Aberrant Methylation of p16INK4a in Anatomic and Gender-specific Subtypes of Sporadic Colorectal Cancer

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 p16 INK4a tumor suppressor gene w...

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Bibliographic Details
Published in:Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 1999-06, Vol.8 (6), p.501-506
Main Authors: WIENCKE, J. K, ZHENG, S, LAFUENTE, A, LAFUENTE, M. J, GRUDZEN, C, WRENSCH, M. R, MIIKE, R, BALLESTA, A, TRIAS, M
Format: Article
Language:English
Subjects:
Aged
Biological and medical sciences
Colorectal Neoplasms - classification
Colorectal Neoplasms - epidemiology
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
DNA Methylation
DNA, Neoplasm - analysis
DNA, Neoplasm - genetics
Female
Gastroenterology. Liver. Pancreas. Abdomen
Genes, p16 - genetics
Humans
Logistic Models
Male
Medical sciences
Middle Aged
Neoplasm Staging
Polymerase Chain Reaction
Sex Distribution
Spain - epidemiology
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
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Summary: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 p16 INK4a tumor suppressor gene was associated with anatomical location, gender, or other clinicopathological characteristics. Overall, 18.3% of the tumors had detectable p16 INK4a 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 p16 INK4a compared with distal tumors. In addition, female patients were 8.8 times more likely than males to have methylation-positive cancers, and p16 INK4a methylation was also associated with poorly differentiated tumors. The localization of tumors with p16 INK4a 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.
ISSN:1055-9965
1538-7755