Abstract
Introduction Gemcitabine, a cytotoxic drug, is used to treat a variety of solid tumors, such as pancreatic, lung, and breast malignancies. The efficiency rates for gemcitabine have decreased due to an increase in genetic instability. The association between gene polymorphisms and the efficacy of gemcitabine therapy may be better known by understanding the intricacies of genetics that target a few or more genes in drug-targeting metabolic pathways. Moreover, several studies have documented differences in the therapeutic response among various ethnicities to gemcitabine chemotherapy. Therefore, the purpose of this study was to determine the normative frequencies of gene polymorphisms linked to the metabolic pathway of gemcitabine (DCK -360C>G (80143932), SLC29A1 -201A>G (760370), SLC29A1 +913C>T (9394992), SLC29A3 +4967C>A (10999776)) in Southern part of Indian healthy population and compared it with the 1000 genome population. In addition, the association of the above single nucleotide polymorphisms (SNPs) with lung cancer susceptibility was also evaluated. Methods The present study used real-time polymerase chain reaction (RT-PCR) for performing genotyping in 184 healthy participants as well as 123 South Indian patients with lung cancer. The frequencies of alleles and genotypes of the aforementioned genetic variants were in Hardy-Weinberg equilibrium (p > 0.05). Results The minor allele frequencies (MAF) of the SNPs DCK -360C>G (80143932), SLC29A1 -201A>G (760370), SLC29A1+913C>T (9394992), SLC29A3 +4967C>A (10999776) were 3.8%, 17.7%, 27.7%, 29.3% respectively in healthy population. The MAF of the SNPs, DCK -360C>G (80143932), SLC29A1 -201A>G (760370), SLC29A1 +913C>T (9394992), SLC29A3 +4967C>A (10999776) in lung cancer patients was 2%, 15%, 23.2%, and 24.4% respectively. A trend toward a protective effect against lung cancer was observed with SLC29A1 +913C>T (9394992). Conclusion The observed frequencies of alleles and genotypes in the South Indian population were significantly different as compared to the 1000 genome population. In the present study, an association of SLC29A1 rs9394992 C>T between lung cancer patients and healthy subjects showed a trend toward protective effect against lung cancer risk. There was no association found between the other studied SNPs and lung cancer risk.