High frequency of BRCA1 founder mutations in Polish women with nonfamilial breast cancer

Gaj, Paweł; Kluska, Anna; Nowakowska, Dorota; Bałabas, Aneta; Piątkowska, Magdalena; Dąbrowska, Michalina; Niwińska, Anna; Ostrowski, Jerzy

doi:10.1007/s10689-012-9560-4

Cited by 23 publications

(33 citation statements)

References 20 publications

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“…Among studied patients, at least one from nine different BRCA1 mutations was shown in over 11% of sporadic cases and 21% of familial cancers, which is in agreement with previous findings for women in Poland [28]. …”

Section: Discussionsupporting

confidence: 91%

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Common low-penetrance risk variants associated with breast cancer in Polish women

et al. 2013

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BackgroundBreast cancer is the most common type of cancer and the second leading cause of cancer-death among women in Poland. The known high-risk mutations account for 25% of familial aggregation cases and 5% of total breast cancer predisposition. Genome-wide association studies have identified a number of common low-penetrance genetic variants, but their contribution to disease risk differs between populations.MethodsTo verify selected associations with breast cancer susceptibility among Polish women, the replication study was performed, included 1424 women with breast cancer and 1788 healthy persons. Sixteen single-nucleotide polymorphisms (SNPs) were analyzed using TaqMan SNP Genotyping Assays. Allele frequency differences were tested using chi2-test implemented in PLINK v1.07 and Cochran-Armitage trend test was performed using R software.ResultsSignificant differences (Bonferroni corrected p-valuecor ≤ 0.0197) in the frequency of alleles distribution between all cancer and control subjects were observed for four (rs2736098, rs13281615, rs1219648, rs2981582) out of 16 SNPs. The same result was obtained for group of patients without high-risk BRCA1/2 mutations. The rs1219648 (p-valuecor ≤ 6.73E-03) and rs2981582 (p-valuecor ≤ 6.48E-03) SNPs showed significant association with both familial and sporadic cancers. Additionally, rs2736098 (p-valuecor ≤ 0.0234) was associated with only sporadic cancers; also in group without carriers of high-risk mutation. All these associations revealed their significance also in Cochran-Armitage trend test. Opposite to other SNPs, rs2736098 was associated with a decreased risk of breast cancer.ConclusionThe association of four known susceptibility SNPs, representing three individual loci, with breast cancer risk in Polish women was confirmed. One of them (rs2736098) seems to be specific for the Polish population. Due to the population differences in allele frequencies, identification of general genetic risk factors requires sets of association studies conducted on different populations.

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Section: Discussionsupporting

confidence: 91%

“…All patients were tested for selected pathogenic mutations in BRCA1 and BRCA2 chosen as the most frequently occurred among Polish women with breast cancer [26,28]. For BRCA1 , the whole sequence of exons 2, 5 and 20, and a part of exon 11 (nucleotides 2893 to 3502 from the beginning of this exon) were analyzed.…”

Section: Methodsmentioning

confidence: 99%

Common low-penetrance risk variants associated with breast cancer in Polish women

et al. 2013

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“…This group had a median age of 48 years (range 20–85 years); included 322, 81, and 404 HBC, HBOC, and EOBC patients, respectively; and were negative for 20 selected BRCA1/2 mutations, including 11 mutations in BRCA1 , namely, c.66_67delAG, c.181T > C, c.3756delGTCT, c.3700_3704del5, c.4035delA, c.3777delT, c.4065delTCAA, c.4041delAG, c.5263delC, c.5213G > A, and 5370C > T, and nine mutations in BRCA2 , namely, c.1408G > T, c.5946delT, c.5239insT, c.6447delTA, c.5964delAT, c.7910del5, c.9382C > T, c.8924delT, and c.9402delT [28]. …”

Section: Methodsmentioning

confidence: 99%

“…Genomic DNA was extracted from peripheral blood, as previously described [28]. DNA concentrations were determined using a Qubit 2.0 Fluorometer (Thermo) and the dsDNA HS Assay Kit (Thermo).…”

