BRCA1 and BRCA2 mutations among 233 unselected Finnish ovarian carcinoma patients

Sarantaus, Laura; Vahteristo, Pia; Bloom, Elizabeth Stroh; Tamminen, Anitta; Unkila‐Kallio, Leila; Bützow, Ralf; Nevanlinna, Heli

doi:10.1038/sj.ejhg.5200652

Cited by 48 publications

(41 citation statements)

References 34 publications

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“…15 Of all BRCA1/2 mutations in Finland, the 999del5 appears to be the most common founder mutation, accounting for 17% of all BRCA1/2 families and one third of BRCA2 families. 12 In addition to Iceland and Finland, the BRCA2 999del5 mutation (reported as 995del5) has also been reported in one family of Puerto Rican origin 16 but, as yet, it…”

Section: ±13mentioning

confidence: 99%

“…Pedigree data was obtained from the Icelandic Genetic Council at the University Hospital of Iceland and verification of cancer diagnoses from the Department of Pathology, University Hospital of Iceland, and at the Icelandic Cancer Registry. Five of the families (2F, 4, 5A/ B, 6, and 7A/C) were large high risk families and 13 were pairs of sisters (2,10,13,15,16,21,23,24,32,51,57,59, and 67) diagnosed with breast cancer at the age of 60 years or younger. The Finnish 999del5 families were ascertained by four different research groups at the Helsinki, Tampere and Oulu University Hospitals by mutation screening of breast and breast-ovarian cancer families.…”

Section: Kindredsmentioning

confidence: 99%

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Haplotype analysis in Icelandic and Finnish BRCA2 999del5 breast cancer families

Barkardóttir¹,

Sarantaus

Arason

et al. 2001

Eur J Hum Genet

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The 999del5 mutation is the single, strong BRCA2 founder mutation in Iceland and the most common BRCA1/2 founder mutation in Finland. To evaluate the origin and time since spreading of the 999del5 mutation in Iceland and in Finland, we constructed haplotypes with polymorphic markers within and flanking the BRCA2 gene in a set of 18 Icelandic and 10 Finnish 999del5 breast cancer families. All Icelandic families analysed shared a common core haplotype of about 1.7 cM. The common ancestors for the Icelandic families studied were estimated to trace back to 340 ± 1000 years, not excluding the possibility that the mutation was brought to Iceland during the settlement of the country. Analysis of the Finnish families revealed two distinct haplotypes. A rare one, found in three families in the old settlement region in southwestern Finland, shared a four-marker (0.5 cM) core haplotype with the Icelandic 999del5 haplotype. A distinct *6 cM haplotype was shared by seven 999del5 Finnish families estimated to have a common ancestry 140 ± 300 years ago. These families cluster in two geographical regions in Finland, in the very same area as those with the rare haplotype and also in the most eastern, late settlement region of Finland. The results may indicate a common ancient origin for the 999del5 mutation in Iceland and in Finland, but distinct mutational events cannot be ruled out. The surprising finding of the same mutation in two completely different haplotypes in a sparsely populated area in Finland may suggest gene conversion. European Journal of Human Genetics (2001) 9, 773 ± 779.

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Section: ±13mentioning

confidence: 99%

Section: Kindredsmentioning

confidence: 99%

Haplotype analysis in Icelandic and Finnish BRCA2 999del5 breast cancer families

Barkardóttir¹,

Sarantaus

Arason

et al. 2001

Eur J Hum Genet

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“…[13][14][15][16][17][18][19], but the data from the Danish population are much more limited. The largest study of BRCA1 and BRCA2 mutations to date from Denmark is the analysis of 103 multifocal or bilateral early-onset breast cancers, which identified mutations in 20% of cases (20).…”

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confidence: 99%

BRCA1 and BRCA2 Mutation Prevalence and Clinical Characteristics of a Population-Based Series of Ovarian Cancer Cases from Denmark

