Association between a functional single nucleotide polymorphism in the MDM2 gene and sporadic endometrial cancer risk.
OBJECTIVE
MDM2 is an important negative regulator of the p53 tumor suppressor protein. A naturally occurring T/G single nucleotide polymorphism (SNP) in the MDM2 gene promoter, SNP309, causes an increase in MDM2 protein levels and impairment of p53 tumor suppressor activity. SNP309 occurs at a relatively high frequency in the general population and has been associated with accelerated tumorigenesis in hereditary Li-Fraumeni associated cancers as well as in sporadic soft tissue sarcomas. The objective of this study was to examine the association between SNP309 and sporadic endometrial cancer risk.


METHODS
Genomic DNA was isolated from 73 patients with endometrial cancer and 79 healthy, female controls. The MDM2 gene promoter region was amplified by PCR and the SNP309 genotype determined by restriction enzyme digestion of the amplified DNA fragment. Unconditional logistic regression analysis was used to determine the relationship between genotypes and endometrial cancer risk and histopathologic features.


RESULTS
The homozygous G/G genotype was found in 25% of endometrial cancer cases and 11% of controls. In an age-adjusted analysis of cases and controls, the G/G genotype increased the risk of endometrial cancer 2.76-fold (95% CI: 1.06, 7.20; p=0.03) compared to presence of a wild-type T allele (T/G and T/T genotypes). No association was found between the SNP309 G/G genotype and either endometrial cancer histology, grade, stage, or age at diagnosis.


CONCLUSIONS
The MDM2 SNP309 homozygous G/G genotype may be a genetic variant that influences sporadic endometrial cancer susceptibility.
Walsh
Christine S
CS
Department of Obstetrics and Gynecology, Cedars-Sinai Women's Cancer Research Institute, David Geffen School of Medicine at UCLA, 8700 Beverly Boulevard, Suite 290W, Los Angeles, CA 90048, USA. walshc@cshs.org
Miller
Carl W
CW
Karlan
Beth Y
BY
Koeffler
H Phillip
HP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*
D004273:DNA, Neoplasm; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2