MDM2 promoter polymorphism SNP309 contributes to tumor susceptibility: evidence from 21 case-control studies.
Since the identification of a well-characterized functional polymorphism named SNP309 in MDM2, abundant studies were published in the last 2 years to evaluate the association between SNP309 and tumor risk in diverse populations. However, the results remain conflicting rather than conclusive. Because a single study may have been underpowered to detect the effect of low-penetrance genes, a quantitative synthesis to accumulate data from different studies may provide better evidence on the association of genetic variant with tumor susceptibility. We conducted a meta-analysis on 14,770 cases with different tumor types and 14,524 controls from 25 published case-control studies to estimate the effect of SNP309 on tumor risk, as well as to quantify the potential between-study heterogeneity. We found that variant homozygote 309GG was associated with a significantly increased risk of all types of tumors [homozygote comparison: odds ratio (OR), 1.17, 95% confidential interval (95% CI), 1.04-1.33, P = 0.0002 for heterogeneity test; recessive model comparison: OR, 1.15, 95% CI, 1.03-1.28, P = 0.0005 for heterogeneity test]. Tumor type and ethnicity contributed to the substantial heterogeneity (69.5% for homozygote comparison and 77.2% for recessive model comparison). The analyses suggest that MDM2 SNP309 serves as a low-penetrance susceptibility tumor marker. Further large studies incorporate quantitative detection of different p53-responsible environmental stresses, p53 mutation status, and also functional genetic variants in p53-MDM2-related genes are warranted.
Hu
Zhibin
Z
Laboratory of Reproductive Medicine, Institute of Toxicology, Cancer Research Center of Nanjing Medical University, Nanjing 210029, China.
Jin
Guangfu
G
Wang
Lu
L
Chen
Feng
F
Wang
Xinru
X
Shen
Hongbing
H
D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors
D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2