The MLH1 polymorphism rs1800734 and risk of endometrial cancer with microsatellite instability

Holly Russell; Katarzyna Kedzierska; Daniel D. Buchanan; Rachael Thomas; Emma Tham; Miriam Mints; Anne Keränen; Graham G. Giles; Melissa C. Southey; Roger L. Milne; Ian Tomlinson; David Church; Amanda B. Spurdle; Tracy A. O'mara; Annabelle Lewis

doi:10.1186/s13148-020-00889-3

The MLH1 polymorphism rs1800734 and risk of endometrial cancer with microsatellite instability

Holly Russell, Katarzyna Kedzierska, Daniel D. Buchanan, Rachael Thomas, Emma Tham, Miriam Mints, Anne Keränen, Graham G. Giles, Melissa C. Southey, Roger L. Milne, Ian Tomlinson, David Church, Amanda B. Spurdle, Tracy A. O'mara, Annabelle Lewis

Medicine Monash Health

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

8 Citations (Scopus)

Abstract

Both colorectal (CRC, 15%) and endometrial cancers (EC, 30%) exhibit microsatellite instability (MSI) due to MLH1 hypermethylation and silencing. The MLH1 promoter polymorphism, rs1800734 is associated with MSI CRC risk, increased methylation and reduced MLH1 expression. In EC samples, we investigated rs1800734 risk using MSI and MSS cases and controls. We found no evidence that rs1800734 or other MLH1 SNPs were associated with the risk of MSI EC. We found the rs1800734 risk allele had no effect on MLH1 methylation or expression in ECs. We propose that MLH1 hypermethylation occurs by different mechanisms in CRC and EC.

Original language	English
Article number	102
Number of pages	9
Journal	Clinical Epigenetics
Volume	12
Issue number	1
DOIs	https://doi.org/10.1186/s13148-020-00889-3
Publication status	Published - 8 Jul 2020

Keywords

Endometrial cancer
Microsatellite instability
Mismatch repair pathway
MLH1
rs1800734
Single nucleotide polymorphism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s13148-020-00889-3Licence: CC BY

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Russell, H., Kedzierska, K., Buchanan, D. D., Thomas, R., Tham, E., Mints, M., Keränen, A., Giles, G. G., Southey, M. C., Milne, R. L., Tomlinson, I., Church, D., Spurdle, A. B., O'mara, T. A., & Lewis, A. (2020). The MLH1 polymorphism rs1800734 and risk of endometrial cancer with microsatellite instability. Clinical Epigenetics, 12(1), Article 102. https://doi.org/10.1186/s13148-020-00889-3

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abstract = "Both colorectal (CRC, 15%) and endometrial cancers (EC, 30%) exhibit microsatellite instability (MSI) due to MLH1 hypermethylation and silencing. The MLH1 promoter polymorphism, rs1800734 is associated with MSI CRC risk, increased methylation and reduced MLH1 expression. In EC samples, we investigated rs1800734 risk using MSI and MSS cases and controls. We found no evidence that rs1800734 or other MLH1 SNPs were associated with the risk of MSI EC. We found the rs1800734 risk allele had no effect on MLH1 methylation or expression in ECs. We propose that MLH1 hypermethylation occurs by different mechanisms in CRC and EC.",

keywords = "Endometrial cancer, Microsatellite instability, Mismatch repair pathway, MLH1, rs1800734, Single nucleotide polymorphism",

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AU - Russell, Holly

AU - Kedzierska, Katarzyna

AU - Buchanan, Daniel D.

AU - Thomas, Rachael

AU - Tham, Emma

AU - Mints, Miriam

AU - Keränen, Anne

AU - Giles, Graham G.

AU - Southey, Melissa C.

AU - Milne, Roger L.

AU - Tomlinson, Ian

AU - Church, David

AU - Spurdle, Amanda B.

AU - O'mara, Tracy A.

AU - Lewis, Annabelle

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AB - Both colorectal (CRC, 15%) and endometrial cancers (EC, 30%) exhibit microsatellite instability (MSI) due to MLH1 hypermethylation and silencing. The MLH1 promoter polymorphism, rs1800734 is associated with MSI CRC risk, increased methylation and reduced MLH1 expression. In EC samples, we investigated rs1800734 risk using MSI and MSS cases and controls. We found no evidence that rs1800734 or other MLH1 SNPs were associated with the risk of MSI EC. We found the rs1800734 risk allele had no effect on MLH1 methylation or expression in ECs. We propose that MLH1 hypermethylation occurs by different mechanisms in CRC and EC.

KW - Endometrial cancer

KW - Microsatellite instability

KW - Mismatch repair pathway

KW - MLH1

KW - rs1800734

KW - Single nucleotide polymorphism

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ER -

The MLH1 polymorphism rs1800734 and risk of endometrial cancer with microsatellite instability

Abstract

Keywords

UN SDGs

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Correction to: The MLH1 polymorphism rs1800734 and risk of endometrial cancer with microsatellite instability (Clinical Epigenetics, (2020), 12, 1, (102), 10.1186/s13148-020-00889-3)

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