The novel p21 polymorphism p21G251A is associated with locally advanced breast cancer.
OBJECTIVE
p21 is a main effector of growth arrest induced by p53. In addition, a second transcript from the same gene (p21B) has been linked to apoptosis. We previously analyzed p21 status in breast cancer and reported two novel polymorphisms of the p21 gene. In the present study, we present a larger study designed to explore a possible association between these novel polymorphisms and breast cancer.


METHODS
The p21/p21B polymorphisms were analyzed in 507 breast cancer patients and 1,017 healthy individuals using cDNA or genomic DNA from tumor and/or blood samples.


RESULTS
We detected five polymorphisms of the p21 gene. Three of these polymorphisms are earlier reported by others, whereas two were reported for the first time in a recent study by us. The presence of the A allele of the p21G251A polymorphism was observed more frequently among patients with primary stage III breast cancer (4.5%) compared with stage I and II tumors (1.5%) and healthy female controls (1.4%; P = 0.007, comparing the three groups; P = 0.0049 and P = 0.0057, comparing locally advanced to stage I/II and healthy controls, or to healthy controls alone, respectively). The allele frequencies of the remaining four polymorphisms were evenly distributed among patients and healthy individuals.


CONCLUSIONS
The finding of an association between locally advanced breast cancer and one particular polymorphism of the p21 gene suggests this polymorphism to be related to tumor behavior, including enhanced growth rate. If confirmed in other studies, this may add significant information to our understanding of the biology as well as of the clinical behaviour of locally advanced breast cancers.
Staalesen
Vidar
V
Section of Oncology, Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway.
Knappskog
Stian
S
Chrisanthar
Ranjan
R
Nordgard
Silje H
SH
Løkkevik
Erik
E
Anker
Gun
G
Ostenstad
Bjørn
B
Lundgren
Steinar
S
Risberg
Terje
T
Mjaaland
Ingvil
I
Gram
Inger Torhild
IT
Kristensen
Vessela N
VN
Børresen-Dale
Anne-Lise
AL
Lillehaug
Johan Richard
JR
Lønning
Per Eystein
PE
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012334:RNA, Neoplasm