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

Reham Helwa; Liv B Gansmo; Merete Bjørnslett; Mari Kyllesø Halle; Henrica M J Werner; Pål Romundstad; Kristian Hveem; Lars Vatten; Anne Dørum; Per E Lønning; Stian Knappskog

doi:10.1080/1354750x.2021.1891291

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

Reham Helwa, Liv B Gansmo, Merete Bjørnslett, Mari Kyllesø Halle, Henrica M J Werner, Pål Romundstad, Kristian Hveem, Lars Vatten, Anne Dørum, Per E Lønning, Stian Knappskog^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	302-308
Number of pages	7
Journal	Biomarkers
Volume	26
Issue number	4
DOIs	https://doi.org/10.1080/1354750x.2021.1891291
Publication status	Published - 19 May 2021

Keywords

Aged
Alleles
Case-Control Studies
Cohort Studies
Endometrial Neoplasms/diagnosis
Female
Gene Frequency
Genetic Predisposition to Disease/genetics
Genome-Wide Association Study/methods
Genotype
Humans
Linkage Disequilibrium
Middle Aged
Ovarian Neoplasms/diagnosis
Polymorphism, Single Nucleotide
Promoter Regions, Genetic/genetics
Proto-Oncogene Proteins c-mdm2/genetics
ovarian cancer
polymorphism
POLYMORPHISM
SNP
MDM2
endometrial cancer
risk

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10.1080/1354750x.2021.1891291Licence: CC BY-NC-ND

Cite this

@article{71224eab0f88490d89c2f92d2f526f37,

title = "Impact of MDM2 promoter SNP55 (rs2870820) on risk of endometrial and ovarian cancer",

abstract = "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.",

keywords = "Aged, Alleles, Case-Control Studies, Cohort Studies, Endometrial Neoplasms/diagnosis, Female, Gene Frequency, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study/methods, Genotype, Humans, Linkage Disequilibrium, Middle Aged, Ovarian Neoplasms/diagnosis, Polymorphism, Single Nucleotide, Promoter Regions, Genetic/genetics, Proto-Oncogene Proteins c-mdm2/genetics, ovarian cancer, polymorphism, POLYMORPHISM, SNP, MDM2, endometrial cancer, risk",

author = "Reham Helwa and Gansmo, {Liv B} and Merete Bj{\o}rnslett and Halle, {Mari Kylles{\o}} and Werner, {Henrica M J} and P{\aa}l Romundstad and Kristian Hveem and Lars Vatten and Anne D{\o}rum and L{\o}nning, {Per E} and Stian Knappskog",

note = "Funding Information: This study was supported by funding from the Norwegian Cancer Society, the Norwegian Health Region West, the Norwegian Research Council, the Bergen Research Foundation, and the K.G. Jebsen Foundation. The authors thank Beryl Leirvaag for technical assistance. The majority of this work was performed in the Mohn Cancer Research Laboratory. We also gratefully acknowledge the Ovarian Cancer Association Consortium (OCAC). Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

year = "2021",

month = may,

day = "19",

doi = "10.1080/1354750x.2021.1891291",

language = "English",

volume = "26",

pages = "302--308",

journal = "Biomarkers",

issn = "1354-750X",

publisher = "Routledge/Taylor & Francis Group",

number = "4",

}

TY - JOUR

T1 - Impact of MDM2 promoter SNP55 (rs2870820) on risk of endometrial and ovarian cancer

AU - Helwa, Reham

AU - Gansmo, Liv B

AU - Bjørnslett, Merete

AU - Halle, Mari Kyllesø

AU - Werner, Henrica M J

AU - Romundstad, Pål

AU - Hveem, Kristian

AU - Vatten, Lars

AU - Dørum, Anne

AU - Lønning, Per E

AU - Knappskog, Stian

N1 - Funding Information: This study was supported by funding from the Norwegian Cancer Society, the Norwegian Health Region West, the Norwegian Research Council, the Bergen Research Foundation, and the K.G. Jebsen Foundation. The authors thank Beryl Leirvaag for technical assistance. The majority of this work was performed in the Mohn Cancer Research Laboratory. We also gratefully acknowledge the Ovarian Cancer Association Consortium (OCAC). Publisher Copyright: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

PY - 2021/5/19

Y1 - 2021/5/19

N2 - 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.

AB - 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.

KW - Aged

KW - Alleles

KW - Case-Control Studies

KW - Cohort Studies

KW - Endometrial Neoplasms/diagnosis

KW - Female

KW - Gene Frequency

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study/methods

KW - Genotype

KW - Humans

KW - Linkage Disequilibrium

KW - Middle Aged

KW - Ovarian Neoplasms/diagnosis

KW - Polymorphism, Single Nucleotide

KW - Promoter Regions, Genetic/genetics

KW - Proto-Oncogene Proteins c-mdm2/genetics

KW - ovarian cancer

KW - polymorphism

KW - POLYMORPHISM

KW - SNP

KW - MDM2

KW - endometrial cancer

KW - risk

U2 - 10.1080/1354750x.2021.1891291

DO - 10.1080/1354750x.2021.1891291

M3 - Article

C2 - 33645339

SN - 1354-750X

VL - 26

SP - 302

EP - 308

JO - Biomarkers

JF - Biomarkers

IS - 4

ER -