Skip Navigation


Carcinogenesis Advance Access originally published online on October 17, 2007
Carcinogenesis 2007 28(12):2575-2580; doi:10.1093/carcin/bgm229
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
28/12/2575    most recent
bgm229v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Mrkonjic, M.
Right arrow Articles by Bapat, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mrkonjic, M.
Right arrow Articles by Bapat, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

MSH2 –118T>C and MSH6 –159C>T promoter polymorphisms and the risk of colorectal cancer

Miralem Mrkonjic1,2,3, Stavroula Raptis1,2,3, Roger C. Green4, Neerav Monga5, Darshana Daftary5, Elizabeth Dicks6, H.Banfield Younghusband4, Patrick S. Parfrey7, Steven S. Gallinger2,8,9, John R. McLaughlin2,10,11, Julia A. Knight2,10,11 and Bharati Bapat1,2,3,*

1 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario M5T 3L9, Canada
2 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5T 3L9, Canada
3 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L5, Canada
4 Department of Genetics, Memorial University, St John's, Newfoundland A1B 3V6, Canada
5 Ontario Familial Colorectal Cancer Registry, Cancer Care Ontario, Toronto, Ontario M5G 2L7, Canada
6 Faculty of Medicine, Memorial University, St John's, Newfoundland A1B 3V6, Canada
7 Department of Clinical Epidemiology, Memorial University, St John's, Newfoundland A1B 3V6, Canada
8 Department of Surgery, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
9 Department of Surgery, University of Toronto, Toronto, Ontario M5G 1L5, Canada
10 Prosserman Centre for Health Research, Mount Sinai Hospital M5T 3L9, Toronto, Ontario, Canada
11 Department of Public Health Sciences, University of Toronto, Toronto, Ontario M5T 3M7, Canada

* To whom correspondence should be addressed. Tel: +416 586 4800 ext. 5175; Fax: +416 361 2655; Email: bapat{at}mshri.on.ca

The most important indicator of colorectal cancer (CRC) risk is the presence of family history of the disease. Inherited genetic changes, such as single nucleotide polymorphisms, in key candidate genes may contribute to CRC risk. We investigated whether promoter polymorphisms in DNA mismatch repair (MMR) genes MSH2 and MSH6 are associated with the risk of CRC. We genotyped 929 CRC patients and 1098 control subjects from Ontario, and 467 patients and 344 controls from Newfoundland and Labrador, for two promoter polymorphisms in the MMR genes MSH2 and MSH6 using the fluorogenic 5' nuclease assay. We used unconditional logistic regression to evaluate the association between each polymorphism and CRC after adjusting for age and sex. The associations between polymorphisms and tumor clinicopathological features were evaluated with a Pearson's chi-squared test or Fisher's exact test. All statistical tests were two sided. We observed strong associations between the MSH2 –118T>C polymorphism and family history of CRC based on the Amsterdam criteria I (P = 0.005) and Amsterdam criteria I and II (P = 0.036) among cases from Ontario. This association was especially evident among female CRC patients in Ontario (for Amsterdam criteria I, and I and II combined, P = 0.003 and P = 0.0001, respectively). The MSH2 –118T>C polymorphism was associated with strong family history of CRC in Ontario patients.

Abbreviations: CRC, colorectal cancer; HNPCC, hereditary non-polyposis colorectal cancer; MMR, mismatch repair; MSI, microsatellite instability; MSI-H, high-frequency MSI; PCR, polymerase chain reaction; SNP, single nucleotide polymorphism

Received July 19, 2007; revised August 31, 2007; accepted September 28, 2007.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.