Incidence of DNA replication errors in patients with multiple primary cancers

Diseases of the Colon and Rectum
S R BrownD T Bishop

Abstract

Multiple primary cancers are a feature of hereditary nonpolyposis colorectal cancer in which defects in DNA repair mechanisms result in accumulation of replication errors within tumor DNA. We assessed replication error incidence in multiple primary cancer patients who may have similar genetic defects. DNA was obtained from 69 patients from the Yorkshire region who had developed colorectal cancer and one other primary tumor from the hereditary nonpolyposis colorectal cancer tumor spectrum (28 colorectal, 12 stomach, 15 ovary, and 14 uterus). DNA was also obtained from 86 sporadic, single primary cancer patients attending a colorectal cancer clinic. Replication error status was assessed at five microsatellite loci using fluorescent polymerase chain reaction and computer-assisted analysis. The replication error phenotype was observed in 7 of 86 (8 percent) of the sporadic single primary patients. This compared with 23 of 69 (33 percent) of the multiple primary group (P < 0.001). Replication error was also observed more frequently in each subgroup. Even excluding patients from families meeting the Amsterdam criteria (likely to be hereditary nonpolyposis colorectal cancer and have the replication error phenotype), this increased fre...Continue Reading

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