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Pro/Pro  genotype of p53  codon 72 polymorphism and lung cancer

Danai Tiwawech1, Adisak Sornprom2, and Anant Karalak 3

1Research, 2Surgery and 3Pathology Division, National Cancer Institute, Bangkok, Thailand.

Background: Lung cancer (LCA) is a harmful disease that caused vastly losses in Thailand yearly. The potential risk factor for screening of high-risk populations for further early stage LCA detection followed by immediately treatment is an important strategy to control this cancer. Polymorphism at codon 72 of the p53 tumor suppressor gene (p53 ) has been reported to be associated with susceptibility and prognosis of LCA. To focus on the genetic risk factor for LCA, we investigated association between the p53  codon 72 polymorphism (Proline/Arginine, Pro/Arg ) and LCA susceptibility in Thais.

Methods: DNA from peripheral blood samples of 120 lung cancer patients and 120 age-matched healthy controls was examined for genotype frequency of p53  codon 72 polymorphism (Arg/Arg, Arg/Pro  and Pro/Pro  genotype) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.

Results: Statistically significant difference in the overall genotypes between cases and controls was observed (P<0.001). The allele frequency of Pro in cases was significantly higher than controls (P<0.001). Carriers with the Pro/Pro genotype had a 6-fold increased risk for LCA when compared with those with Arg/Arg  genotype (P<0.001 with OR = 5.6, 95%CI = 2.3-13.9) but not with Arg/Pro  and Arg/Arg  + Arg/Pro  genotype. Males and females with Pro/Pro  genotype had similar risk for LCA development (OR for males : females = 5.2 : 5.1). In addition, the Pro/Pro  genotype carriers had higher risk to develop a adenocarcinoma (ACA) than squamous cell carcinoma of LCA (OR for ACA : SCC = 5.2 : 5.1). Moreover, carriers with Pro/Pro  genotype had higher risk to develop LCA stage IV than stage III (OR for stage IV : stage III = 6.9 : 4.2).

Conclusions: The results of our study suggest that the Pro/Pro  genotype of p53  codon 72 polymorphism may associate with LCA susceptibility in Thai population. The detection of p53  polymorphism may be a useful tool for screening of high-risk group, early stage detection and prognosis of LCA.

ที่มา :
การประชุมวิชาการสมาคมพิษวิทยาแห่งประเทศไทย ประจำปี 2548 Food & Chemical Safety วันที่ 17-18 พฤศจิกายน 2548 โรงแรมแกรนด์ ทาวเวอร์อินน์ ถนนพระรามหก กรุงเทพฯ