title: Melanoma risk loci as determinants of melanoma recurrence and survival.
abstract: BACKGROUND
  Steadily high melanoma mortality rates urge for the availability of novel biomarkers with a more personalized ability to predict melanoma clinical outcomes. Germline risk variants are promising candidates for this purpose; however, their prognostic potential in melanoma has never been systematically tested.
  
  
  METHODS
  We examined the effect of 108 melanoma susceptibility single nucleotide polymorphisms (SNPs), associated in recent GWAS with melanoma and melanoma-related phenotypes, on recurrence-free survival (RFS) and overall survival (OS), in 891 prospectively accrued melanoma patients. Cox proportional hazards models (Cox PH) were used to test the associations between 108 melanoma risk SNPs and RFS and OS adjusted by age at diagnosis, gender, tumor stage, histological subtype and other primary tumor characteristics.
  
  
  RESULTS
  We identified significant associations for rs7538876 (RCC2) with RFS (HR=1.48, 95% CI=1.20-1.83, p=0.0005) and rs9960018 (DLGAP1) with both RFS and OS (HR=1.43, 95% CI=1.07-1.91, p=0.01, HR=1.52, 95% CI=1.09-2.12, p=0.01, respectively) using multivariable Cox PH models. In addition, we developed a logistic regression model that incorporates rs7538876, rs9960018, primary tumor histological type and stage at diagnosis that has an improved discriminatory ability to classify 3-year recurrence (AUC=82%) compared to histological type and stage alone (AUC=78%).
  
  
  CONCLUSIONS
  We identified associations between melanoma risk variants and melanoma outcomes. The significant associations observed for rs7538876 and rs9960018 suggest a biological implication of these loci in melanoma progression. The observed predictive patterns of associated variants with clinical end-points suggest for the first time the potential for utilization of genetic risk markers in melanoma prognostication.
authors.forename: Justin
authors.initials: J
authors.lastname: Rendleman
authors.forename: Shulian
authors.initials: S
authors.lastname: Shang
authors.forename: Christine
authors.initials: C
authors.lastname: Dominianni
authors.forename: Jerry F
authors.initials: JF
authors.lastname: Shields
authors.forename: Patrick
authors.initials: P
authors.lastname: Scanlon
authors.forename: Christina
authors.initials: C
authors.lastname: Adaniel
authors.forename: Alexis
authors.initials: A
authors.lastname: Desrichard
authors.forename: Michelle
authors.initials: M
authors.lastname: Ma
authors.forename: Richard
authors.initials: R
authors.lastname: Shapiro
authors.forename: Russell
authors.initials: R
authors.lastname: Berman
authors.forename: Anna
authors.initials: A
authors.lastname: Pavlick
authors.forename: David
authors.initials: D
authors.lastname: Polsky
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Shao
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
authors.affiliation: New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA. tomas.kirchhoff@nyumc.org.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kirchhoff
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D040641:Quantitative Trait Loci; D016019:Survival Analysis