Section: Methodsmentioning

confidence: 99%

“…In a previous study, we demonstrated that in a group of 512 patients for whom targeted BRCA1/2 mutation testing did not show any pathogenic variants, sequencing of BRCA1/2 exons identified 52 carriers of mutations [28, 29]. The aim of the present study was to investigate the contribution of PALB2 germline mutations in a group of 460 BRCA1/2 -mutation negative breast and/or ovarian cancer patients and identify the optimal panel of recurrent mutations for genetic screening of PALB2 .…”

Section: Introductionmentioning

confidence: 99%

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PALB2 mutations in BRCA1/2-mutation negative breast and ovarian cancer patients from Poland

et al. 2017

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BackgroundThe PALB2 gene encodes a protein that plays a crucial role in maintaining genomic integrity. Germline inactivating mutations in PALB2 are associated with an increased risk of breast and ovarian cancer. The prevalence and spectrum of recurrent PALB2 germline mutations in breast and ovarian cancer patients from Poland is not clearly defined.Methods PALB2 exons were amplified from 460 BRCA1/2-mutation negative women with familial breast and/or ovarian cancer and early-onset breast cancer using AmpliSeq technology and sequenced on an Ion Torrent PGM sequencer. In addition, eight selected variants were genotyped using TaqMan assays in 807 BRCA1/2-mutation negative breast cancer patients and 1690 healthy women.ResultsTwo recurrent PALB2 mutations, c.172_175delTTGT and c.509_510delGA, were identified, along with one novel mutation, c.347insT. In total, PALB2 pathogenic mutations were detected in 7/460 (1.5%) patients. Furthermore, in breast and/or ovarian cancer patients, several single nucleotide variants (SNVs) were detected in the PALB2 coding region. In an additional group of 807 patients, eight (1%) carriers of two pathogenic mutations, c.172_175delTTGT (0.5%) and c.509_510delGA (0.5%), were identified. The c.509_510delGA mutation was not identified in healthy controls, while c.172_175delTTGT was identified in 4/1690 (0.24%) of control women.ConclusionsGermline mutations in the PALB2 gene were observed at a frequency of approximately 1.5% in Polish breast and/or ovarian cancer patients. Our study confirms two recurrent PALB2 mutations; c.172_175delGA and c.509_510delGA.

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Association of the BRCA1 promoter polymorphism rs11655505 with the risk of familial breast and/or ovarian cancer

et al. 2013

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Germline mutations in the BRCA1 tumor suppressor gene predispose affected individuals to breast cancer; however, incomplete cancer penetrance and the presence of phenocopies in BRCA1 families also indicate genetic and environmental modifiers of breast cancer risk. In this study, we have tested the single nucleotide polymorphism rs1655505 of the BRCA1 promoter, as candidate for the modifier of breast cancer risk. The polymorphic variants were genotyped in BRCA1-negative (729), familial breast and/or ovarian cancer cases (FBOC), including cases with a reported maternal history (154), nonfamilal (sporadic) cases (600), hereditary breast/ovarian cases with BRCA1 mutations (190) and population controls (1,590) from Central Poland. An association with the risk of FBOC was observed for the minor (T) allele and (TT) genotype (T: p = 0.006, OR = 1.40, 95% CI = 1.10-1.79; TT: p = 0.001, OR = 2.23, 95% CI = 1.37-3.62) in female cases with a reported maternal history, specifically in women with the onset of disease after 50 years of age (T: p = 0.004, OR = 1.77, 95% CI = 1.20-2.62; TT: p = 0.001, OR = 3.7, 95% CI = 1.62-8.46). The presented evidence suggests a need to conduct larger studies on the association between genetic variations at the BRCA1 promoter and the breast cancer risk, according to maternal/paternal lineage.

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High frequency of BRCA1 founder mutations in Polish women with nonfamilial breast cancer

Cited by 23 publications

References 20 publications

Common low-penetrance risk variants associated with breast cancer in Polish women

Common low-penetrance risk variants associated with breast cancer in Polish women

PALB2 mutations in BRCA1/2-mutation negative breast and ovarian cancer patients from Poland

Association of the BRCA1 promoter polymorphism rs11655505 with the risk of familial breast and/or ovarian cancer

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