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Association of adrenergic receptor gene polymorphisms in gallbladder cancer susceptibility in a North Indian population

  • Original Article - Cancer Research
  • Published:
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Abstract

Purpose

Gallbladder cancer (GBC), the most common gastrointestinal and biliary tract malignancy, often coincides with gallstone disease (GSD). The genetic variants of adrenergic receptor (ADR) have been previously reported to be associated with hypomotility disorder of cardiovascular system and GSD. Since GSD may function as GBC precursor, the present study aimed to investigate the association of common functional genetic variants of ADRA2A C-1291G, ADRβ3 T190C or Trp64Arg, and ADRβ1 C1165G or Arg389Gly with GBC and GSD susceptibility.

Methods

The present study included a total of 400 histologically confirmed GBC, 230 GSD, and 268 healthy controls. The ADRA2A C-1291G, ADRβ3 T190C, and ADRβ1 C1165G polymorphisms were determined by PCR–RFLP. Statistical analysis was performed by using SPSS version 16.

Results

ADRβ3 T190C polymorphism was significantly associated with increased risk of GBC (CT: Pcorr = 0.015, OR 2.87; CC: Pcorr = 0.038, OR 10.33; C allele: Pcorr = 0.014, OR 2.7; CT + CC: Pcorr = 0.017, OR 3.05). These associations existed even after gallstone and gender stratification. Similarly, ADRβ3 T190C polymorphism was also associated with GSD risk, though limited only to female GSD patients. In contrary, ADRA2A C-1291G conferred a marginally increased risk only in GSD patients. ADRβ1 C1165G polymorphism was not associated with GBC and GSD susceptibility when compared to controls.

Conclusion

ADRβ3 T190C polymorphism is significantly associated with GBC and GSD susceptibility. The ADRβ3 T190C may be involved in the pathophysiology of GBC by both gallstone-dependent pathway and by some other independent mechanisms.

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Abbreviations

GBC:

Gallbladder cancer

ADR:

Adrenergic receptors

HC:

Healthy controls

GSD:

Gallstone disease

SNP:

Single-nucleotide polymorphism

SPSS:

Statistical package for social sciences

FDR:

False discovery rate

OR:

Odds ratio

CI:

Confidence interval

HWE:

Hardy–Weinberg equilibrium

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Acknowledgments

The authors thank Department of Biotechnology and Indian Council of Medical Research, Govt of India, for financial support to carry out the present study.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, 226014, UP, India

    Rajani Rai, Kiran L. Sharma & Balraj Mittal

  2. Department of Surgical Oncology, KGMU, Lucknow, India

    Sanjeev Misra

  3. Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India

    Ashok Kumar

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  1. Rajani Rai
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  2. Kiran L. Sharma
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  3. Sanjeev Misra
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  4. Ashok Kumar
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  5. Balraj Mittal
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Correspondence to Balraj Mittal.

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Rai, R., Sharma, K.L., Misra, S. et al. Association of adrenergic receptor gene polymorphisms in gallbladder cancer susceptibility in a North Indian population. J Cancer Res Clin Oncol 140, 725–735 (2014). https://doi.org/10.1007/s00432-014-1621-7

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  • DOI: https://doi.org/10.1007/s00432-014-1621-7

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