Aberrant methylation of p16(INK4a) 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 s poradic 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 clinicopathologic al characteristics. Overall, 18.3% of the tumors had detectable p16(INK4a) methylation. A marked preponderance of methylated tumors occurred within th e proximal colon; cancers occurring proximal to the sigmoid colon were 13.1 times more likely to contain methylated p16(INK4a) compared with distal tu mors. In addition, female patients were 8.8 times more likely than males to have methylation-positive cancers, and p16(INK4a) methylation was also ass ociated 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 defin e important subtypes of sporadic CRC, The potentially reversible nature of CpG methylation may provide novel therapeutic opportunities for this increa sing subtype of the disease, which, due to anatomical location, presents a great challenge for early detection.