Total number of genome alterations in sporadic gastrointestinal cancer inferred from pooled analyses in the literature

Background/aims: A previous study based on the age distribution of human cancers has demonstrated that about 6 or 7 mutations are required for gastrointestinal cancer to develop. This study aims to provide further insight into this issue through a systematic review of current knowledge found in the literature.

Methods: The PubMed database was searched for entries up to December 2007 for eligible studies pertaining to chromosome aberrations and gene mutations in sporadic esophageal, gastric, colorectal and pancreatic cancers.

Results: Of 29,308 potentially eligible titles, 302 representative reports were included in the pooled analysis. Frequently reported genome alterations were: the +3q27 and +8q24 mutations of TP53 for esophageal cancer; +20q13 for gastric cancer; -18q22 and +20q12-q13 mutations of APC, TP53 and KRAS for colorectal cancer, and the -18q22 mutation of KRAS and TP53 for pancreatic cancer. Based on the frequencies of major events, which represents the expected value of the occurrence, the total number of genome alterations was estimated at 8.99 for esophageal, 4.18 for gastric, 7.36 for colorectal and 5.74 for pancreatic cancer.

Conclusion: The genetic changes summarized here, predominantly chromosome alterations, constitute a major factor in the development of these cancers, so that it may be advisable on focus molecular strategies for diagnosis and treatment of these events.