Polymorphism T81C in H-RAS Oncogene Is Associated With Disease Progression in Imatinib (TKI) Treated Chronic Myeloid Leukemia Patients

Rashid Mir, Imtiyaz Ah, Jamsheed Javid, Mariyam Zuberi, Sameer Guru, Masroor Mirza, Shazia Farooq, Prasant Yadav, Prakash C. Ray, Naresh Gupta, Alpana Saxena


Background: Mammalian cells contain three functional RAS proto-oncogenes, known as H-RAS, K-RAS, and N-RAS, which encode small GTP-binding proteins in terms of p21rass. RAS genes have been elucidated as major participants in the development and progression of cancer. A single nucleotide polymorphism (SNP) at H-RAS cDNA position 81 T→C (rs12628) has been found to be associated with the risk of many human cancers like gastrointestinal, oral, colon, bladder and thyroid carcinomas. Therefore, we hypothesized that this polymorphisms in H-RAS could influence susceptibility to chronic myeloid leukemia as well, and we conducted this study to test the hypothesis in Indian population.

Method: H-RAS polymorphism was studied in 100 chronic myeloid leukemia (CML) patients and 100 healthy controls by restriction fragmentation length polymorphism (RFLP-PCR). Associations between polymorphism and clinicopathological features of CML patients were investigated.

Results: In CML patients, the TT, TC and CC genotype frequency was 38%, 61% and 1% respectively, compared to 92%, 8% and 0% in healthy controls respectively. Compared to TT genotype, CT was significantly associated with increased risk of CML (odds ratio (OR): 8.4, P < 0.00001). There was a statistically significant correlation of H-RAS polymorphism with phases (P < 0.0003), molecular response (P < 0.0001), hematological response (P < 0.04) and thrombocytopenia (P < 0.003). However, there was no correlation of this polymorphism found with other clinical parameters.

Conclusion: H-RAS T81C polymorphism was found to be associated with CML risk and prognosis of CML. These results suggest that C heterozygosis may be considered a potential risk factor for CML development in the North Indian population.

World J Oncol. 2015;6(2):321-328
doi: http://dx.doi.org/10.14740/wjon912e


H-RAS T81C polymorphism; Restriction fragmentation length polymorphism; H-RAS; K-RAS; N-RAS; Chronic myeloid leukemia

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