Original Paper Prognostic Signi®cance of p53 Codon 72 Polymorphism in Lung Carcinomas Y.-C. Wang, 1 H.-S. Lee, 2 S.-K. Chen, 1 Y.-Y. Chang 1 and C.-Y. Chen 3 1 Institute of Toxicology; 2 Department of Public Health, Chung Shan Medical and Dental College, Taichung; and 3 Department of Thoracic Surgery, Taichung Veteran General Hospital, Taichung, Taiwan, Republic of China Lung cancer is the leading cause of cancer death in Taiwan. Potential molecular markers associated with cancer susceptibility and prognosis are the genes involved in tumorigenesis. Therefore, we investigated the association of p53 codon 72 polymorphism with prognosis in 114 lung cancer patients. The estimated median survival times for patients with proline (Pro)/Pro, arginine (Arg)/Arg, and Arg/ Pro genotypes were 25, 26 and 36 months, respectively. We also found that patients with the Pro/Pro genotype had a worse prognosis compared with those with Arg/Pro genotypes, especially for patients with squamous cell lung cancer (P = 0.013), male patients (P = 0.028) and those aged 60±69 years (P = 0.052). In patients with early stage lung cancer, patients with Pro/Pro and Arg/Arg genotypes had a tendency for a worse prognosis than those with the Arg/Pro genotype (P = 0.057). Our data suggest that p53 codon 72 polymorphism may be a potential prognostic factor in certain sub groups of lung cancer patients in Taiwan. # 1999 Elsevier Science Ltd. All rights reserved. Key words: lung cancer, p53 tumour suppressor gene, polymorphism, prognosis Eur J Cancer, Vol. 35, No. 2, pp. 226±230, 1999 INTRODUCTION Cancer of the lung is the leading cause of cancer death in Taiwan [1]. Lung cancer patients who undergo potentially curative resection often die due to recurrence within 5 years of resection. Patients with the same stage show varied prognoses. It is often diYcult to distinguish the patients with a poor prognosis from others with a better prognosis based on the existing diagnostic tools. Therefore, identify- ing unfavourable prognostic factors, other than the TNM system, may stimulate patients to receive adjuvant treatment. Potential molecular markers associated with cancer sus- ceptibility, as well as metastases and adverse survival, are the genes involved in tumorigenesis and/or drug metabolism. Several studies have suggested a clear genetic in¯uence on the incidence of metastases, and consequently poor prognosis, in lung cancer patients. For example, Okada and colleagues demonstrated that lymph node or distant metastasis was more frequently observed among squamous cell carcinoma (SCC) lung cancer patients with susceptible homozygous genotype C in the MspI polymorphism of the cytochrome P450 1A1 gene (CYP1A1) [2]. Goto and associates reported that lung cancer patients with a combination of susceptible CYP1A1 genotypes and a de®cient null genotype in the glu- tathione S-transferase M1 gene had remarkably shortened survivals [3]. In addition, Kawashima and co-workers found a close correlation between long band products with EcoRI restriction fragment length polymorphism of L-myc and the extent of metastasis, particularly to lymph nodes at the time of surgery [4]. Polymorphism at codon 72 in the p53 gene has been stu- died as potential susceptible genotypes for lung cancer [5±8]. The gene products of the two polymorphic variants diVer by the presence of either arginine (Arg, CGC), a large polar amino acid residue, or proline (Pro, CCC), a small, non- polar amino acid residue [9] and can be identi®ed by poly- merase chain reaction (PCR) and restriction enzyme analysis (BstUI or AccII). Association of p53 codon 72 polymorphism with lung cancer risk has been studied by several groups, although with inconsistent results. The Pro allele was found to be in excess in patients with adenocarcinoma (AD) in an American study [5]. A study carried out in Japan [6] showed European Journal of Cancer, Vol. 35, No. 2, pp. 226±230, 1999 # 1999 Elsevier Science Ltd. All rights reserved Pergamon Printed in Great Britain PII: S0959-8049(98)00369-4 0959-8049/99/$ - see front matter 226 Correspondence to C.-Y. Chen. Received 23 Jun. 1998; revised 14 Sep. 1998; accepted 21 Oct. 1998.