Single Nucleotide Polymorphisms in the Gc Gene for Vitamin D Binding Protein in Common Cancers in Thailand


Background: This case-control study aimed to determine if there were any associations between the two singlenucleotide polymorphisms (SNPs) in Gc, rs7041 (Asp416Glu) and rs4588 (Thr420Lys) and 3 common cancers(breast, lung and colorectal) in Thai patients. Materials and
Methods: Two hundred and eighty two colorectal,101 breast and 113 lung cancer patients were recruited from one institute during 2011-2013. The controls wereage-matched volunteers who had a negative history of index cancers. In addition, vitamin D levels were comparedamong different genotypes in the 2 SNPs.
Results: The minor allele frequencies of rs7041 (G) and rs4588 (A)were 0.32 and 0.24, respectively. Under the dominant model, the study found significant associations betweenminor-allele genotypes of the SNP rs7041 (TG/GG) and lung cancer (odds ratio [OR] 1.78, 95% CI 1.05-3.03).When subgroup analysis was performed according to sex and age at diagnosis, the study found that the minorallelegenotypes of rs7041 (TG/GG) were significantly associated with colorectal cancer in patients whose age atdiagnosis was more than 60 years (OR 1.67, 95%CI 1.06-2.61) and the minor-allele genotypes of rs4588 (CA/AA)were significantly associated with colorectal cancer in males aged 60 years or less (OR 2.34, 95%CI 1.25-4.37).When SNP combinations (rs7041-rs4588) were examined, the TT-CA combination had a significant protectiveassociation with lung cancer (OR 0.44, 95% CI 0.22-0.85). On evaluation of serum 25(OH)D levels in 205individuals without cancer (males 144, females 61), the proportion of subjects with low serum vitamin D (< 20ng/ml) in those harboring CA or AA genotypes of rs4588 (41.7%) was significantly higher than the CC genotype(15.5%, p-value < 0.01).
Conclusions: Genetic polymorphisms in Gc were associated with lung and colorectalcancers in Thai patients. Lower serum 25(OH)D in minor variants of rs4588 may explain this association.