The Association Between TP53 Arg72Pro Polymorphism and Lung Cancer Susceptibility: Evidence from 30,038 Subjects
- 329 Downloads
The TP53 codon 72 polymorphism has been associated with the individual susceptibility to lung cancer. However, the association remains uncertain and varies with ethnicity, smoking status, cancer histology, and stage.
We performed a meta-analysis to evaluate the relationship between TP53 Arg72Pro polymorphism and lung cancer susceptibility basing on 15,647 lung cancer patients and 14,391 controls from 36 published literatures. We also performed stratified analysis in populations of different ethnicities, smoking statuses, lung cancer stages, and histological types.
The analysis showed a significantly increased lung cancer susceptibility among Pro allele carriers (P < 0.001, odds ratio (OR) = 1.14, 95 % confidence interval (CI) = 1.1–1.19), especially for smokers (P < 0.001, OR = 1.29, 95 % CI = 1.12–1.47). Stratified analysis indicated that Pro72 elevates lung cancer susceptibility in Asians, while it has no effect on lung cancer risk of Caucasians. Moreover, Pro carriers present an increased risk of developing squamous cell carcinoma and adenocarcinoma, instead of large cell carcinoma and small cell carcinoma. Interestingly, patients with the Pro allele seemed to be diagnosed with lung cancer at the early stages (stage I–II, P = 0.008, OR = 1.2, 95 % CI = 1.05–1.37).
Our results suggest that the Pro allele acts as a risk factor for development of lung cancer, especially for smokers and Asians.
KeywordsTP53 Arg72Pro Lung cancer Meta-analysis
Conflict of interest
- 20.Nadji SA, Mahmoodi M, Ziaee AA, Naghshvar F, Torabizadeh J, Yahyapour Y, Nategh R, Mokhtari-Azad T (2007) An increased lung cancer risk associated with codon 72 polymorphism in the TP53 gene and human papillomavirus infection in Mazandaran province, Iran. Lung Cancer 56:145–151PubMedCrossRefGoogle Scholar
- 30.To-Figueras J, Gene M, Gomez-Catalan J, Galan C, Firvida J, Fuentes M, Rodamilans M, Huguet E, Estape J, Corbella J (1996) Glutathione-S-Transferase M1 and codon 72 p53 polymorphisms in a northwestern Mediterranean population and their relation to lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev 5:337PubMedGoogle Scholar
- 36.Zhang JH, Li Y, Wang R, Wen DG, Wu ML, He M (2003) p53 gene polymorphism with susceptibility to esophageal cancer and lung cancer in Chinese population. Zhonghua Zhong Liu Za Zhi [Chinese J Oncol] 25:365Google Scholar
- 42.Mechanic LE, Bowman ED, Welsh JA, Khan MA, Hagiwara N, Enewold L, Shields PG, Burdette L, Chanock S, Harris CC (2007) Common genetic variation in TP53 is associated with lung cancer risk and prognosis in African Americans and somatic mutations in lung tumors. Cancer Epidemiol Biomarkers Prev 16:214PubMedCrossRefGoogle Scholar
- 43.Popanda O, Edler L, Waas P, Schattenberg T, Butkiewicz D, Muley T, Dienemann H, Risch A, Bartsch H, Schmezer P (2007) Elevated risk of squamous-cell carcinoma of the lung in heavy smokers carrying the variant alleles of the TP53 Arg72Pro and p21 Ser31Arg polymorphisms. Lung Cancer 55:25–34PubMedCrossRefGoogle Scholar
- 52.Ihsan R, Devi TR, Yadav DS, Mishra AK, Sharma J, Zomawia E, Verma Y, Phukan R, Mahanta J, Kataki AC (2011) Investigation on the role of p53 codon 72 polymorphism and interactions with tobacco, Betel Quid, and alcohol in susceptibility to cancers in a high-risk population from North East India. DNA Cell Biol 30:317–324Google Scholar
- 54.Hung RJ, Boffetta P, Canzian F, Moullan N, Szeszenia-Dabrowska N, Zaridze D, Lissowska J, Rudnai P, Fabianova E, Mates D (2006) Sequence variants in cell cycle control pathway, X-ray exposure, and lung cancer risk: a multicenter case-control study in Central Europe. Cancer Res 66:8280–8286PubMedCrossRefGoogle Scholar
- 58.Liu D, Wang F, Guo X, Wang Q, Wang W, Xu H, Xu G (2012) Association between p53 codon 72 genetic polymorphisms and tobacco use and lung cancer risk in a Chinese population. Mol Biol Rep 40:1–5Google Scholar