362 Research paper Linkage of TP53 codon 72 pro/pro genotype as predictive factor for nasopharyngeal carcinoma development Hugo Sousa a,* , Alexandra M. Santos a,* , Raquel Catarino a , Daniela Pinto a , Andre ´ Vasconcelos a , Carlos Lopes a , Eduardo Breda b and Rui Medeiros c Genetic predisposition has been suggested as a cofactor for cancer aetiology and a polymorphism in TP53 codon 72 has been associated as a susceptibility factor for several cancers. Nasopharyngeal carcinoma is a rare neoplasia in western civilizations and genetic predisposition might play an important role in its development. We evaluated the linkage of the polymorphic variants (Arg/Pro) on TP53 codon 72 with nasopharyngeal cancer development in a case–control study with 392 individuals from a northern Portuguese population, including 107 patients with nasopharyngeal carcinoma and 285 healthy controls. This study revealed a three-fold risk for carriers of Pro/Pro genotype either against carriers of Arg/Arg (OR = 2.62; 95% CI = 1.10–6.30; P = 0.016) or total Arg carriers (OR = 2.67; 95% CI = 1.21–5.90; P = 0.012). Moreover, step-wise logistic regression analysis identified Pro/Pro genotype (OR = 3.1; 95% CI = 1.3–7.3; P = 0.009), age > 49 at diagnosis (OR = 2.5; 95% CI = 1.6–4.0; P < 0.001) and male gender (OR = 2.7; 95% CI = 1.6–4.4; P < 0.001) as predictive factors for the development of nasopharyngeal carcinoma. These results confirm the data from Asiatic populations suggesting that Pro/Pro genotype represents a stable risk factor for nasopharyngeal carcinoma development in Portugal and that TP53 codon 72 polymorphism can contribute as a genetic susceptibility marker, providing additional information to improve the knowledge about nasopharyngeal carcinoma aetiology. European Journal of Cancer Prevention 15:362–366  c 2006 Lippincott Williams & Wilkins. European Journal of Cancer Prevention 2006, 15:362–366 Keywords: allele-specific-polymerase chain reaction, Epstein–Barr virus, nasopharyngeal carcinoma, TP53 codon 72 polymorphism a Molecular Oncology Unit, b Otorrinolaryngology Service, Portuguese Institute of Oncology – Oporto, Rua Dr Anto ´ nio Bernardino Almeida, Porto, Portugal and c Abel Salazar Institute for the Biomedical Sciences, Porto, Portugal Correspondence to Professor Rui Medeiros, Grupo de Oncologia e Patologia Molecular, Laborato ´ rios 4 Piso, Instituto Portugue ˆ s de Oncologia Francisco Gentil – CROP, Rua Dr Anto ´ nio Bernardino Almeida, 4200-072 Porto, Portugal Tel: + 351 22 508 4000 (ext 5414); fax: + 351 22 508 4001; e-mail: ruimedei@ipoporto.min-saude.pt We gratefully acknowledge funding of this work by the Minister of Health of Portugal (CFICS–261/99). The authors would like to thank Liga Portuguesa Contra o Cancro–Norte (Portuguese League Against Cancer) for their support. Received 24 May 2005 Accepted 16 August 2005 Introduction Nasopharyngeal carcinoma (NPC) is a rare malignancy in western countries but extremely common in south-east Asia, particularly in China, with an incidence of 20–30/ 100000 (Murray and Young, 2001; Yu and Yuan, 2002). The latest official data from 1995 points to an incidence of 0.5/100 000 cases of NPC in the northern region of Portugal (Bento, 1995). The major causal factor of NPC is the infection by a group I carcinogenic agent, the Epstein–Barr virus (EBV), one of the most common human viruses that occur worldwide (Liebowitz, 1994; Klein, 1998). Several studies suggest that EBV infection is necessary but not sufficient for NPC development (Yu, 1991; Raab-Traub, 2002). Genetic predisposition and environmental carcinogen factors are thought to be important in the aetiology of NPC (Yu, 1991; Zheng et al., 1994; Yu and Yuan, 2002). The TP53 tumour suppressor gene encodes the p53 protein, which has been described as modified in 50–55% of cancer cases (Hollstein et al., 1991). p53 has a critical function in cell cycle regulation, and in case of mutation this regulation can be lost, leading to cell proliferation without control and to the development of cancer (Vogelstein and Kinzler, 1992). The literature suggests that viral proteins can inactivate p53 through the ubiquitin pathway and also that polymorphisms on TP53 can explain individual differences in cancer development, as well as different susceptibilities to viral infections and related carcinogenesis (Nuber et al., 1998; Cooper et al., 2003; Scheffner and Whitaker, 2003). A polymorphism on codon 72 within TP53 has been reported, which encodes two distinct functional allelic forms arginine (Arg) and proline (Pro) because of a transversion G-C (Matlashewski et al., 1987; Ara et al., 1990). This polymorphism has been proposed as a genetic susceptibility factor in the development of several cancers (Birgander et al., 1995 1996; Sjalander et al., 1995a, 1996; Storey et al., 1998; Yu et al., 1999; Kawaguchi * These authors participated equally in the study. 0959-8278  c 2006 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.