Background: Many breast cancers are caused by certain rare and familial mutations in the high or moderatepenetrance genes BRCA1, BRCA2 and CHEK2. The aim of this study was to examine the allele and genotypefrequencies of seven mutations in BRCA1, BRCA2 and CHEK2 genes in breast cancer patients and to investigatetheir isolated and combined associations with breast cancer risk.
Methods: We genotyped seven mutations inBRCA1, BRCA2 and CHEK2 genes and then analyzed single variations and haplotype associations in 106 breastcancer patients and 80 healthy controls.
Results: We found significant associations in the analyses of CHEK2-1100delC (p=0.001) and BRCA1-5382insC (p=0.021) mutations in breast cancer patients compared to controls.The highest risk was observed among breast cancer patients carrying both CHEK2-1100delC and BRCA2-Met784Val mutations (OR=0.093; 95%CI 0.021-0.423; p=0.001). We identified one previously undescribedBRCA2 and a CHEK2 four-marker haplotype of A-C-G-C which was overrepresented (χ2=7.655; p=0.0057)in the patient group compared to controls.
Conclusion: In this study, we identified a previously undescribedBRCA2 and CHEK2 A-C-G-C haplotype in association with the breast cancer in our population. Our resultsfurther suggest that the CHEK2-1100delC mutation in combination with BRCA2-Met784Val may lead to anunexpected high risk which needs to be confirmed in larger cohorts in order to better understand their role inthe development and prognosis of breast cancer.