Faculty Collaboration Database

Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression. Cancer Epidemiol Biomarkers Prev 2013 May;22(5):827-34

Date

03/07/2013

Pubmed ID

23462921

Pubmed Central ID

PMC3708315

DOI

10.1158/1055-9965.EPI-12-1129

Scopus ID

2-s2.0-84877990041 (requires institutional sign-in at Scopus site)   17 Citations

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.

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

Author List

Park JY, Amankwah EK, Anic GM, Lin HY, 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

Author

Ernest Amankwah PhD Director, Associate Professor in the Clinical and Translational Science Institute department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Disease Progression
Female
Genome-Wide Association Study
Genotyping Techniques
Humans
Lymph Nodes
Lymphangiogenesis
Male
Melanoma
Middle Aged
Neovascularization, Pathologic
Polymorphism, Single Nucleotide
Sentinel Lymph Node Biopsy
Skin Neoplasms
Young Adult