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The Novel p21 Polymorphism p21^G251A Is Associated with Locally Advanced Breast Cancer

Authors' Affiliations: ¹ Section of Oncology, Department of Medicine, Haukeland University Hospital; ² Department of Molecular Biology, University of Bergen, Bergen, Norway; ³ Department of Genetics, Faculty Division, The Norwegian Radiumhospital, University of Oslo; ⁴ Department of Oncology, Rikshospitalet-Radiumhospitalet Medical Center; ⁵ Department of Oncology, Ullevål University Hospital, Oslo, Norway; ⁶ Department of Oncology, St. Olav University Hospital, Trondheim, Norway; ⁷ Department of Oncology, University Hospital of Northern Norway and Institute of Clinical Medicine, University of Tromso; ⁸ Institute of Community Medicine, University of Tromsø, Tromsø, Norway; and ⁹ Division of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway

Requests for reprints: Per Eystein Lønning, Section of Oncology, Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway. Phone: 47-55-972027; Fax: 47-55-972046; E-mail: per.lonning{at}helse-bergen.no.

Purpose: 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.

Experimental Design: 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 p21^G251A 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.

Discussion: 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.