© 2004 by Oxford University Press
© 2004 Oxford University Press
BRIEF COMMUNICATION |
Association Between Biallelic and Monoallelic Germline MYH Gene Mutations and Colorectal Cancer Risk
Affiliations of authors: Samuel Lunenfeld Research Institute (MEC, SPC, NDN, MM, JK, RG, SG) and Department of Surgery (RG, SG), Mount Sinai Hospital, Toronto, ON, Canada; Ontario Familial Colorectal Cancer Registry, Cancer Care Ontario, Toronto (MM, TS, MA, MC, JK, SG); Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (MR)
Correspondence to: Steven Gallinger, MD, MSc, FRCS, Rm. 1225, Mount Sinai Hospital, 600 University Ave., Toronto, ON, Canada M5G 1X5 (e-mail: sgallinger{at}mtsinai.on.ca)
The MutY human homologue (MYH) gene encodes a member of the base excision repair pathway that is involved in repairing oxidative damage to DNA. Two germline MYH gene mutations that result in Myh proteins containing amino acid substitutions Y165C and G382D (hereafter called the Y165C and G382D mutations) are associated with adenomatous poly-posis and colorectal cancer among patients from several European poly-posis registries. We used a population-based series of 1238 colorectal cancer patients and 1255 healthy control subjects from Ontario, Canada, to examine the risk of colorectal cancer among biallelic and monoallelic germline MYH Y165C and G382D mutation carriers. The entire MYH gene coding region was screened in all MYH Y165C and G382D mutation carriers. Compared with noncarriers, biallelic and monoallelic germline MYH gene mutation carriers had an increased risk of colorectal cancer and were more likely to have first-or second-degree relatives with colorectal cancer (relative risk = 1.54, 95% confidence interval = 1.10 to 2.16). The increased risk of colorectal cancer in biallelic and monoallelic MYH gene mutation carriers was not consistently associated with the development of multiple adenomatous polyps. Loss of heterozygosity in at least one of four loci in MYH was detected in eight (47%) of 17 colorectal tumors from monoallelic MYH gene mutation carriers but in only two (20%) of 10 colorectal tumors from biallelic MYH gene mutation carriers. These two MYH gene mutations may account for a substantial fraction of hereditary colorectal cancer.
CiteULike 
Connotea 
Del.icio.us What's this?
Correspondence about this Article
- Re: Association Between Biallelic and Monoallelic Germline MYH Gene Mutations and Colorectal Cancer Risk
- Albert Tenesa, Susan M. Farrington, and Malcolm G. Dunlop
J Natl Cancer Inst 2005 97: 320-321.[Extract] [Full Text] [PDF]
- RESPONSE: Re: Association Between Biallelic and Monoallelic Germline MYH Gene Mutations and Colorectal Cancer Risk
- Sean P. Cleary, Marina E. Croitoru, Robert Gryfe, Michael Manno, Michelle Cotterchio, Julia Knight, and Steven Gallinger
J Natl Cancer Inst 2005 97: 321-322.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
|
|
 |
|
  H F A Vasen, G Moslein, A Alonso, S Aretz, I Bernstein, L Bertario, I Blanco, S Bulow, J Burn, G Capella, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP) Gut, May 1, 2008; 57(5): 704 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. van Puijenbroek, M. Nielsen, C. M.J. Tops, H. Halfwerk, H. F.A. Vasen, M. M. Weiss, T. van Wezel, F. J. Hes, and H. Morreau Identification of Patients with (Atypical) MUTYH-Associated Polyposis by KRAS2 c.34G > T Prescreening Followed by MUTYH Hotspot Analysis in Formalin-Fixed Paraffin-Embedded Tissue Clin. Cancer Res., January 1, 2008; 14(1): 139 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mrkonjic, S. Raptis, R. C. Green, N. Monga, D. Daftary, E. Dicks, H.B. Younghusband, P. S. Parfrey, S. S. Gallinger, J. R. McLaughlin, et al. MSH2 118T>C and MSH6 159C>T promoter polymorphisms and the risk of colorectal cancer Carcinogenesis, December 1, 2007; 28(12): 2575 - 2580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Young, M. Jenkins, S. Parry, B. Young, D. Nancarrow, D. English, G. Giles, and J. Jass Serrated pathway colorectal cancer in the population: genetic consideration Gut, October 1, 2007; 56(10): 1453 - 1459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Raptis, M. Mrkonjic, R. C. Green, V. V. Pethe, N. Monga, Y. M. Chan, D. Daftary, E. Dicks, B. H. Younghusband, P. S. Parfrey, et al. MLH1 -93G>A Promoter Polymorphism and the Risk of Microsatellite-Unstable Colorectal Cancer J Natl Cancer Inst, March 21, 2007; 99(6): 463 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Peterlongo, N. Mitra, A. S. d. Abajo, M. d. l. Hoya, C. Bassi, L. Bertario, P. Radice, E. Glogowski, K. Nafa, T. Caldes, et al. Increased frequency of disease-causing MYH mutations in colon cancer families Carcinogenesis, November 1, 2006; 27(11): 2243 - 2249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Offit, K. Kohut, B. Clagett, E. A. Wadsworth, K. J. Lafaro, S. Cummings, M. White, M. Sagi, D. Bernstein, and J. G. Davis Cancer Genetic Testing and Assisted Reproduction J. Clin. Oncol., October 10, 2006; 24(29): 4775 - 4782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Barnetson, A. Tenesa, S. M. Farrington, I. D. Nicholl, R. Cetnarskyj, M. E. Porteous, H. Campbell, and M. G. Dunlop Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. N. Engl. J. Med., June 29, 2006; 354(26): 2751 - 2763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Sokhansanj and D. M. Wilson III Estimating the effect of human base excision repair protein variants on the repair of oxidative DNA base damage. Cancer Epidemiol. Biomarkers Prev., May 1, 2006; 15(5): 1000 - 1008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Gorgens, S. Kruger, E. Kuhlisch, C. Pagenstecher, R. Hohl, H. K. Schackert, and A. Muller Microsatellite Stable Colorectal Cancers in Clinically Suspected Hereditary Nonpolyposis Colorectal Cancer Patients without Vertical Transmission of Disease Are Unlikely to Be Caused by Biallelic Germline Mutations in MYH J. Mol. Diagn., May 1, 2006; 8(2): 178 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Piccioli, M. Serra, V. Gismondi, S. Pedemonte, F. Loiacono, S. Lastraioli, L. Bertario, M. De Angioletti, L. Varesco, and R. Notaro Multiplex Tetra-Primer Amplification Refractory Mutation System PCR to Detect 6 Common Germline Mutations of the MUTYH Gene Associated with Polyposis and Colorectal Cancer Clin. Chem., April 1, 2006; 52(4): 739 - 743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Jenkins, M. E. Croitoru, N. Monga, S. P. Cleary, M. Cotterchio, J. L. Hopper, and S. Gallinger Risk of Colorectal Cancer in Monoallelic and Biallelic Carriers of MYH Mutations: A Population-Based Case-Family Study. Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 312 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Woods, A. J. Hyde, F. K. Curtis, S. Stuckless, J. S. Green, A. F. Pollett, J. D. Robb, R. C. Green, M. E. Croitoru, A. Careen, et al. High Frequency of Hereditary Colorectal Cancer in Newfoundland Likely Involves Novel Susceptibility Genes Clin. Cancer Res., October 1, 2005; 11(19): 6853 - 6861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Nielsen, P F Franken, T H C M Reinards, M M Weiss, A Wagner, H van der Klift, S Kloosterman, J J Houwing-Duistermaat, C M Aalfs, M G E M Ausems, et al. Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP) J. Med. Genet., September 1, 2005; 42(9): e54 - e54. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Cleary, M. E. Croitoru, R. Gryfe, M. Manno, M. Cotterchio, J. Knight, and S. Gallinger RESPONSE: Re: Association Between Biallelic and Monoallelic Germline MYH Gene Mutations and Colorectal Cancer Risk J Natl Cancer Inst, February 16, 2005; 97(4): 321 - 322. [Full Text] [PDF]
|
|
|
|
|
|
A. Tenesa, S. M. Farrington, and M. G. Dunlop Re: Association Between Biallelic and Monoallelic Germline MYH Gene Mutations and Colorectal Cancer Risk J Natl Cancer Inst, February 16, 2005; 97(4): 320 - 321. [Full Text] [PDF]
|
|