Breast cancer susceptibility genes.
In 1999 it has been recognized that 3 BRCA1 abnormalities - 5382insC, C61G and 4153delA - constitute almost 90% of all germline mutations of this gene in Poland. Due to the above findings we started performing the cheap and quick large scale testing for BRCA1 mutations and, these days, we have almost 4,000 carriers diagnosed and under direct or indirect supervision what is probably the largest number in the world. Additionally, the above results pushed us to hypothesize that genetic homogeneity will be seen in Poland in studies of other genes. Actually, the next studies allowed us to identify genes / changes associated with moderate / low breast cancer risk and showed, similarly to BRCA1, high level of genetic homogeneity. This series included BRCA2, C5972T, CHEK2 del5395; 1100delC, I157T or IVS2 + 1G > A, CDKN2A (p16) A148T, XPD Asp312Asn and Lys751Gln, CYP1B1 R48G, A119S and L43V. The results of the above studies led us in 2004 already to hypothesize that >90% of all cancers have genetic (constitutional) background. Two years later we were able to show a panel of markers covering 92% of consecutive breast cancers in Poland, and we formulated the hypothesis that all cancers have a genetic background. These days we are demonstrating for the first time that genetic components to malignancy play a role in all cancers. We are presenting it on examples of late-onset breast cancers from Poland, but it seems to be justified to expect that similar results can be achieved from other malignancies.
Lubinski
Jan
J
Pomeranian Medical University, Department of Genetics and Pathology, International Hereditary Cancer Center, Szczecin, Poland.
Korzen
Marcin
M
Gorski
Bohdan
B
Cybulski
Cezary
C
Debniak
Tadeusz
T
Jakubowska
Anna
A
Medrek
Krzysztof
K
Matyjasik
Joanna
J
Huzarski
Tomasz
T
Byrski
Tomasz
T
Gronwald
Jacek
J
Masojc
Bartlomiej
B
Lener
Marcin
M
Szymanska
Anna
A
Szymanska-Pasternak
Jolanta
J
Fernandez
Pablo Serrano
PS
Wokolorczyk
Dominika
D
Piegat
Andrzej
A
Ucinski
Michal
M
Domagala
Pawel
P
Kladny
Jozef
J
Gorecka
Barbara
B
Scott
Rodney
R
Narod
Steven
S
D001189:Aryl Hydrocarbon Hydroxylases; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D064447:Checkpoint Kinase 2; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D018703:Founder Effect; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D011044:Poland / Q000453:epidemiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human