SNP rs16906252C > T Is an Expression and Methylation Quantitative Trait Locus Associated with an Increased Risk of Developing MGMT-Methylated Colorectal Cancer

Joice Kuroiwa-Trzmielina; Fan Wang; Robert W Rapkins; Robyn L Ward; Daniel D Buchanan; Aung Ko Win; Mark Clendenning; Christophe Rosty; Melissa C Southey; Ingrid M Winship; John L Hopper; Mark A Jenkins; Jake Olivier; Nicholas J Hawkins; Megan P Hitchins

Journal article

SNP rs16906252C > T Is an Expression and Methylation Quantitative Trait Locus Associated with an Increased Risk of Developing MGMT-Methylated Colorectal Cancer

Joice Kuroiwa-Trzmielina, Fan Wang, Robert W Rapkins, Robyn L Ward, Daniel D Buchanan, Aung Ko Win, Mark Clendenning, Christophe Rosty, Melissa C Southey, Ingrid M Winship, John L Hopper, Mark A Jenkins, Jake Olivier, Nicholas J Hawkins, Megan P Hitchins

CLINICAL CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2016

DOI: 10.1158/1078-0432.CCR-15-2765

Abstract

PURPOSE: Methylation of the MGMT promoter is the major cause of O6-methylguanine methyltransferase deficiency in cancer and has been associated with the T variant of the promoter enhancer SNP rs16906252C>T. We sought evidence for an association between the rs16906252C>T genotype and increased risk of developing a subtype of colorectal cancer featuring MGMT methylation, mediated by genotype-dependent epigenetic silencing within normal tissues. EXPERIMENTAL DESIGN: By applying a molecular pathologic epidemiology case-control study design, associations between rs16906252C>T and risk for colorectal cancer overall, and colorectal cancer stratified by MGMT methylation status, were estimated using ..

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University of Melbourne Researchers

Daniel Buchanan Author Clinical Pathology

John Hopper Author Melbourne School of Population and Global Health

Aung Ko Win Author Melbourne School of Population and Global Health

Melissa Southey Author Clinical Pathology

Ingrid Winship Author Medicine - Royal Melbourne Hospital

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)

Awarded by Cancer Institute NSW grant

Awarded by Reserve Talents of Universities Overseas Research Program of Heilongjiang grant

Awarded by National Cancer Institute (NCI)

Awarded by Australasian Colorectal Cancer Family Registry

Awarded by NATIONAL CANCER INSTITUTE

Funding Acknowledgements

This work was supported by Australian National Health and Medical Research Council (NHMRC) grants APP568811 (M.P. Hitchins, R.L. Ward, N.J. Hawkins), APP1025799 (D.D. Buchanan, A.K. Win, M.A. Jenkins), APP1006498 (Career Development Fellowship II to M.P. Hitchins), APP1073395 (Early Career Fellowship to A.K. Win), APP1020493 (Senior Research Fellowship to M.A. Jenkins), APP1023434 (Senior Principle Research Fellowship to J.L. Hopper), Cancer Institute NSW grant RG104075 (Career Development Fellowship Top-Up Award to M.P. Hitchins), Reserve Talents of Universities Overseas Research Program of Heilongjiang grant [2013]350 (Travel Fellowship to F. Wang), and grant UM1 CA167551 from the National Cancer Institute (NCI) and through a cooperative agreement with the Australasian Colorectal Cancer Family Registry (U01 CA074778 and U01/U24 CA097735).