Identification of a Novel BRCA2 and CHEK2 A-C-G-C Haplotype in Turkish Patients Affected with Breast Cancer

Abstract

Background: Many breast cancers are caused by certain rare and familial mutations in the high or moderate penetrance genes BRCA1, BRCA2 and CHEK2. The aim of this study was to examine the allele and genotype frequencies of seven mutations in BRCA1, BRCA2 and CHEK2 genes in breast cancer patients and to investigate their isolated and combined associations with breast cancer risk. Methods: We genotyped seven mutations in BRCA1, BRCA2 and CHEK2 genes and then analyzed single variations and haplotype associations in 106 breast cancer 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 undescribed BRCA2 and a CHEK2 four-marker haplotype of A-C-G-C which was overrepresented (χ 2 =7.655; p=0.0057) in the patient group compared to controls. Conclusion: In this study, we identified a previously undescribed BRCA2 and CHEK2 A-C-G-C haplotype in association with the breast cancer in our population. Our results further suggest that the CHEK2-1100delC mutation in combination with BRCA2-Met784Val may lead to an unexpected high risk which needs to be confirmed in larger cohorts in order to better understand their role in the development and prognosis of breast cancer.

Molecular study of BRCA-1,2 and P53 gene polymorphisms among post-operative breast cancer patients

“…So the heterozygous AG genotype showed a statistically signi icant protective effect 16%(OR= 0.7619, 95% CI OR= (0.273 -2.125), PF=0.047), compared with control group they have (0% GG, 80% AA and 20% AG) . this result have similarity with results of (Haytural, 2013), she tested (310) patients with breast cancers were recruited from different public and private hospitals of Bangladesh and as controls (250) Bangladeshi women, and found GG genotype increase the risk of malignant tumor in breast (OR=4.9, 95% CI=0.59 to 41.09, p=0.14). So our result that is consistence with study (Hansa et al, 2012), who study on 106 consecutive breast cancer patients who were admitted to Istanbul Training and Research Hospital, Department of General Surgery and, they found GG responsible for risk to breast cancer (OR=8.54, 95% CI; 1.07-68.27).…”

Meme Kanserli̇ Hastalarda Brca1 Ve Brca2 Gen Mutasyonlarinin Değerlendi̇ri̇lmesi̇

“…185delAG mutation in BRCA1 was detected in only one patient with hereditary breast ovarian cancer syndrome from Turkish population 30 . Like our results, 6174delT mutation in BRCA2 gene were not detected in any of the studies investigating the frequencies of common BRCA1 and BRCA2 gene mutations in breast/ovarian cancer patients in Turkish population 15,[17][18][19][20][21][22][23][24]30 .…”

“…These gene mutations also have been studied in other populations in several studies [14][15][16] . In previous studies, the BRCA1 5382insC mutation has been detected in breast/ovarian cancer patients from Turkish population 15,[17][18][19][20][21][22][23][24] . However, we couldn't detect this mutation any of our early-onset breast cancer patients.…”

“…However, we couldn't detect this mutation any of our early-onset breast cancer patients. The BRCA1 5382insC mutation is mostly seen in Eastern European [25][26][27][28][29] and the patients who were found to be carrying 5382insC mutation in Turkish population are mostly from Western Turkey, near the Eastern European 15,19,21,23,24 . Also in these studies, the patients that were investigated were mainly breast/ovarian cancer patients.…”

“…Different patient selection criteria and different mutation detection methods were applied, no predominant mutation was observed in Turkish population 15,[17][18][19][20][21][22][23][24][30][31][32][33][34] .…”