L-asparaginase (L-ASNase) is an enzyme used most effectively in the treatment of acute lymphoblastic leukemia (ALL) for more than 30 years. It catalyzes the hydrolysis of amino acid l-asparagine to aspartic acid and ammonia, which leads to cell death. Clinical trials have been conducted using L-ASNase in combination with other drugs and radiotherapy, which have led to great success in the treatment of ALL. Treatments consist of induction therapy and central nervous system therapy. The achievement of complete remission in patients is associated with a few side-effects of using L-asparaginase, including pancreatitis, coagulation abnormalities and allergic reactions. Sometimes tumor cells may develop resistance to L-ASNase. To overcome these difficulties, the drug is modified by pegylation or immobilization, and also treatment protocols can be modified to increase the efficiency of the drug.

The X-ray repair cross-complementing (XRCC) gene polymorphisms influence esophageal carcinogenesis by altering the DNA repair capacity. The present study was designed to screen five single nucleotide polymorphisms (SNPs) of XRCC genes for their susceptibility to esophageal cancer (EC) risk. There is no previous report on these polymorphisms for EC from India, where EC frequency is high. Methods: The present study included 497 subjects (213 EC patients and 284 healthy controls). The polymorphisms were screened using the PCR-RFLP method and allele and genotype distribution were compared using chi-square test. Association analysis was done by haplotype analysis and linkage disequilibrium (LD) analysis. Gene-gene interactions were identified using multifactor dimensionality reduction (MDR). The risk was calculated using binary logistic regression. Results: For XRCC1 p.Arg399Gln, a decreased risk for EC was associated with the AA genotype [OR (95% CI): 0.53 (0.3-0.95), p=0.03] even after adjusting for various covariates [OR (95% CI): 0.49 (0.26-0.9), p=0.024] and with the recessive model [OR (95% CI): 0.49 (0.27-0.8), p=0.016]. The GA genotype of p.Arg280His was associated with an increased risk for EC [OR (95% CI): 1.7 (1.0-2.82), p= 0.045] after adjustments. The two XRCC1 polymorphisms, p.Arg399Gln and p.Arg194Trp were in slight LD among EC patients (D ̍́= 0.845, r 2 =0.042). XRCC2 and XRCC3 polymorphisms were not associated with EC risk. Conclusion: XRCC1 p.Arg399Gln plays a protective role in the development of the EC. The study is the first report from India, providing baseline data about genetic polymorphisms in DNA repair genes XRCC1, XRCC2 and XRCC3 modulating overall EC risk.

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