We read with interest the paper "Association of rs2279744 and rs117039649 promoter polymorphism with the risk of gynaecological cancer" by Zhang et al. in Medicine .
In this paper, the authors assess the impact of the MDM2 promoter SNPs rs2279744 (SNP309) and rs117039649 (SNP285) on risk of gynaecological cancers by performing a meta-analysis of original case-control studies. Based on their findings, the authors conclude that both SNP309 and SNP285 are associated with risk of gynaecological cancers. While this conclusion may well be correct, we would like to raise some issues of concern.
Regarding endometrial cancer, the authors, included 6 original articles, with a total of 759 cases and 1,041 controls, omitting our study from 2012, which, as far as we know, is the largest study on SNP309 and SNP285 in endometrial cancer to date . In our study, we included 910 Caucasians diagnosed with endometrial cancer and 2,465 controls. If this data-set had been included in the meta-analysis, it would weigh more than 50% and would therefore have a major impact on the output, both in the overall assessments, and even more so in the subgroup of Caucasians. Notably, our data-set, in addition to being published in our original article , was also included in a previous meta-analysis assessing the impact of SNP309 on endometrial cancer risk .
Regarding breast cancer, the authors included 11 original articles, with a total of 3,513 cases and 3,950 controls. Here, they omitted our studies from 2011 and 2015 including 1,973 cases and 3,646 controls  and 1,717 cases and 3,749 controls , respectively.
Further, regarding ovarian cancer, the authors included 3 original articles, with a total of 599 cases and 622 controls (although these numbers must be read with caution since there are apparent errors in Table 1; reference 7 and 31 are listed with identical clinical data). Here, the authors omitted our study from 2011, including 1,993 cases and 3,646 controls . Since they cite our paper in their discussion (reference 48), we assume they are aware of its contents.
Given the number of patients enrolled in our studies mentioned above, neglecting these data-sets could seriously bias the results presented by Zhang et al. This is particularly the case for SNP285, where the data presented are from 3 studies only.
The referencing regarding identification of SNP285 is potentially misleading since the authors here refer to a previous editorial letter . This SNP was first published by the teams of Drs Lane and Thompson in Dundee, UK  along with functional and demographic characterization performed by us [4, 8, 9]. Also SNP285's role, counteracting SNP309 was described in 2011 , not in the meta-analysis given as reference 25 by Zhang et al.
Taken together, the data presented by Zhang et al might give some insight into the effects of MDM2 polymorphisms. However, due to the lack of a substantial amount of the available data published in peer-reviewed journals, their data-set may not be read as a comprehensive meta-analysis on the subject.
Stian Knappskog1,2, Liv B. Gansmo1,2 and Per E. Lønning1,2
1Section of Oncology, Department of Clinical Science, University of Bergen, Norway
2Department of Oncology, Haukeland University Hospital, Bergen, Norway
E-mail: email@example.com; firstname.lastname@example.org; email@example.com
. Zhang J, Zhang Y, Zhang Z. Association of rs2279744 and rs117039649 promoter polymorphism with the risk of gynecological cancer: A meta-analysis of case-control studies. Medicine (Baltimore). 2018;97:e9554.
. Knappskog S, Trovik J, Marcickiewicz J, et al. SNP285C modulates oestrogen receptor/Sp1 binding to the MDM2 promoter and reduces the risk of endometrial but not prostatic cancer. Eur J Cancer. 2012;48:1988-96.
. Peng Q, Mo C, Qin A, et al. MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility: evidence from a meta-analysis. J Exp Clin Cancer Res. 2013;32:85.
. Knappskog S, Bjornslett M, Myklebust LM, et al. The MDM2 Promoter SNP285C/309G Haplotype Diminishes Sp1 Transcription Factor Binding and Reduces Risk for Breast and Ovarian Cancer in Caucasians. Cancer Cell. 2011;19:273-82.
. Gansmo LB, Knappskog S, Romundstad P, et al. Influence of MDM2 SNP309 and SNP285 status on the risk of cancer in the breast, prostate, lung and colon. Int J Cancer. 2015;137:96-103.
. Knappskog S, Lonning PE. MDM2 SNP309 and risk of endometrial cancer. Pol J Pathol. 2013;64:69.
. Paulin FE, O'Neill M, McGregor G, et al. MDM2 SNP309 is associated with high grade node positive breast tumours and is in linkage disequilibrium with a novel MDM2 intron 1 polymorphism. BMC Cancer. 2008;8:281.
. Knappskog S, Gansmo LB, Dibirova K, et al. Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649). Oncotarget. 2014;5:8223-34.
. Knappskog S, Lonning PE. MDM2 promoter SNP285 and SNP309; phylogeny and impact on cancer risk. Oncotarget. 2011;2:251-8.