MLH1 Region Polymorphisms Show a Significant Association with CpG Island Shore Methylation in a Large Cohort of Healthy Individuals

PLoS ONE

Volumn 7, Issue 12, 2012, Pages

  Savio, Andrea J ^a,b   Lemire, Mathieu ^c   Mrkonjic, Miralem ^a,b   Gallinger, Steven ^a,b,d   Zanke, Brent W ^e   Hudson, Thomas J ^c   Bapat, Bharati ^a,b,f  

^a UNIVERSITY OF TORONTO   (Canada)

^b MOUNT SINAI HOSPITAL   (Canada)

^c ONTARIO INSTITUTE FOR CANCER RESEARCH   (Canada)

^d CANCER CARE ONTARIO   (Canada)

^e OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^f UNIVERSITY HEALTH NETWORK   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN MLH1;

ADULT; ARTICLE; CHROMOSOME 3P; COHORT ANALYSIS; COLON CARCINOGENESIS; COLORECTAL CANCER; CONTROLLED STUDY; CPG ISLAND; DNA METHYLATION; FEMALE; GENE FREQUENCY; GENETIC ASSOCIATION; GENETIC VARIABILITY; HETEROZYGOTE; HOMOZYGOTE; HUMAN; HUMAN CELL; MAJOR CLINICAL STUDY; MALE; MICROARRAY ANALYSIS; MICROSATELLITE INSTABILITY; MLH1 GENE; PERIPHERAL BLOOD MONONUCLEAR CELL; SEX DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; WILD TYPE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; AGED; BLOOD CELLS; CELL TRANSFORMATION, NEOPLASTIC; COLORECTAL NEOPLASMS; CPG ISLANDS; DNA METHYLATION; FEMALE; GENETIC ASSOCIATION STUDIES; GENOTYPE; HUMANS; MALE; MIDDLE AGED; NUCLEAR PROTEINS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROMOTER REGIONS, GENETIC;

EID: 84871119502     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0051531     Document Type: Article

References (29)

1. Herman JG, Baylin SB, (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349: 2042-2054.
2. Toyota M, Issa JP, (1999) CpG island methylator phenotypes in aging and cancer. Semin Cancer Biol 9: 349-357.
3. Jones PA, Baylin SB, (2007) The epigenomics of cancer. Cell 128: 683-962.
4. Gardiner-Garden M, Frommer M, (1987) CpG islands in vertebrate genomes. J Mol Biol 196: 261-282.
5. Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, et al. (2009) The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 41: 178-186.
6. The International HapMap Consortium, (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449: 851-861.
7. Houlston RS, Webb E, Broderick P, Pittman AM, Di Bernardo MC, et al. (2008) Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nat Gen 40: 1426-1435.
8. Mrkonjic M, Roslin NM, Greenwood CM, Raptis S, Pollett A, et al. (2010) Specific variants in the MLH1 gene region may drive DNA methylation, loss of protein expression, and MSI-H colorectal cancer. PLoS One 5: e13314.
9. Boland CR, Goel A, (2010) Microsatellite instability in colorectal cancer. Gastroenterology 138: 2073-2087.
10. Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, et al. (1997) Methylation of the hMLH1 promoter correlates with a lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res 57: 808-811.
11. Raptis S, Mrkonjic M, Green RC, Pethe VV, Monga N, et al. (2007) MLH1-93G>A promoter polymorphism and the risk of microsatellite-unstable colorectal cancer. J Natl Cancer Inst 99: 463-474.
12. Perera S, Mrkonjic M, Rawson JB, Bapat B, (2011) Functional effects of the MLH1-93G>A polymorphism on MLH1/EPM2AIP1 promoter activity. Oncol Rep 25: 809-815.
13. Newcomb PA, Baron J, Cotterchio M, Gallinger S, Grove J, et al. (2007) Colon Cancer Family Registry: an international resource for studies of the genetic epidemiology of colon cancer. Cancer Epidemiol Biomarkers Prev 16: 2331-2342.
14. Zanke BW, Greenwood CM, Rangrej J, Kustra R, Tenesa A, et al. (2007) Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet 39: 989-994.
15. Deng G, Chen A, Hong J, Chae HS, Kim YS, (1999) Methylation of CpG in a small region of the hMLH1 promoter invariably correlates with the absence of gene expression. Cancer Res 59: 2029-2033.
16. Bird A, Taggart M, Frommer M, Miller OJ, Macleod D, (1985) A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell 40: 91-99.
17. Feber A, Wilson GA, Zhang L, Presneau N, Idowu B, et al. (2011) Comparative methylome analysis of benign and malignant peripheral nerve sheath tumors. Genome Res 21: 515-524.
18. Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, et al. (2012) Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci USA 109: 10522-10527.
19. Gibbs JR, van der Brug MP, Hernandez DG, Traynor BJ, Nalls MA, et al. (2010) Abundant quantitative trait Loci exist for DNA methylation and gene expression in human brain. PLoS Genet 6: e1000952.
20. Müller K, Heller H, Doerfler W, (2001) Foreign DNA integration. Genome-wide perturbations of methylation and transcription in the recipient genomes. J Biol Chem 276: 14271-14278.
21. Bell CG, Finer S, Lindgren CM, Wilson GA, Rakyan VK, et al. (2010) Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus. PLoS One 5: e14040.
22. Whiffin N, Broderick P, Lubbe SJ, Pittman AM, Penegar S, et al. (2011) MLH1-93G>A is a risk factor for MSI colorectal cancer. Carcinogenesis 32: 1157-1161.
23. Jiang Haiyan, Orr A, Guernsey DL, Robitaille J, Asselin G, et al. (2009) Application of homozygosity haplotype analysis to genetic mapping with high-density SNP genotype data. PLoS ONE 4: e5280.
24. Schumacher FR, Feigelson HS, Cox DG, Haiman CA, Albanes D, et al. (2007) A common 8q24 variant in prostate and breast cancer from a large nested case-control study. Cancer Res 67: 2951-2956.
25. Meyer KB, Maia AT, O'Reilly M, Ghoussaini M, Prathalingam R, et al. (2011) A functional variant at a prostate cancer predisposition locus at 8q24 is associated with PTVT1 expression. PLoS Genet 7: e1002165.
26. Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, et al. (2009) The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat Genet 41: 885-890.
27. Koestler DC, Marsit CJ, Christensen BC, Accomando W, Langevin SM, et al. (2012) Peripheral blood immune cell methylation profiles are associated with nonhematopoietic cancers. Cancer Epidemiol Biomarkers Prev 21: 1293-1302.
28. Arnold CR, Wolf J, Brunner S, Herndler-Brandstetter D, Grubeck-Loebenstein B, (2011) Gain and loss of T cell subsets in old age - age-related reshaping of the T cell repertoire. J Clin Immunol 31: 137-146.
29. Perez-Andres M, Paiva B, Nieto WG, Caraux A, Schmitz A, et al. (2010) Human Peripheral blood B-cell compartments: a crossroad in B-cell traffic. Cytometry B Clin Cytom 78: S47-S60.