Abstract
The contribution of BRCA1 and BRCA2 to breast cancer incidence in Cuba has not yet been explored. In order to estimate the proportion of breast cancers due to BRCA1 and BRCA2 mutations in Cuba, and to identify possible Cuban founder mutations, we conducted a study of unselected breast cancer patients from Havana, Cuba. We enrolled 336 women with breast cancer from a large public hospital in the city. A family history of cancer was obtained from each patient and a blood sample was processed for DNA analysis. Mutations in BRCA1 and BRCA2 were sought using a combination of techniques, but all mutations were confirmed by direct sequencing. We were able to successfully complete testing on samples from 307 women. Among these, eight mutations were identified (seven in BRCA2 and one in BRCA1) representing 2.6% of the total, including 10% of familial cases and 10% of cases under age forty. One BRCA2 mutation (c.3394C > T) was found in two women, but no clear example of a founder mutation was identified. In summary, BRCA1 and BRCA2 mutations are not uncommon in Cuban women with breast cancer, but the absence of founder mutations precludes the development of a rapid and inexpensive clinical screening test.
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References
Ford D, Easton DF, Bishop DT et al (1994) Risks of cancer in BRCA1-mutation carriers. Lancet 343:692–695
Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25:1329–1333
Antoniou A, Pharoah PD, Narod S et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130
Thompson D, Easton D, Breast Cancer Linkage Consortium (2001) Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet 68:410–419
Thompson D, Easton D, Breast Cancer Linkage Consortium (2002) Variation in BRCA1 cancer risks by mutation position. Cancer Epidemiol Biomarkers Prev 11:329–336
King M-C, Marks JH, Mandell JB, New York Breast Cancer Study Group (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302:643–646
Narod S, Ford D, Devilee P, Barkardottir RB, Eyfjord J, Lenoir G, Serova O, Easton D, Goldgar D, Breast Cancer Linkage Consortium (1997) Genetic heterogeneity of breast-ovarian cancer revisited. Am J Hum Genet 57:957–958
Narod S, Foulkes W (2004) BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer 4:665–676
Kuperstein G, Foulkes WD, Ghadirian P, Hakimi J, Narod SA (2000) A rapid fluorescent multiplexed-PCR analysis (FMPA) for founder mutations in the BRCA1 and BRCA2 genes. Clin Genet 57:213–220
BRCA1 Exon 13 Duplication Screening Group (2000) The exon 13 duplication in the BRCA1 gene is a founder mutation present in geographically diverse populations. Am J Hum Genet 67:207–212
Kuperstein G, Jack E, Risch H, McLaughlin J, Narod SA (2006) A fluorescent multiplexed-DGGE (FMD) screening test for the BRCA1 gene. Genet Test 10:1–7
Yang H, Jeffrey PD, Miller J et al (2002) BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure. Science 297:1837–1848
Hussain S, Witt E, Huber PA, Medhurst AL, Ashworth A, Mathew CG (2003) Direct interaction of the Fanconi anaemia protein FANCG with BRCA2/FANCD1. Hum Mol Genet 12:2503–2510
Sunyaev S, Ramensky V, Koch I, Lathe W, Kondrashov AS, Bork P (2001) Prediction of deleterious human alleles. Hum Mol Genet 10:591–597
Howlett NG, Taniguchi T, Olson S et al (2002) Biallelic inactivation of BRCA2 in Fanconi anemia. Science 297:606–609
Jara L, Ampuero S, Santibanez E et al (2006) BRCA1 and BRCA2 mutations in a South American population. Cancer Genet Cytogenet 166:36–45
Gallardo M, Silva A, Rubio L et al (2006) Incidence of BRCA1 and BRCA2 mutations in 54 Chilean families with breast/ovarian cancer, genotype-phenotype correlations. Breast Cancer Res Treat 95:81–87
Torres D, Rashid MU, Gil F, Umana A, Ramelli G, Robledo JF, Tawil M, Torregrosa L, Briceno I, Hamann U (2007) High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia. Breast Cancer Res Treat 103:225–232
Gomes MC, Costa MM, Borojevic R et al (2007) Prevalence of BRCA1 and BRCA2 mutations in breast cancer patients from Brazil. Breast Cancer Res Treat 103:349–353
Vega A, Campos B, Bressac-De-Paillerets B et al (2001) The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript. Hum Mutat 17:520–521
Risch HA, McLaughlin JR, Cole DEC et al (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Human Genet 68:700–710
Unger MA, Nathanson KL, Calzone K et al (2000) Screening for genomic rearrangements in families with breast and ovarian cancer identifies BRCA1 mutations previously missed by conformation-sensitive gel electrophoresis or sequencing. Am J Hum Genet 67:841–850
Walsh T, Casadei S, Coats KH et al (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295:1379–1388
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Rodriguez, R.C., Esperon, A.A., Ropero, R. et al. Prevalence of BRCA1 and BRCA2 mutations in breast cancer patients from Cuba. Familial Cancer 7, 275–279 (2008). https://doi.org/10.1007/s10689-008-9187-7
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DOI: https://doi.org/10.1007/s10689-008-9187-7