Genomic Instability and Cancer

The provenance of ATM candidacy as a susceptible breast cancer gene stems from two sources. The main task of ATM being that the ATM protein is a fundamental participant in mediating cellular responses to DNA damage, including cellular signaling, DNA double-strand break repair and leading to cell-cycle arrest and apoptosis. From the genetic standpoint, ATM is a gene mutated in ataxia-telangiectasia (AT), an autosomal recessive disorder phenotypically characterised by chromosomal instability and an increased risk for lymphoproliferative tumors in homozygotes. Numbers of studies have suggested that heterozygous carriers of ATM mutations are at increased risk of breast cancer and ATM IVS10-6TG SNP has been reported to significantly increase the breast cancer risk. In order to shed further light on the putative contribution of ATM to breast cancer risk, we performed haplotyping of the ATM locus in high-risk Kashmiri population. The ATM IVS10-6TG polymorphism was studied in 130 breast cancer patients and 220 female healthy controls using a PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and conformation by DNA Sequencing. The PCR-RFLP analysis revealed that 68.4% (89 of 130) breast cancer patients were homozygous for T/T variant, 21.5% (28 of 130) patients were heterozygous for T/G variant and 10% (13 of 130) patients were homozygous for GG variant. The present study concludes that the ATM IVS10-6TG polymorphism is associated with sufficiently high risk of breast cancer and among the breast cancer cases and controls the heterozygous T/G variant determines the higher risk for initiating and developing breast cancer.