Publication:

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

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.