Incidence of DNA replication errors in patients with multiple primary cancers.
OBJECTIVE
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.


METHODS
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.


RESULTS
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 frequency remained in both the multiple primary group (P < 0.005) and multiple colorectal and colorectal/uterine subgroups (P < 0.001).


CONCLUSIONS
Results suggest that genetic instability plays an important role in development of multiple primary cancers, particularly from certain cancer subsets. Testing for replication errors may be an appropriate way of identifying individuals at risk of multiple primary cancers.
Brown
S R
SR
Centre for Digestive Diseases, Leeds General Infirmary, United Kingdom.
Finan
P J
PJ
Hall
N R
NR
Bishop
D T
DT
D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm