Association of MDM2 SNP309 Variation with Lung Cancer Risk: Evidence from 7196 Cases and 8456 Controls

Published on Jul 23, 2012in PLOS ONE3.24
· DOI :10.1371/JOURNAL.PONE.0041546
Wenlei Zhuo17
Estimated H-index: 17
(Third Military Medical University),
Liang Zhang9
Estimated H-index: 9
(Third Military Medical University)
+ 2 AuthorsZhengtang Chen27
Estimated H-index: 27
(Third Military Medical University)
Sources
Abstract
Background Evidence suggests that MDM2 T309G polymorphism may be a risk factor for several cancers. Increasing investigations have been conducted on the association of MDM2 T309G polymorphisms with lung cancer risk and have yielded conflicting results. Previous meta-analyses on this issue have reported inconclusive data. The aim of the present study was to derive a more precise estimation of the relationship. Methods and Findings Updated meta-analyses examining the association between MDM2 T309G polymorphism and lung cancer risk were performed. Separate analyses on ethnicity, smoking status, histological types and gender as well as source of controls were also implemented. Eligible studies were identified for the period up to Feb 2012. Lastly, ten publications including eleven case-control studies were selected for analysis. The overall data failed to indicate a significant association between MDM2 T309G polymorphism and lung cancer risk (GG vs TT OR = 1.14; 95%CI = 0.95−1.37; dominant model: OR = 1.05; 95%CI = 0.92−1.19; recessive model: OR = 1.12; 95%CI = 0.99−1.27). In a subgroup analysis by smoking status, increased lung cancer risk was shown among never-smokers (GG vs TT: OR = 1.76; 95%CI = 1.36−2.29; dominant model: OR = 1.48; 95%CI = 1.22−1.81; recessive model: OR = 1.37; 95%CI = 1.11−1.69). In subgroup analysis by gender, elevated risk was presented among women under a recessive model (OR = 1.29; 95%CI = 1.04−1.59). In the subgroup analysis by ethnicity, histological types and source of controls, no marked associations were observed. Conclusions Compared to the previous meta-analyses, the results of this study confirmed that MDM2 T309G polymorphism might be a risk factor for lung cancer among never-smokers. However, the data failed to suggest a marked association between the G allele of MDM2 T309G and lung cancer risk among Asians. More interestingly, subgroup analysis by gender indicated that homozygous GG alleles might raise lung cancer risk among females.
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A single nucleotide polymorphism (SNP) at position 309 in the promoter region of MDM2 leading to increased expression of MDM2 and attenuated function of p53 has recently been suggested as an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL) although this has been questioned. The MDM2 SNP309 genotypes in 173 CLL patients and 260 healthy controls were detected by the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method, which was confirmed by direc...
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MDM2 was originally identified as an oncoprotein that binds to p53 and inhibits p53-mediated transactivation. Scientists have described functional single-nucleotide polymorphisms (SNP) in the MDM2 gene. They showed that the genotype of SNP 309 induces an increase in the level of MDM2 protein, which causes attenuation of the p53 pathway. In this study, we sought to investigate whether this polymorphism was related to risk of colorectal cancer and whether there were relationships between SNP 309 a...
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