P53 Codon 72 and HER2 Codon 655 Polymorphisms in Turkish Breast Cancer Patients Nurten Kara, 1 Nevin Karakus, 1 Ali Naki Ulusoy, 2 Cihangir Ozaslan, 3 Bulent Gungor, 2 and Hasan Bagci 1 The polymorphisms in codon 72 of the tumor suppressor protein p53 (P53) gene and codon 655 of the human epidermal growth factor receptor 2 (HER2) gene have been suggested to play roles in most cancers. The purpose of this study was to investigate the association between common variants of HER-2 and P53 genes with breast cancer risk. Blood samples collected from 204 women with primary breast carcinoma and 192 healthy female controls were analyzed through polymerase chain reaction–restriction fragment length polymorphism methods. The frequencies of Arg=Arg, Arg=Pro, and Pro=Pro genotypes for P53 codon 72 were 51.7%, 41.4%, and 6.9% in patients and 42.6%, 47.3%, and 10.1% in controls, respectively. The frequencies of Ile=Ile, Ile=Val, and Val=Val genotypes for HER2 codon 655 were 75.0%, 22.5%, and 2.5% in patients and 73.4%, 25.0%, and 1.6% in controls, respectively. The genotype and allele frequencies between patient and control groups for P53 gene polymor- phism were not significantly different ( p ¼ 0.177 and p ¼ 0.07, respectively). Similarly, the genotype and allele frequencies between patient and control groups for HER2 gene polymorphism were not significantly different ( p ¼ 0.716 and p ¼ 0.891, respectively). With the exception of association between the P53 codon 72 polymor- phism and tumor stages ( p ¼ 0.026), there was no significant association between the studied polymorphisms and clinicopathological characteristics. The P53 gene codon 72 Arg=Pro and Her2 gene Ile655Val polymor- phisms were not associated with the risk of breast cancer in Turkish women. However, significant associa- tions between the P53 codon 72 and the homozygote and heterozygote Pro genotypes with tumor stages were found. Introduction B reast cancer is associated with different types of so- matic genetic alterations such as mutations in oncogenes and tumor suppressor genes (Turnbull and Rahman, 2008). Genetic polymorphisms at the genes involved in tumori- genesis may determine individual susceptibility to cancer (Wang et al., 1999). The tumor-suppressor protein P53 is functional in cell cycle control and apoptosis (Hartmann et al., 1997). P53 gene abnormalities are frequently associated with neoplasias, particularly breast, lung, and colon cancers (Harris, 1991). P53 codon 72 Arg=Pro (CGC to CCC) poly- morphism of exon 4 (Matlashewski et al., 1987) has been suggested to play role in several different cancer types. These two variant protein forms may behave differently, as the Arg=Arg genotype has been reported to induce apoptosis more effectively than the Pro=Pro genotype (Thomas et al., 1999; Dumont et al., 2003). In contrast, the Pro=Pro genotype appears to induce a higher level of G1 arrest than the Arg=Arg genotype (Pim and Banks, 2004; Sullivan et al., 2004). Breast cancer patients with the Pro=Pro genotype have poorer survival than those with other genotypes (Tommiska et al., 2005). The genotype distribution of P53 codon 72 poly- morphism is significantly different among ethnic groups. Meta-analysis of nine studies have recently shown that this polymorphism is not associated with breast cancer risk (Breast Cancer Association Consortium, 2006). Human epidermal growth factor receptor 2 (HER2) is a proto-oncogene that encodes a transmembrane glycoprotein with tyrosine kinase activity (Slamon et al., 1987). HER2 DNA amplification is suggested to be the principal mecha- nism of HER2=neu protein activation and is nearly always accompanied by overexpression of its protein in breast can- cer (Lee et al., 1994). Presence of a single-nucleotide poly- morphism in the transmembrane coding region of the HER2 gene at codon 655, encoding either isoleucine (Ile: ATC) or valine (val: GTC), has been reported in different cancer types (Papewalis et al., 1991; Wang et al., 2002). Changing the ex- isting isoleucine (Ile: ATC) to valine (Val: GTC) at codon 655 suggests an increased dimerization, autophosphorylation of HER2, and tyrosine kinase activity, which may cause the transformation of cells (Nakajima et al., 1999). This study was presented as a poster (P515=29=B=LB) at the XX International Congress of Genetics, Berlin, Germany, 2008. Departments of 1 Medical Biology and Genetics and 2 General Surgery, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey. 3 Department of General Surgery, Oncology Research Hospital, Ankara, Turkey. DNA AND CELL BIOLOGY Volume 29, Number 7, 2010 ª Mary Ann Liebert, Inc. Pp. 387–392 DOI: 10.1089=dna.2009.0995 387