) using logistic regression. Competing risk regression was used to estimate HRs and 95% CI for each SNP and melanoma-specific mortality. We attempted to replicate significant findings using data from a genome-wide association study comprising 1,115 patients with melanoma who were referred for SLN biopsy from MD Anderson Cancer Center (MDACC), among whom 189 patients had SLN metastasis and 92 patients died from melanoma.
  
  
  RESULTS
  In the Moffitt dataset, we observed significant associations in 18 SNPs with SLN metastasis and 17 SNPs with mortality. Multiple SNPs in COL18A1, EGF receptor (EGFR), FLT1, interleukin (IL)-10, platelet-derived growth factor D (PDGFD), PIK3CA, and toll-like receptor (TLR)-3 were associated with the risk of SLN metastasis and/or patient mortality. The MDACC data set replicated an association between mortality and rs2220377 in PDGFD. Furthermore, in a meta-analysis, 3 additional SNPs were significantly associated with SLN metastasis (EGFR rs723526 and TLR3 rs3775292) and melanoma-specific death (TLR3 rs7668666).
  
  
  CONCLUSIONS
  These findings suggest that genetic variation in angiogenesis and lymphangiogenesis contributes to regional nodal metastasis and progression of melanoma.
  
  
  CONCLUSIONS
  Additional research attempting to replicate these results is warranted.
authors: Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA. jong.park@moffitt.org
authors: Jong Y
authors: JY
authors: Park
authors: Ernest K
authors: EK
authors: Amankwah
authors: Gabriella M
authors: GM
authors: Anic
authors: Hui-Yi
authors: HY
authors: Lin
authors: Brooke
authors: B
authors: Walls
authors: Hyun
authors: H
authors: Park
authors: Kevin
authors: K
authors: Krebs
authors: Melissa
authors: M
authors: Madden
authors: Kristen
authors: K
authors: Maddox
authors: Suroosh
authors: S
authors: Marzban
authors: Shenying
authors: S
authors: Fang
authors: Wei
authors: W
authors: Chen
authors: Jeffrey E
authors: JE
authors: Lee
authors: Qingyi
authors: Q
authors: Wei
authors: Christopher I
authors: CI
authors: Amos
authors: Jane L
authors: JL
authors: Messina
authors: Vernon K
authors: VK
authors: Sondak
authors: Thomas A
authors: TA
authors: Sellers
authors: Kathleen M
authors: KM
authors: Egan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D042583:Lymphangiogenesis; D008297:Male; D008545:Melanoma / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult