The contribution of founder mutations in <i>BRCA1</i> to breast cancer in Belarus

Uglanitsa, N; Oszurek, Oleg; Uglanitsa, K; Savonievich, E; Lubiński, Jan; Cybulski, Cezary; Dębniak, Tadeusz; Narod, SA; Gronwald, Jacek

doi:10.1111/j.1399-0004.2010.01439.x

Cited by 23 publications

(17 citation statements)

References 12 publications

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“…For high risk families of this origin, the rates of the predominant mutations in BRCA1 in the present study are 1.1% (C61G) and 0.7% (4153delA). These data are in line with data reported on non Jewish high risk families from Russia [16] Poland [14,15] and the Baltic republics [17,18]. Thus, for these unique non Jewish high risk families, these two mutations should be offered in the course of oncogenetics counseling and testing in Israel, prior to offering full mutational analysis of both genes.…”

Section: Discussionsupporting

confidence: 86%

“…A sizeable portion of these immigrants (estimated at 50%) are of Russian non Jewish origin. Two recurring mutations in BRCA1 in Russian and Baltic region high risk families have been reported: 5382InsC and 4153delA in BRCA1 [14][15][16][17][18]. In addition, the C61G is a mutation frequently detected in non Jewish Polish high risk families [14,15] and rarely in non Ashkenazi Jews [19].…”

Section: Introductionmentioning

confidence: 99%

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Recurrent germline mutations in BRCA1 and BRCA2 genes in high risk families in Israel

Laitman

Simeonov

Herskovitz

et al. 2012

Breast Cancer Res Treat

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The spectrum of germline mutations among Jewish non Ashkenazi high risk breast/ovarian cancer families includes a few predominant mutations in BRCA1 (185delAG and Tyr978X) and BRCA2 (8765delAG). A few additional recurring mutations [A1708E, 981delAT, C61G (BRCA1) R2336P, and IVS2 + 1G > A (BRCA2)] have been reported in Jewish non Ashkenazi families. The 4153delA*BRCA1 C61G*BRCA1 and the 4075delGT*BRCA2 has been reported to recur in Russian/Polish non Jews and Ashkenazim, respectively. The rate of these recurring mutations has not been reported in Israeli high risk families. Genotyping for these recurring mutations by restriction enzyme digest and sequencing method was applied to high risk, predominantly cancer affected, unrelated Israeli individuals of Ashkenazi (n = 827), non Ashkenazi (n = 2,777), non Jewish Caucasians (n = 193), and 395 of mixed ethnicity. Jewish participants included 827 Ashkenazi, 804 Balkans, 847 North Africans, 234 Yemenites, and 892 Asians (Iraq and Iran). Age at diagnosis of breast cancer (median ± SD) (n = 2,484) was 47.2 ± 9.6 for all women participants. Males (n = 236) were also included, of whom 24 had breast cancer and 35 had pancreatic cancer. Overall, 8/282 (2.8%) of the Balkan cases carried the BRCA1*A1708E mutation, 4/180 (2.2%) the R2336P mutation, and 0/270 the IVS2 + 1G > A BRCA2 mutations, respectively. Of North Africans, 7/264 (2.65%) carried the BRCA1*981delAT mutation. The BRCA1*C61G mutation was detected in 3/269 Ashkenazi, non Ashkenazi, and non Jewish Russians; the BRCA1*Tyr978X mutation was detected in 23/3220 individuals of non Ashkenazi origin, exclusively of Asian ethnicity (23/892, 2.6% of the Asians tested). The BRCA1*4153delA mutation was noted in 2/285 non Jewish Caucasians, and none of the Ashkenazim (n = 500) carried the BRCA2*4075delGT mutation. Jewish high risk families of North African, Asian, and Balkan descent should be screened for the 981delAT, Tyr978X, A1708E BRCA1, and the R2336P BRCA2 mutations, respectively.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Recurrent germline mutations in BRCA1 and BRCA2 genes in high risk families in Israel

Laitman

Simeonov

Herskovitz

et al. 2012

Breast Cancer Res Treat

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“…Interestingly, the p.Cys61Gly and 5266dup BRCA1 PSVs, seem to be the most prevalent PSVs in the present study, and were reported in 11 and 16 countries, respectively. These are the most common PSVs in Poland (Górski et al, ) and other geographically related countries like Belarus (Uglanitsa et al, ). The prevalence and distribution of these PSVs in countries from the Middle East and North Africa, a region for which there is no recorded massive population exchange or North European influx is puzzling.…”

Section: Discussionmentioning

confidence: 99%

The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in Middle Eastern, North African, and South European countries

et al. 2019

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BRCA1 BRCA2 mutational spectrum in the Middle East, North Africa, and Southern Europe is not well characterized. The unique history and cultural practices characterizing these regions, often involving consanguinity and inbreeding, plausibly led to the accumulation of population‐specific founder pathogenic sequence variants (PSVs). To determine recurring BRCA PSVs in these locales, a search in PUBMED, EMBASE, BIC, and CIMBA was carried out combined with outreach to researchers from the relevant countries for unpublished data. We identified 232 PSVs in BRCA1 and 239 in BRCA2 in 25 of 33 countries surveyed. Common PSVs that were detected in four or more countries were c.5266dup (p.Gln1756Profs), c.181T>G (p.Cys61Gly), c.68_69del (p.Glu23Valfs), c.5030_5033del (p.Thr1677Ilefs), c.4327C>T (p.Arg1443Ter), c.5251C>T (p.Arg1751Ter), c.1016dup (p.Val340Glyfs), c.3700_3704del (p.Val1234Glnfs), c.4065_4068del (p.Asn1355Lysfs), c.1504_1508del (p.Leu502Alafs), c.843_846del (p.Ser282Tyrfs), c.798_799del (p.Ser267Lysfs), and c.3607C>T (p.Arg1203Ter) in BRCA1 and c.2808_2811del (p.Ala938Profs), c.5722_5723del (p.Leu1908Argfs), c.9097dup (p.Thr3033Asnfs), c.1310_1313del (p. p.Lys437Ilefs), and c.5946del (p.Ser1982Argfs) for BRCA2. Notably, some mutations (e.g., p.Asn257Lysfs (c.771_775del)) were observed in unrelated populations. Thus, seemingly genotyping recurring BRCA PSVs in specific populations may provide first pass BRCA genotyping platform.

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“…There appeared to be differences in the relative contribution of these mutations to breast or ovarian cancer, respectively. The high frequency of carriers may have important clinical consequences for early detection and tailored therapies to combat BRCA1 associated cancers in this population (35).…”

Section: Discussionmentioning

confidence: 99%

High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus

Bogdanova

Antonenkova²,

Rogov

et al. 2010

Clinical Genetics

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Bogdanova NV, Antonenkova NN, Rogov YI, Karstens JH, Hillemanns P, Dörk T. High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus. Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital‐based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first‐degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first‐degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non‐carriers. Taken together, these results identify three BRCA1 founder mutations as key components of inherited breast and ovarian cancer susceptibility in Belarus and might have implications for cancer prevention, treatment and genetic counselling in this population.

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The contribution of founder mutations in BRCA1 to breast cancer in Belarus

Cited by 23 publications

References 12 publications

Recurrent germline mutations in BRCA1 and BRCA2 genes in high risk families in Israel

Recurrent germline mutations in BRCA1 and BRCA2 genes in high risk families in Israel

The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in Middle Eastern, North African, and South European countries

High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus

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