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Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression.

Publication ,  Journal Article
Park, JY; Amankwah, EK; Anic, GM; Lin, H-Y; Walls, B; Park, H; Krebs, K; Madden, M; Maddox, K; Marzban, S; Fang, S; Chen, W; Lee, JE; Wei, Q ...
Published in: Cancer Epidemiol Biomarkers Prev
May 2013

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. IMPACT: Additional research attempting to replicate these results is warranted.

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Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

May 2013

Volume

22

Issue

5

Start / End Page

827 / 834

Location

United States

Related Subject Headings

  • Young Adult
  • Skin Neoplasms
  • Sentinel Lymph Node Biopsy
  • Polymorphism, Single Nucleotide
  • Neovascularization, Pathologic
  • Middle Aged
  • Melanoma
  • Male
  • Lymphangiogenesis
  • Lymph Nodes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Park, J. Y., Amankwah, E. K., Anic, G. M., Lin, H.-Y., Walls, B., Park, H., … Egan, K. M. (2013). Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression. Cancer Epidemiol Biomarkers Prev, 22(5), 827–834. https://doi.org/10.1158/1055-9965.EPI-12-1129
Park, Jong Y., Ernest K. Amankwah, Gabriella M. Anic, Hui-Yi Lin, Brooke Walls, Hyun Park, Kevin Krebs, et al. “Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression.Cancer Epidemiol Biomarkers Prev 22, no. 5 (May 2013): 827–34. https://doi.org/10.1158/1055-9965.EPI-12-1129.
Park JY, Amankwah EK, Anic GM, Lin H-Y, Walls B, Park H, et al. Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression. Cancer Epidemiol Biomarkers Prev. 2013 May;22(5):827–34.
Park, Jong Y., et al. “Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression.Cancer Epidemiol Biomarkers Prev, vol. 22, no. 5, May 2013, pp. 827–34. Pubmed, doi:10.1158/1055-9965.EPI-12-1129.
Park JY, Amankwah EK, Anic GM, Lin H-Y, Walls B, Park H, Krebs K, Madden M, Maddox K, Marzban S, Fang S, Chen W, Lee JE, Wei Q, Amos CI, Messina JL, Sondak VK, Sellers TA, Egan KM. Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression. Cancer Epidemiol Biomarkers Prev. 2013 May;22(5):827–834.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

May 2013

Volume

22

Issue

5

Start / End Page

827 / 834

Location

United States

Related Subject Headings

  • Young Adult
  • Skin Neoplasms
  • Sentinel Lymph Node Biopsy
  • Polymorphism, Single Nucleotide
  • Neovascularization, Pathologic
  • Middle Aged
  • Melanoma
  • Male
  • Lymphangiogenesis
  • Lymph Nodes