Influence of age on adenomatous polyposis coli and p53 mutation frequency in sporadic colorectal cancer-rarity of co-occurrence of mutations in APC, K-ras, and p53 genes

Virchows Arch. 2004 Nov;445(5):465-71. doi: 10.1007/s00428-004-1116-z. Epub 2004 Sep 24.

Abstract

Introduction: Previous studies have investigated the possibility that specific mutations may be related to specific clinicopathological features. However, most previous investigations included only an average age (40-80 years) group of sporadic colorectal cancers and, moreover, studied only a single gene in isolation. Therefore, the influence of age on these mutation frequencies remains unclear, despite age being considered a risk factor for genetic mutation.

Materials and methods: This study included 122 sporadic colorectal cancers from three different age groups and analyzed mutation frequencies of adenomatous polyposis coli (APC), K-ras, and p53 genes and microsatellite instability to determine their mutation frequencies and relationships with clinicopathological features.

Results: Significantly lower p53 mutation frequencies were observed among young (32 years old or younger) and old (86 years old or older) patient groups compared with an average age (39-85 years old) patient group (14.3% and 19.2% versus 51.5%, P<0.001). APC mutation frequency (11.8%) was significantly lower in highly aggressive (Dukes' stage D) tumors ( P=0.003) than in the other stage tumors (Dukes' stage A, B, and C). Additionally, simultaneous occurrence of all three genetic alterations in an individual tumor was rare (below 5%). Statistical analysis further confirmed that mutation number in Dukes' D tumors occurred less frequently than expected in other stage tumors ( P=0.008).

Conclusions: Genetic alterations of sporadic colorectal cancers have different relationships with age or tumor stage. Additionally, most sporadic colorectal tumors do not necessarily require following the widely accepted genetic model, because the three key genetic mutations, APC, K-ras, and p53, rarely occur simultaneously.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / etiology*
  • Adenomatous Polyposis Coli / genetics
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / genetics*
  • Female
  • Genes, APC
  • Genes, p53*
  • Genes, ras*
  • Humans
  • Male
  • Middle Aged
  • Mutation*