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.

Conclusion: 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.

Figure 1. Haplotype distribution within GC gene according to Tag-SNPs selected by Haploview v4.2.

Genotyped SNPs are indicated by their rs#. LD Blocks are shown in gray. GC gene chromosomic location and ideogram in reverse orientation appears on the top of the figure, where boxes represent exons and horizontal black lines introns. Bold denotes associated risk alleles, and light grey lines indicate connected haplotypes.