Polymorphisms in the MDM2 promoter and risk of breast cancer: a case-control analysis in a Chinese population.
MDM2 is a phosphoprotein that interacts with P53 and inhibits its activity. Recently, a T/G substitution (SNP309) in the promoter of MDM2 was identified and has been demonstrated to be associated with an increased MDM2 expression and a significantly earlier age of onset of several tumors, including breast cancer. To test the hypothesis that this functional variant in the MDM2 promoter is associated with risk of breast cancer, we conducted a molecular epidemiological study of 366 breast cancer cases (BC), 263 patients with benign breast diseases (BBD) and 605 cancer-free controls in China, in which we genotyped this T/G variant and another common insertion/deletion polymorphism (Del1518) in the MDM2 promoter and evaluated the associations between these two polymorphisms and breast cancer risk. We found that the variant allele frequencies of these two polymorphisms were not statistically different between the cases and controls (SNP309G: 0.500, 0.542, and 0.506 in BC, BBD, and controls, respectively, and Del1518-: 0.296, 0.308, and 0.297 in BC, BBD, and controls, respectively). Logistic regression analyses revealed that the variant genotypes of both MDM2 SNP309 and Del1518 polymorphisms were not significantly associated with risk of breast cancer (adjusted OR, 1.03; 95% CI, 0.74-1.42 for SNP309 TG and GG; and adjusted OR, 1.09; 95% CI, 0.83-1.43 for Del1518 +/- and -/-). These findings suggest that these two MDM2 promoter variants may not play a major role in the etiology of breast cancer.
Ma, H; Hu, Z; Zhai, X; Wang, S; Wang, X; Qin, J; Jin, G; Liu, J; Wang, X; Wei, Q; Shen, H
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