title: Are race-specific ERCC1 haplotypes in melanoma cases versus controls related to the predictive and prognostic value of ERCC1 N118N?
abstract: OBJECTIVE
  Although it does not alter the ERCC1 phenotype, the ERCC1 500C>T (rs11615) polymorphism has undergone a myriad of investigations into its role as a marker for nucleotide excision repair (NER) function in different races, diseases and treatment outcomes. The goal of our study was to test the hypothesis that 500C>T is in linkage disequilibrium (LD) with causative alleles, and that these haplotypes are more frequent in Caucasians with melanoma than in healthy Caucasians or African Americans.
  
  
  METHODS
  In this case-control study, we selected race-specific ERCC1 single-nucleotide polymorphism (SNPs), conducted LD analysis with ERCC1 500C>T and compared the frequency of ERCC1 diplotypes in Caucasians with melanoma (n=165), healthy Caucasians (n=150) and healthy African Americans (n=159). The haplotype was further studied using a fusion gene containing multiple ERCC1 SNPs.
  
  
  METHODS
  Large cancer institute in the USA.
  
  
  METHODS
  A total of 165 Caucasian melanoma patients, 159 healthy Caucasian controls and 159 African American healthy controls. Men and women were enrolled in the clinical trial; however, since the screening trial included prostate cancer screening in addition to screening for other cancers, only male controls were available.
  
  
  METHODS
  The outcome measures were melanoma risk in Caucasians, and LD between ERCC1 SNP, N118N and other race-specific allelic variants.
  
  
  RESULTS
  When compared to ERCC1 500C>T alone, a race-specific three-SNP variant haplotype in ERCC1 (comprised of rs11615, rs3212950 and rs3212948) was even more frequent in Caucasians with melanoma than in healthy Caucasians (p=0.0034) or African Americans (p<0.0001). A plasmid containing the variant haplotype was not differentially expressed.
  
  
  CONCLUSIONS
  We demonstrate that ERCC1 500C>T participates in a previously characterised cancer-risk haplotype found more frequently in Caucasians, while LD is weak in African Americans; this haplotype appears to also be related to melanoma. It is therefore likely that ERCC1 500C>T is only a valid NER, disease or treatment outcome marker in Caucasians.
authors.affiliation: Molecular Pharmacology Section, Medical Oncology Branch, Center for Cancer Research, Bethesda, Maryland, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Gao
authors.forename: Kelie M
authors.initials: KM
authors.lastname: Reece
authors.forename: Tristan
authors.initials: T
authors.lastname: Sissung
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Fu
authors.forename: David J
authors.initials: DJ
authors.lastname: Venzon
authors.forename: Eddie
authors.initials: E
authors.lastname: Reed
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Spencer
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Price
authors.forename: William D
authors.initials: WD
authors.lastname: Figg