Increase in the frequency of K-ras codon 12 point mutation in colorectal carcinoma in elderly males in Japan: the 1990s compared with the 1960s.

The incidence of colorectal carcinomas has been increasing over the last 50 years in Japan. In order to determine whether adenoma-carcinoma sequence (ACS) or de novo cancer development, generally considered to be two separate genetic pathways, might be responsible, K-ras codon 12 mutations, good markers for ACS, were examined in 59 and 84 cases of advanced colorectal cancer surgically resected in Cancer Institute Hospital of the Japanese Foundation for Cancer Research in 1960-1969 and in 1990-1999, respectively. There was no significant difference of K-ras codon 12 mutation between the 25.4% (15/59) in the 1960s and 36.9% (31/84) in the 1990s (P = 0.148), and the reference of distal colon cancer also showed no significant difference between 24.4% (11/45) and 36.4% (20/55). Yet elderly males showed a significant difference: 27.3% (6/22) in the 1960s and 59.3% (16/27) in the 1990s. The references of males, elderly patients (over 75 years old) and distal colon cancer in the 1990s were significantly more likely to demonstrate mutations than their counterparts in the 1960s. There was no variation with the tumor location. The results suggest that the ACS pathway might have primarily contributed to the increased incidence of colorectal cancer in elderly males in Japan.