Genetic contribution to all cancers: the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology.
The aim of the study is to verify the hypothesis that genetic polymorphisms are associated with the predisposition to all malignancies. Using as a model breast cancers from the homogenous Polish population (West Pomeranian region) after stratification of 977 patients by age at diagnosis (under 51 years and above 50 years) and by tumour pathology (ductal cancers--low and high grade, lobular cancers, ER-positive/negative) we tested this hypothesis. Altogether 20 different groups of breast cancer cases have been analyzed. The results were compared to a group of unaffected controls that were matched by age, sex, ethnicity and geographical location and originated from families without cancers of any site among relatives. Molecular alterations selected for analyses included those which have been previously recognized as being associated with breast cancer predisposition. Statistically significant differences between the breast cancer cases and controls were observed in 19 of the 20 analyzed groups. Genetic changes were present in more than 90% of the breast cancer patients in 18 of 20 groups. The highest proportion of cases with constitutional changes-99.3% (139/140) was observed for lobular cancers. The number and type of genetic marker and/or the level of their association with the specific cancer predisposition was different between groups. Markers associated with majority of groups included: BRCA1, CHEK2, p53, TNRnTT, FGFRnAA, XPD CC/AA and XPD GG. Some markers appeared to be group specific and included polymorphisms in CDKN2A, CYP1B1, M3K nAA, and RS67.
Lubiński
Jan
J
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Polabska 4, 70-115, Szczecin, Poland. lubinski@sci.pam.szczecin.pl
Korzeń
Marcin
M
Górski
Bohdan
B
Cybulski
Cezary
C
Debniak
Tadeusz
T
Jakubowska
Anna
A
Jaworska
Katarzyna
K
Wokołorczyk
Dominika
D
Medrek
Krzysztof
K
Matyjasik
Joanna
J
Huzarski
Tomasz
T
Byrski
Tomasz
T
Gronwald
Jacek
J
Masojć
Bartłomiej
B
Lener
Marcin
M
Szymańska
Anna
A
Szymańska-Pasternak
Jolanta
J
Serrano-Fernàndez
Pablo
P
Piegat
Andrzej
A
Uciński
Rafał
R
Domagała
Paweł
P
Domagała
Wenancjusz
W
Chosia
Maria
M
Kładny
Józef
J
Górecka
Barbara
B
Narod
Steven
S
Scott
Rodney
R
D000367:Age Factors; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D011044:Poland; D011110:Polymorphism, Genetic
D014408:Biomarkers, Tumor; D005819:Genetic Markers