Association of XRCC1 gene polymorphisms with chronic myeloid leukemia in the population of Andhra Pradesh, India.

Chronic myeloid leukemia (CML), a clonal myeloproliferative disorder, is characterized primarily by the presence of chimeric BCR-ABL oncogene, and its progression from chronic to blast phase is associated with the accumulation of additional molecular and chromosomal abnormalities. The molecular mechanisms underlying this genetic instability are poorly understood. The activity of BCR-ABL is known to be associated with the increased production of intracellular reactive oxygen species and spontaneous DNA damage, which when effected by impaired/inaccurate DNA repair systems result in increased susceptibility to CML progression. Using case-control study design, we explored possible association of the repair gene, XRCC1, particularly the codons 399, 280, and 194 polymorphisms screened through PCR-RFLP, with the CML in the sample of 350 cases (206 male and 144 female) and 350 controls from Hyderabad, the capital city of state of the Andhra Pradesh, India. The patient group constituted 301 early chronic phase cases followed by 28 accelerated and 21 blast phase cases. The median age of the patients was 42 years (range, 9-70 years). The genotype distribution revealed significant association of codons 399 (χ(2) = 11.904, degree of freedom (d.f.) = 2; P = 0.002) and 194 (χ(2) = 8.091, d.f. = 2, P = 0.017) with CML, not 280 (P = 0.29). Although these polymorphisms are known to affect the function of XRCC1, the nature and extent of their genetic association with CML does not indicate their direct role in its development. The results seem to suggest that XRCC1 gene might have an important role in CML progression but not in its causation.