Confirmation of linkage to and localization of familial colon cancer risk haplotype on chromosome 9q22

Courtney Gray-McGuire, Kishore Guda, Indra Adrianto, Chee Paul Lin, Leanna Natale, John D. Potter, Polly Newcomb, Elizabeth M. Poole, Cornelia M. Ulrich, Noralane Lindor, Ellen L. Goode, Brooke L. Fridley, Robert Jenkins, Loic Le Marchand, Graham Casey, Robert Haile, John Hopper, Mark Jenkins, Joanne Young, Daniel BuchananSteve Gallinger, Mark Adams, Susan Lewis, Joseph Willis, Robert Elston, Sanford D. Markowitz, Georgia L. Wiesner

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Genetic risk factors are important contributors to the development of colorectal cancer. Following the definition of a linkage signal at 9q22-31, we fine mapped this region in an independent collection of colon cancer families. We used a custom array of single-nucleotide polymorphisms (SNP) densely spaced across the candidate region, performing both single-SNP and moving-window association analyses to identify a colon neoplasia risk haplotype. Through this approach, we isolated the association effect to a five-SNP haplotype centered at 98.15 Mb on chromosome 9q. This haplotype is in strong linkage disequilibrium with the haplotype block containing HABP4 and may be a surrogate for the effect of this CD30 Ki-1 antigen. It is also in close proximity to GALNT12, also recently shown to be altered in colon tumors. We used a predictive modeling algorithm to show the contribution of this risk haplotype and surrounding candidate genes in distinguishing between colon cancer cases and healthy controls. The ability to replicate this finding, the strength of the haplotype association (odds ratio, 3.68), and the accuracy of our prediction model (∼60%) all strongly support the presence of a locus for familial colon cancer on chromosome 9q.

Original languageEnglish (US)
Pages (from-to)5409-5418
Number of pages10
JournalCancer research
Volume70
Issue number13
DOIs
StatePublished - Jul 1 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Gray-McGuire, C., Guda, K., Adrianto, I., Lin, C. P., Natale, L., Potter, J. D., Newcomb, P., Poole, E. M., Ulrich, C. M., Lindor, N., Goode, E. L., Fridley, B. L., Jenkins, R., Le Marchand, L., Casey, G., Haile, R., Hopper, J., Jenkins, M., Young, J., ... Wiesner, G. L. (2010). Confirmation of linkage to and localization of familial colon cancer risk haplotype on chromosome 9q22. Cancer research, 70(13), 5409-5418. https://doi.org/10.1158/0008-5472.CAN-10-0188