CHEK2-positive breast cancers in young Polish women.
OBJECTIVE
To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers.


METHODS
We studied 3,228 women diagnosed with breast cancer under the age of 51 years and 5,496 population controls. CHEK2 mutations were detected by RFLP-PCR or allele-specific oligonucleotide-PCR assays. Clinical and pathologic features of CHEK2-positive cases and CHEK2-negative cases were compared.


RESULTS
A truncating CHEK2 mutation (1100delC or IVS2+1G>A) was seen in 47 of 3,228 cases and in 34 of 5,496 controls (odds ratio, 2.4; P = 0.0001). The CHEK2 I157T missense mutation was present in 207 of 3,228 cases, compared with 264 of 5,496 controls (odds ratio, 1.4; P = 0.002). Breast cancers in women with a CHEK2 mutation were more commonly of lobular histology (21.5% versus 15.8%; P = 0.05), of size >2 cm (54.8% versus 43.5%; P = 0.01), or of multicentric origin (28.7% versus 19.5%; P = 0.01) than were cancers from women without a CHEK2 mutation. Bilateral cancers were equally common in both subgroups.


CONCLUSIONS
Three founder alleles in CHEK2 contribute to early-onset breast cancer in Poland. Breast tumors which arise in carriers of CHEK2 mutations seem to be similar to those of breast cancers in the population at large.
Cybulski
Cezary
C
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. cezarycy@sci.pam.szczecin.pl
Górski
Bohdan
B
Huzarski
Tomasz
T
Byrski
Tomasz
T
Gronwald
Jacek
J
Debniak
Tadeusz
T
Wokolorczyk
Dominika
D
Jakubowska
Anna
A
Kowalska
Elzbieta
E
Oszurek
Oleg
O
Narod
Steven A
SA
Lubinski
Jan
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D064447:Checkpoint Kinase 2; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011044:Poland / Q000453:epidemiology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*
D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases