A genetic variant (rs17251221) in the calcium-sensing receptor relates to hepatocellular carcinoma susceptibility and clinical outcome treated by transcatheter hepatic arterial chemoembolization (TACE) therapy.

Experimental and epidemiologic studies indicated that calcium-sensing receptor (CaSR) polymorphisms were associated with cancer risk, yet no data are available for candidate gene and hepatocellular carcinoma (HCC) risk. To address this, we evaluated whether CaSR rs17251221 polymorphism is associated with HCC susceptibility, clinicopathological parameters, and prognosis in HCC patients treated by TACE. A TaqMan assay was used to genotype rs17251221 SNP in this case (n = 843)-control (n = 783) study. A significant increased risk of HCC was observed in patients carrying rs17251221 GG (adjusted OR 1.355, 95 % CI 1.024-1.793, P = 0.033), AG/GG genotype (adjusted OR 1.254, 95 % CI 1.007-1.561, P = 0.043), and G allele (adjusted OR 1.163, 95 % CI 1.013-1.335, P = 0.032). Furthermore, a significant association was found between Child-Pugh class, serum BCLC stage, and AFP level and rs17251221 genotypes. More importantly, individuals carrying rs17251221 AG, GG genotype showed significantly longer MST than AA genotype and significant hazard ration (AG: adjusted HR 0.484, 95 % CI 0.406-0.577, P < 0.001; GG: adjusted HR 0.633, 95 % CI 0.575-0.697, P < 0.001, respectively). Meanwhile, we found a favorable HR for AG/GG genotype carriers (adjusted HR 0.645, 95 % CI 0.542-0.768, P < 0.001). These results indicated that CaSR rs17251221 polymorphism is associated with susceptibility to HCC, and rs17251221 G allele genotype showed significant independent better prognosis of HCC patients treated with TACE.