Journal article

TheMLH1polymorphism rs1800734 and risk of endometrial cancer with microsatellite instability

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

Clinical Epigenetics | BMC | Published : 2020

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.

University of Melbourne Researchers

Grants

Awarded by Medical Research Council


Awarded by Wellcome Trust


Awarded by National Health and Medical Research Council (NHMRC)


Awarded by Health Foundation/Academy of Medical Sciences Clinician Scientist Fellowship


Awarded by NHMRC


Funding Acknowledgements

Funding for this project, AL and RT was provided by a Medical Research Council New Investigator Research Grant (MR/P000738/1). Core funding to the Wellcome Centre for Human Genetics was provided by the Wellcome Trust (090532/Z/09/Z). TAO'M is supported by a National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1111246). DNC is funded by a Cancer Research UK Advanced Clinician Scientist Fellowship and was previously supported by a Health Foundation/Academy of Medical Sciences Clinician Scientist Fellowship (C26642/A27963). ABS is supported by an NHMRC Senior Research Fellowship (APP1061779). DDB is supported by an NHMRC Career Development Fellowship (GNT1125268). GWAS and iCOGS genotyping was supported by NHMRC Project Grants (#ID1031333, ID#552402 and ID#1031333). ET is supported by grants provided by Region Stockholm (ALF project). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or the Wellcome Trust.