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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

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Abstract

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.

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Abbreviations

CaSR :

Calcium-sensing receptor

SNPs:

Single-nucleotide polymorphisms

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

HBsAg:

Hepatitis B surface antigen

AFP:

Alpha fetoprotein

MST:

Median survival time

DFS:

Disease-free survival

OS:

Overall survival

FEM:

Regimen, 5-fluorouracil, epirubicin, and mitomycin-C

TACE:

Transhepatic arterial chemotherapy and embolization

OR:

Odds ratio

CI:

Confidence interval

HR:

Hazard ratio

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Acknowledgments

The authors gratefully acknowledge the efforts and contributions of doctors, nurses and technical staff at the Shengjing Hospital of China Medical University and First Hospital of Dalian Medical University.

Conflict of interest

None of the authors have any financial or other interests that could be construed as a conflict of interest with regard to the submitted manuscript.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, China Medical University, Heping Ward, Shenyang City, 110001, Liaoning Province, People’s Republic of China

    Qiushi Tang & Minjie Wei

  2. Department of General Surgery, Shengjing Hospital of China Medical University, Heping Ward, Shenyang City, 110001, Liaoning Province, People’s Republic of China

    Ying Zhao

  3. Department of General Surgery, First Hospital of Dalian Medical University, Xigang Ward, Dalian City, 116011, Liaoning Province, People’s Republic of China

    Yulin Wang

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  1. Qiushi Tang
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Correspondence to Minjie Wei.

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Tang, Q., Zhao, Y., Wang, Y. et al. 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. Med Oncol 31, 267 (2014). https://doi.org/10.1007/s12032-014-0267-2

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