Soegaard

Kjær

Cox

et al. 2008

Clinical Cancer Research

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Purpose:To evaluate the prevalence of BRCA1and BRCA2 mutations and associations with clinical correlates of disease in a population-based series of ovarian cancer cases from Denmark. Methods: DNA sequencing and multiplex ligation-dependent probe amplification analysis were used to analyze the BRCA1 and BRCA2 genes for coding sequence mutations and large genomic rearrangements in 445 confirmed cases of ovarian cancer. We evaluated associations between mutation status and clinical characteristics, including cancer risks for first-degree relatives and clinicopathologic features of tumors. Results: Deleterious BRCA1 or BRCA2 mutations were identified in 26 cases; thus, mutations in these genes are responsible for at least 5.8% of ovarian cancer cases in this population. Five different mutations were identified in more than one individual, suggesting that they may be founder mutations in Denmark. We identified several differences between mutation carriers and noncarriers: mutation carriers were diagnosed at a significantly early age (median, 49 and 61 years, respectively; P = 0.0001); the frequency of BRCA1 mutation carriers was 23% for women diagnosed <40 years,15% for 40 to 49 years, 4% for 50 to 59 years, and 2% for z60 years (P = 0.00002); ovarian cancer in carriers was diagnosed at a later stage (P = 0.002) and tumors were of poorer grade (P = 0.0001); and first-degree relatives of mutation carriers had greater relative risks of both ovarian cancer [10.6 (95% confidence interval, 4.2-26.6); P < 0.0001] and breast cancer <60 years [8.7 (95% confidence interval, 3.0-25.0); P < 0.0001].Conclusion: These data may have a significant effect on risk assessment and clinical management of individuals from Denmark who are predisposed to ovarian cancer because they carry a BRCA1 or BRCA2 mutation.

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“…The highest frequencies have been shown among Ashkenazi Jews (35 and 27%; Boyd et al, 2000;Moslehi et al, 2000) compared to 4.7 and 3.5% in the Finnish (Sarantaus et al, 2001) and British population (Stratton et al, 1997), respectively. Previously, it has been reported that 3% of Norwegian ovarian cancers are caused by BRCA1 1675delA or 1135insA (Drum et al, 1999b).…”

Section: Discussionmentioning

confidence: 97%

“…After revision of the diagnoses, we had to omit 7% of the cases since they did not meet the criteria for ovarian cancer or borderline tumours. To date, relatively few studies on BRCA mutations are population based (Risch et al, 2001;Sarantaus et al, 2001). In most studies, women are selected on the basis of a family history positive for cancer, or for early age at onset.…”

Section: Discussionmentioning

confidence: 99%

BRCA1 mutations in ovarian cancer and borderline tumours in Norway: a nested case–control study

et al. 2004

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The aims of the present study were to find the frequency of the most common BRCA1 mutations in women with ovarian tumours identified from a population-based cancer registry and in the general population, to estimate the relative risk of ovarian tumours among the mutation carriers, and to explore the value of using CA125 as a prediagnostic test. The study was designed as a nested case -control study within a cohort mainly consisting of participants in population-based health examinations. The data files of The Cancer Registry of Norway and the Janus serum bank were linked to identify cases with ovarian cancer and borderline tumours. Hereditary BRCA1 mutations were determined using archived serum samples and capillary electrophoresis. Altogether 478 ovarian cancer patients and 190 patients with borderline tumours were identified, and 1421 and 568 matching controls were selected. Odds ratios (OR) of developing ovarian cancer and borderline tumours in the presence of BRCA1 mutations and CA125 level were derived from conditional logistic regression models. Among the 478 ovarian cancer patients, 19 BRCA1 mutations were identified (1675delA, 1135insA, 816delGT and 3347delAG), none among the patients with borderline tumours. Only two of the 1989 controls were BRCA1 mutation carriers (0.10%). The risk of ovarian cancer among the mutation carriers was strongly elevated (OR ¼ 29, 95% CI ¼ 6.6 -120). CA125 was a marker for ovarian cancer, but the sensitivity was low. This study showed that BRCA1 mutation carriers have a very high risk of ovarian cancer. However, since the prevalence of BRCA1 mutations in the Norwegian population was low, the proportion of ovarian cancers due to BRCA1 mutations seemed to be low, about 4%. The sensitivity of using CA125 only as a screening test for ovarian cancer was low.

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BRCA1 and BRCA2 mutations among 233 unselected Finnish ovarian carcinoma patients

Cited by 48 publications

References 34 publications

Haplotype analysis in Icelandic and Finnish BRCA2 999del5 breast cancer families

Haplotype analysis in Icelandic and Finnish BRCA2 999del5 breast cancer families

BRCA1 and BRCA2 Mutation Prevalence and Clinical Characteristics of a Population-Based Series of Ovarian Cancer Cases from Denmark

BRCA1 mutations in ovarian cancer and borderline tumours in Norway: a nested case–control study

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