Impact of MDM2 promoter SNP55 (rs2870820) on risk of endometrial and ovarian cancer

Background While large GWAS analyses have not found convincing associations between MDM2 promoter SNP55 and gynaecological cancers, SNP55 is in linkage disequilibrium with two other functional SNPs in the same promoter, likely to obscure associations between single SNPs and cancer risk. Here, we assessed the impact of SNP55 on risk of endometrial and ovarian cancer, including sub-analyses stratified for other functional SNPs in the region. Material and methods Using a custom LightSNiP assay, we genotyped SNP55 in two large hospital-based cohorts of patients with ovarian (n = 1,332) and endometrial (n = 1,363) cancer and compared genotypes to healthy female controls (n = 1,858). Results Among individuals harbouring the SNP309TT genotype, the minor SNP55T-allele was associated with a reduced risk of endometrial (dominant model: OR = 0.63; CI = 0.45-0.88; p = 0.01). Regardless of the genotype in neighbouring SNPs, the SNP55T-allele was also associated with a reduced risk of endometrial cancer before 50 years of age (dominant model: OR = 0.56; CI = 0.34-0.90; p = 0.02). No association between SNP55 status and ovarian cancer risk was observed. Conclusions MDM2 SNP55T-allele may correlate with reduced risk for endometrial cancer in a SNP309T-, but not SNP309G, context.

Automated summary

The study found that the MDM2 SNP55T allele may be associated with a reduced risk of endometrial cancer when combined with the SNP309TT genotype, but not in the context of SNP309G. Additionally, the SNP55T allele was also associated with a reduced risk of endometrial cancer in individuals under 50 years old, regardless of the genotype in neighboring SNPs. No association was observed between SNP55 status and ovarian cancer risk.