Genetic variants in ATM, H2AFX and MRE11 genes and susceptibility to breast cancer in the polish population.
PBN-AR
Instytucja
Instytut Genetyki Człowieka Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
angielski
Czasopismo
BMC CANCER (30pkt w roku publikacji)
ISSN
1471-2407
EISSN
Wydawca
BIOMED CENTRAL LTD
DOI
URL
Rok publikacji
2018
Numer zeszytu
1
Strony od-do
e452 (1-11)
Numer tomu
18
Identyfikator DOI
Liczba arkuszy
1,1
Słowa kluczowe
angielski
ATM
H2AFX
MRE11
DNA repair
Breast cancer
Open access
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Wersja opublikowana
Licencja otwartego dostępu
Creative Commons — Uznanie autorstwa
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Razem z publikacją
Data udostępnienia w sposób otwarty
Streszczenia
Język
angielski
Treść
DNA damage repair is a complex process, which can trigger the development of cancer if disturbed. In this study, we hypothesize a role of variants in the ATM, H2AFX and MRE11 genes in determining breast cancer (BC) susceptibility. METHODS: We examined the whole sequence of the ATM kinase domain and estimated the frequency of founder mutations in the ATM gene (c.5932G > T, c.6095G > A, and c.7630-2A > C) and single nucleotide polymorphisms (SNPs) in H2AFX (rs643788, rs8551, rs7759, and rs2509049) and MRE11 (rs1061956 and rs2155209) among 315 breast cancer patients and 515 controls. The analysis was performed using high-resolution melting for new variants and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for recurrent ATM mutations. H2AFX and MRE11 polymorphisms were analyzed using TaqMan assays. The cumulative genetic risk scores (CGRS) were calculated using unweighted and weighted approaches. RESULTS: We identified four mutations (c.6067G > A, c.8314G > A, c.8187A > T, and c.6095G > A) in the ATM gene in three BC cases and two control subjects. We observed a statistically significant association of H2AFX variants with BC. Risk alleles (the G of rs7759 and the T of rs8551 and rs2509049) were observed more frequently in BC cases compared to the control group, with P values, odds ratios (OR) and 95% confidence intervals (CIs) of 0.0018, 1.47 (1.19 to 1.82); 0.018, 1.33 (1.09 to 1.64); and 0.024, 1.3 (1.06 to 1.59), respectively. Haplotype-based tests identified a significant association of the H2AFX CACT haplotype with BC (P <  0.0001, OR = 27.29, 95% CI 3.56 to 209.5). The risk of BC increased with the growing number of risk alleles. The OR (95% CI) for carriers of ≥ four risk alleles was 1.71 (1.11 to 2.62) for the CGRS. CONCLUSIONS: This study confirms that H2AFX variants are associated with an increased risk of BC. The above-reported sequence variants of MRE11 genes may not constitute a risk factor of breast cancer in the Polish population. The contribution of mutations detected in the ATM gene to the development of breast cancer needs further detailed study.
Cechy publikacji
oryginalna
Inne
System-identifier
PX-5add8d1bd5def64e7c7bc02c
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