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Association of DNA repair gene XPC Ala499Val (rs2228000 C>T) and Lys939Gln (rs2228001 A>C) polymorphisms with the risk of chronic myeloid leukemia: A case–control study in a South Indian population
Author(s) -
Lakkireddy Samyuktha,
Aula Sangeetha,
Kapley Atya,
Gundeti Sadashivudu,
Kutala Vijay Kumar,
Jamil Kaiser
Publication year - 2021
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3339
Subject(s) - xeroderma pigmentosum , odds ratio , myeloid leukemia , haplotype , genotype , dna repair , biology , nucleotide excision repair , medicine , single nucleotide polymorphism , genetics , immunology , oncology , cancer research , gene
Background Xeroderma pigmentosum complementation group C (XPC), a DNA repair protein, plays an important role in the maintenance of genomic integrity and is essential for the nucleotide excision repair pathway. Polymorphisms in the XPC gene may alter DNA repair leading to genetic instability and oncogenesis. The present study aimed to assess the relationship between the XPC Ala499Val (rs2228000 C>T) and Lys939Gln (rs2228001 A>C) non‐synonymous polymorphisms and susceptibility to chronic myeloid leukemia (CML) pathogenesis, disease progression and the response to targeted therapeutic regimen, imatinib mesylate. Methods This case–control study included 212 cases and 212 controls, and the genotypes were determined by polymerase chain reaction‐restriction fragment length polymorphism assays. Results Our results showed significant association of variant CT (odds ratio = 1.92, 95% confidence interval = 1.21–3.06, p = 0.003) and TT (odds ratio = 2.84, 95% confidence interval = 1.22–6.71, p = 0.007) genotypes in patients with the XPC Ala499Val polymorphism and CML risk. In addition, these genotypes were associated with CML progression to advanced phases ( p = 0.006), splenomegaly ( p = 0.017) and abnormal lactate dehydrogenase levels ( p = 0.03). XPC Lys939Gln was found to correlate with a poor response to therapy, showing borderline significant association with minor cytogenetic response ( p = 0.08) and a poor molecular response ( p = 0.06). Significant association of the Ala499Val and Lys939Gln polymorphisms with prognosis was observed (Hasford high risk, p = 0.031 and p = 0.019, respectively). Haplotype analysis showed a strong correlation of variant TC haplotype with poor therapy responses (minor cytogenetic response, p = 0.019; poor molecular response, p < 0.0001). Conclusions In conclusion, our results suggest that XPC Ala499Val is a high‐penetrance CML susceptibility polymorphism. Both polymorphisms studied are considered as genetic markers with respect to assessing disease progression, therapy response and prognosis in CML patients.