eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
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vol. 64

Letter to the editor
MDM2 SNP309 and risk of endometrial cancer

Stian Knappskog
Per Eystein Lønning

Pol J Pathol 2013; 1: 69
Online publish date: 2013/04/25
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Dear Editor,

We read with interest the paper “Association between MDM2 SNP309 polymorphism and endometrial cancer risk in Polish women” by Zajac et al. in the „Polish Journal of Pathology” [1].

This paper assesses the impact of the MDM2 promoter SNP309 (rs2279744) on risk of endometrial cancer in Polish women. The data presented by the authors indicate that the SNP309G allele is associated with a severely increased risk of endometrial cancer. While their data are interesting, we need to express some concerns regarding their conclusions.

As for their results, Zajac et al. found the OR associated with the SNP309GG genotype to be 2.28 (CI: 2.02-2.54). This is a very narrow confidence interval given the limited number of observations in the study. Based on the genotype data listed in their Table II, we found SNP309G to be associated with endometrial cancer with an OR of 1.68 (95% CI: 0.89-3.17; dominant model; GG + TG vs. TT) and OR 4.67 (95% CI: 2.70-8.08; recessive model; GG vs. TG+TT).

Secondly, a potential confounding factor relates to a second MDM2 promoter SNP, SNP285G>C (rs117039649). SNP285 is located only 24 bps upstream of SNP309, and the C allele of SNP285 has been shown to counteract the effect of SNP309G: while the SNP309G allele elongates a binding site for the transcription factor Sp1, the SNP285C allele has the opposite effect, significantly reducing Sp1 binding [2]. Further, the combined SNP285C/SNP309G haplotype actually displays a weaker Sp1-transcription factor binding than the “wild-type” SNP285G/SNP309T haplotype. The SNP285C/309G haplotype accounts for about 12% of all SNP309G alleles in ~3500 North Western Europeans (Norway, the Netherlands and the UK) [3], and a similar frequency (15%) was recently reported in a cohort of 550 healthy Polish individuals [4]. Importantly, the SNP285C variant has been shown to reduce risks of breast, ovarian and endometrial cancer in large case control studies [2, 5]. Thus, to make a precise assessment of MDM2 SNP309’s impact on cancer risk, any study of this SNP in Caucasian populations should be corrected for SNP285 status in each individual.

Third, we are aware of a total of 7 previous studies reporting potential effects of the SNP309G allele on risk for endometrial cancer. In line with Zajac et al., 5 out of 7 studies report a positive association with risk for endometrial cancer while 2 showed no association. Notably, the 2...

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