Study of Atm and Chek2 Genes Snps and Their Association with Breast Cancer

Abstract

To analyze ATM and CHEK2 genes for the presence of SNPs and their association with breast cancer. Breast cancer is a malignant tumour that starts in the cells of the breast. 10-15% of breast cancer cases have some family history of the disease, only 5% can be explained by rare, highly penetrant mutations in genes such as BRCA1 and BRCA2 (First-degree relatives of breast cancer patients have a 2-fold increase in risk over the general population). Breast cancer can be separated into different types based on the way the cancer cells look under the microscope. Risk factors could be genetic or environmental, or in most cases, a combination of the two.  The higher rate of most breast cancers in monozygotic twins of case patients than in dizygotic twins or siblings suggests that most familial clustering is the result of inherited genetic factors rather than lifestyle or environmental factors. Some of this clustering can be explained by mutations in specific genes that confer high risk of disease. However, such susceptibility alleles are rare in the population. For example, highly penetrant variants in the breast cancer susceptibility genes BRCA1 and BRCA2 account for less than 20% of the total genetic risk of breast cancer and other, rarer high-penetrance genes such as TP53 and PTEN account for less than 5% of the risk. It is likely that much of the unexplained familial risk is due to alleles of low to moderate penetrance. The ability to identify such genetic variants can be further improved by careful selection of both candidate gene and candidate polymorphism. The study involves 50 breast cancer cases and 50 control subjects. The SNP 5144 A>T in ATM promoter was examined by PCR-RFLP using FokI restriction enzyme and gel electrophoresis. The SNP 1100del C>G in CHEK 2 was examined by allele specific PCR followed by gel electrophoresis. The genotypes were determined and compared between patients and controls and the effect of polymorphism on clinicopathological data of breast cancer patients was studied. The frequencies of del/C and del/del genotypes of CHEK2 delC polymorphism and AT and T allele of ATM -5144A>T polymorphism had shown an elevation with respect to clinical variables of breast cancer such as tumor stage, tumor type and ER/PR status even though there was no significant difference in the genotype distribution between cases and controls.