title: rs12512631 on the group specific complement (vitamin D-binding protein GC) implicated in melanoma susceptibility.
abstract: BACKGROUND
  Solar radiation should be avoided in melanoma patients. Nevertheless, this is the main means by which the body produces vitamin D. Evidence suggests a protective role against cancer for vitamin D. Since vitamin D performs its function by binding the receptor encoded by the vitamin D-receptor gene (VDR), most studies have focused on polymorphisms (SNPs) within this gene. However, the gene encoding the vitamin D-binding protein (GC) appears in recent studies as a major player in the role of a serum vitamin D level regulator and in Cutaneous Melanoma (CM) predisposition.
  
  
  METHODS
  We performed a case-control study of 12 polymorphisms on GC and 9 on VDR among 530 cases and 314 controls from Spanish population.
  
  
  RESULTS
  We found association between SNP rs12512631, located 3'downstream of GC, and risk of CM that seems to fit a dominant model (OR 1.63 95%CI 1.23-2.17 p-value 7×10(-4)). This association remained Bonferroni's correction and after adjustment for potential confounders (p-value 3×10(-3)) and even after increasing the sample size to 1729 individuals (p-value 0.0129). Moreover, we confirmed evidence of an association between CM susceptibility and the linkage disequilibrium block marked by tag-SNP rs222016 (p-value 0.032). This block covers the GC intron 1 region, with probable regulatory functions.
  
  
  CONCLUSIONS
  To our knowledge, this is the first vitamin D pathway-related polymorphism study in melanoma risk conducted in the Spanish population. Furthermore, we show an association between polymorphisms in GC and melanoma risk, confirming recent studies in different populations.
authors.affiliation: Medical Oncology and Haematology Unit, Health Research Institute INCLIVA, Valencia, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Peña-Chilet
authors.forename: Maider
authors.initials: M
authors.lastname: Ibarrola-Villava
authors.forename: Manuel
authors.initials: M
authors.lastname: Martin-González
authors.forename: Marta
authors.initials: M
authors.lastname: Feito
authors.forename: Cristina
authors.initials: C
authors.lastname: Gomez-Fernandez
authors.forename: Dolores
authors.initials: D
authors.lastname: Planelles
authors.forename: Gregorio
authors.initials: G
authors.lastname: Carretero
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Eduardo
authors.initials: E
authors.lastname: Nagore
authors.forename: Gloria
authors.initials: G
authors.lastname: Ribas
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics*; D013030:Spain; D014809:Vitamin D-Binding Protein / Q000235:genetics*
chemical_list: D014809:Vitamin D-Binding Protein
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