Hereditary Cancer in Clinical Practicevolume 6, Article number: 81 (2008)
Mutations in BRCA1 confer a high lifetime risk for both breast and ovarian cancer. Many different BRCA1 mutations have been described in families with early-onset breast and ovarian cancer [1, 2]. The presence of recurrent mutations in BRCA1 suggests the presence of founder effects. BRCA1 "de novo" mutations are very rare. 66 families were studied in Szczecin with strong aggregations of breast/ovarian cancers. Mutations were found in 35 (53%) of the 66 families. Three BRCA1 abnormalities - 5382insC, C61G, and 4153delA - accounted for 51, 20, and 11% of the identified mutations, respectively . Similar results were reported in Gliwice, Gdańsk and Poznań centres [4–6]. Additional evaluation of 200 families originating from all regions of Poland (with at least 3 breast/ovarian cancers) revealed that constitutional BRCA1 mutations can be detected in 64% (128/200) of these families, and 90% of all of them carried one of the 3 common founder mutations (5382insC, C61G and 4153delA) . Genetic testing for these BRCA1 mutations is inexpensive and relatively simple in Poland (~100 Euro including genetic counselling). It is based on the "multiplex PCR" method with almost 100% specificity in detection of three common Polish BRCA1 mutations. In 2006, 3500 unselected incident cases of early-onset breast cancers were screened for presence of the three common Polish BRCA1 mutations. The proportion of cases with an identified mutation was 5.7% . In a similar study of 500 unselected ovarian cancers, common BRCA1 mutations were detected in 13% of cases [9, 10]. It is possible to increase women's awareness about hereditary cancer through the popular press. Genetic testing was offered to 5000 Polish women through an announcement placed in a popular women's magazine „Twój Styl”. A total of 5024 women who qualified received a free genetic test for three mutations in BRCA1 which are common in Poland. Out of these, 198 women (3.9%) were found to carry a BRCA1 mutation. Genetic testing for BRCA1 mutations in Poland should be recommended for adult females who:
fulfil clinical criteria of hereditary breast/ovarian cancer,
are affected with breast or ovarian cancer,
are healthy but have at least one relative with breast/ovarian cancer (breast cancer diagnosed under age 50).
Genetic testing for presence of BRCA1 mutations should be preceded and followed by genetic counselling. So far nearly 4500 BRCA1 mutation carriers have been detected at the International Hereditary Cancer Centre in Szczecin (the world's largest registry of females diagnosed and under surveillance by a single centre).
We believe that the "Polish model" of solving the problem of BRCA1/BRCA2 testing can be valuable for many populations with a relatively high level of genetic homogeneity.
Chamberlain JS, Boehnke M, Frank TS, Kiousis S, Xu J, Guo S-W, Hauser R, Norum RA, Helmbold EA, Markel DS, Keshavarzi SM, Jackson CE, Calzone K, Garber J, Collins FS, Weber BL: BRCA1 maps proximal to D178579 on chromosome 17q21 by genetic analysis. Am J Hum Genet 1993, 52: 792–798.
Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal J, Hussey C, Tran T, McClure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Ward J, Tonin P, Narod S, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barrett JC, Lewis C, Neuhausen S, Cannon-Albright L, Goldgar D, Wiseman R, Kamb A, Skolnick MH: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994, 266: 66–71. 10.1126/science.7545954
Górski B, Byrski T, Huzarski T, Jakubowska A, Menkiszak J, Gronwald J, Płużanska A, Bębenek M, Fischer-Maliszewska L, Grzybowska E, Narod SA, Lubiński J: Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer. Am J Hum Genet 2000, 66: 1963–1968. 10.1086/302922
Grzybowska E, Zientek H, Jasinska A, Rusin M, Kozlowski P, Sobczak K, Sikorska A, Kwiatkowska E, Gorniak L, Kalinowska E, Utracka-Hutka B, Wloch J, Chmielik E, Krzyzosiak WJ: High frequency of recurrent mutations in BRCA1 and BRCA2 genes in Polish families with breast and ovarian cancer. Hum Mut 2000, 16: 482–490. 10.1002/1098-1004(200012)16:6<482::AID-HUMU5>3.0.CO;2-O
Sobczak K, Kozłowski P, Napierała M, Czarny J, Woźniak M, Kapuścińska M, Lośko M, Koziczak M, Jasińska A, Powierska J, Braczkowski R, Breborowicz J, Godlewski D, Mackiewicz A, Krzyzosiak W: Novel NRCA1 mutations and more frequent intron-20 alteration found among 236 women from Western Poland. Oncogene 1997, 15: 1773–1779. 10.1038/sj.onc.1201360
Looij M, Wysocka B, Brozek I, Jassem J, Limon J, Olah E: Founder BRCA1 mutation and two novel germline BRCA2 mutations in breast and/or ovarian cancer families from NorthEastern Poland. Hum Mutat 2000, 15: 480–481. 10.1002/(SICI)1098-1004(200005)15:5<480::AID-HUMU13>3.0.CO;2-G
Górski B, Jakubowska A, Huzarski T, Byrski T, Gronwald J, Grzybowska E, Mackiewicz A, Stawicka M, Bebenek M, Sorokin D, Fiszer-Maliszewska Ł, Haus O, Janiszewska H, Niepsuj S, Góźdź S, Zaremba L, Posmyk M, Płuzańska M, Kilar E, Czudowska D, Waśko B, Miturski R, Kowalczyk JR, Urbański K, Szwiec M, Koc J, Debniak B, Rozmiarek A, Debniak T, Cybulski C, Kowalska E, Tołoczko-Grabarek A, Zajaczek S, Menkiszak J, Medrek K, Masojć B, Mierzejewski M, Narod SA, Lubiński J: A high proportion of founder BRCA1 mutations in Polish breast cancer families. Int J Cancer 2004, 110: 683–686. 10.1002/ijc.20162
Lubiński J, Górski B, Huzarski T, Byrski T, Gronwald J, Serrano-Fernández P, Domagała W, Chosia M, Uciński M, Grzybowska E, Lange D, Maka B, Mackiewicz A, Karczewska A, Breborowicz J, Lamperska K, Stawicka M, Gozdecka-Grodecka S, Bebenek M, Sorokin D, Wojnar A, Haus O, Sir J, Mierzwa T, Niepsuj S, Gugała K, Góźdź S, Sygut J, Kozak-Klonowska B, Musiatowicz B, Posmyk M, Kordek R, Morawiec M, Zambrano O, Waśko B, Fudali L, Skret J, Surdyka D, Urbański K, Mituś J, Ryś J, Szwiec M, Rozmiarek A, Dziuba I, Wandzel P, Wiśniowski R, Szczylik C, Kozak A, Kozłowski W, Narod SA: BRCA1-positive breast cancers in young women from Poland. Breast Cancer Res Treat 2006, 99: 71–76. 10.1007/s10549-006-9182-3
Menkiszak J, Gronwald J, Górski B, Jakubowska A, Huzarski T, Byrski T, Foszczyńska-Kłoda M, Haus O, Janiszewska H, Perkowska M, Brozek I, Grzybowska E, Zientek H, Góźdź S, Kozak-Klonowska B, Urbański K, Miturski R, Kowalczyk J, Pluzańska A, Niepsuj S, Koc J, Szwiec M, Drosik K, Mackiewicz A, Lamperska K, Strózyk E, Godlewski D, Stawicka M, Waśko B, Bebenek M, Rozmiarek A, Rzepka-Górska I, Narod SA, Lubiński J: Hereditary ovarian cancer in Poland. Int J Cancer 2003, 106: 942–945. 10.1002/ijc.11338
Ratajska M, Brozek I, Senkus-Konefka E, Jassem J, Stepnowska M, Palomba G, Pisano M, Casula M, Palmieri G, Borg A, Limon J: BRCA1 and BRCA2 point mutations and large rearrangements in breast and ovarian cancer families in Northern Poland. Oncol Rep 2008, 19: 263–268.