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Evidence for Selective Expression of the p53 Codon 72 Polymorphs: Implications in Cancer Development

Laboratories of ¹ Molecular Carcinogenesis, ² Molecular Genomics, ³ Clinical Pharmacology, ⁴ Photodynamic Diagnosis and Treatment, National Cancer Centre; ⁵ Department of Biochemistry, National University of Singapore, Singapore, Singapore; and ⁶ Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland

Requests for reprints: Kanaga Sabapathy, Laboratory of Molecular Carcinogenesis, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore. Phone: 65-6436-8349; Fax: 65-6226-5694. E-mail: cmrksb{at}nccs.com.sg

Polymorphism at codon 72 of p53 results in either the arginine or proline form of p53, whose functional significance in carcinogenesis is controversial. We have investigated if the expression of these p53 polymorphs is selectively regulated, using mRNA from peripheral blood of healthy Asian (Chinese) and the Caucasian (Polish) arginine/proline (arg/pro) heterozygote subjects. Asians were found to preferentially express the pro allele whereas the Caucasians preferentially express the arg allele. On the contrary, about 75% of the heterozygote Chinese breast cancer patients preferentially expressed the arg allele, which rarely contained any somatic mutations. Moreover, histologically normal tissues from Chinese heterozygote breast cancer patients showed selective expression of the arg allele, in contrast to the preferential expression of the pro allele in heterozygote healthy normal breast tissues. Together, the data suggest that the expression of the different p53 polymorphs is selectively regulated in different ethnic populations, and that the arg allele is activated during cancer development in Asians. Thus, the expression status of the p53 polymorphs, rather than the genotypic status, might be a useful indicator for cancer susceptibility.

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