Abstract
Colorectal cancer (CRC) occurring in the proximal colon and among women may represent a distinct subtype of the disease. In the present study of 120 sporadic CRCs, we used methylation-specific PCR to test whether methylation of the CpG island in the 5′ region of the p16INK4a tumor suppressor gene was associated with anatomical location, gender, or other clinicopathological characteristics. Overall, 18.3% of the tumors had detectable p16INK4a methylation. A marked preponderance of methylated tumors occurred within the proximal colon; cancers occurring proximal to the sigmoid colon were 13.1 times more likely to contain methylated p16INK4a compared with distal tumors. In addition, female patients were 8.8 times more likely than males to have methylation-positive cancers, and p16INK4a methylation was also associated with poorly differentiated tumors. The localization of tumors with p16INK4a methylation within the proximal colon and among female patients specifically adds to a growing database of molecular alterations that define important subtypes of sporadic CRC. The potentially reversible nature of CpG methylation may provide novel therapeutic opportunities for this increasing subtype of the disease, which, due to anatomical location, presents a great challenge for early detection.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 Supported by the Foundation Marato (A. L., M. J. L.) and the National Institutes of Environmental Health Sciences NIH Grant P42-ESO4705 with funds provided by the Environmental Protection Agency (J. K. W., S. Z., C. G.).
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↵2 To whom requests for reprints should be addressed, at Laboratory for Molecular Epidemiology, Department of Epidemiology and Biostatistics, University of California San Francisco, 500 Parnassus Avenue, MU-W 420, San Francisco, CA 94143-0560.
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↵3 The abbreviations used are: CRC, colorectal cancer; MSPCR, methylation-specific PCR; APC, adenomatous polyposis coli; HNPCC, hereditary nonpolyposis colorectal cancer; OR, odds ratio.
- Accepted April 7, 1999.
- Received December 4, 1998.
- Revision received March 15, 1999.
Volume 8, Issue 6
