Back to Search Start Over

Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression.

Authors :
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
Source :
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2013 May; Vol. 22 (5), pp. 827-34. Date of Electronic Publication: 2013 Mar 05.
Publication Year :
2013

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.<br />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.<br />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).<br />Conclusions: These findings suggest that genetic variation in angiogenesis and lymphangiogenesis contributes to regional nodal metastasis and progression of melanoma.<br />Impact: Additional research attempting to replicate these results is warranted.

Details

Language :
English
ISSN :
1538-7755
Volume :
22
Issue :
5
Database :
MEDLINE
Journal :
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Publication Type :
Academic Journal
Accession number :
23462921
Full Text :
https://doi.org/10.1158/1055-9965.EPI-12-1129