Ethnic differences in allele, genotype distributions and lung cancer risk of polymorphisms of gemcitabine metabolic pathway genes in south Indian population

Authors

  • Devika Tirumalasetty Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India
  • Deepak Gopal Shewade Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India
  • Biswajit Dubashi Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India
  • Srinivasa Rao Katiboina Department of Pharmacology, Sri Shankaracharya Institute of Medical Sciences, Bhilai, Chattisgarh 490020, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20183463

Keywords:

CDA, Ethnic, Gemcitabine, Lung cancer risk, Polymorphisms, RRM1

Abstract

Background: Gemcitabine is a widely used cytotoxic drug in the treatment of a number of solid tumors, for instance, lung, pancreatic as well as breast cancer. As a consequence of the progressive genomic instability, the efficiency rates have eventually lowered. Genetic approach targeting one or several genes in drug targeting pathways facilitates substantially more valuable details in explaining the association between variants and also the efficacy of gemcitabine therapy. In addition, several researchers have reported ethnic discrepancies in clinical response to gemcitabine. Thus, the present study was aimed to establish the normative frequencies of genes associated with the metabolic pathway of Gemcitabine (RRM1 -37C>A (rs12806698), RRM1 -524T>C (rs11030918), CDA 79A>C (rs2072671) and CDA 435 C>T (rs1048977) in South Indian healthy population and compared with 1000 genome population. Additionally, the association of these SNPs with the risk of developing lung cancer was also evaluated.

Methods: This study was carried out on 184 healthy subjects and 123 lung cancer patients of South Indian origin and genotyping was done using RT-PCR (Real Time Polymerase Chain Reaction). The frequencies of the above polymorphisms were in Hardy-Weinberg equilibrium (p >0 .05).

Results: The minor allele frequencies of the SNPs RRM1 -37C>A (rs12806698), RRM1 -524T>C (rs11030918), CDA 79A>C (rs2072671) and CDA -435 C>T (rs1048977) were 31.3, 36.7, 24.5 and 22.0 respectively.

Conclusions: There was a significant difference observed between the genotype and allele frequencies of south Indians with the 1000 genome populations. We also found that SNPs of RRM1 were significantly associated with lung cancer risk.

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Published

2018-08-23

How to Cite

Tirumalasetty, D., Shewade, D. G., Dubashi, B., & Katiboina, S. R. (2018). Ethnic differences in allele, genotype distributions and lung cancer risk of polymorphisms of gemcitabine metabolic pathway genes in south Indian population. International Journal of Basic & Clinical Pharmacology, 7(9), 1693–1700. https://doi.org/10.18203/2319-2003.ijbcp20183463

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Original Research Articles