@article{Chao06cebp,
   author = {D. L. Chao and C. C. Maley and X. Wu and D. C. Farrow and P. C. Galipeau and C. A. Sanchez and T. G. Paulson and P. S. Rabinovitch and B. J. Reid and M. R. Spitz and T. L. Vaughan },
   editor = {2006/10/13 09:00},
   title = {Mutagen Sensitivity and Neoplastic Progression in Patients with {Barrett's} Esophagus: A Prospective Analysis},
   journal = {Cancer Epidemiol Biomarkers Prev},
   volume = {15},
   number = {10},
   pages = {1935-40},
   address = {Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, C1-157, Seattle, WA 98109. dchao@fhcrc.org.},
   month = {Oct},
   year = {2006},
   abstract = {BACKGROUND: Defects in DNA damage recognition and repair have been
associated with a wide variety of cancers. We conducted a prospective
study to determine whether mutagen sensitivity, as determined by an in
vitro assay, was associated with the future development of cancer in
patients with Barrett's esophagus, which is associated with increased risk
of progression to esophageal adenocarcinoma. METHODS: We measured
sensitivity to bleomycin in peripheral blood lymphocytes in a cohort of
220 patients with Barrett's esophagus. We followed these patients for
1,230 person-years (range, 3 months to 10.1 years; median, 6.4 years),
using development of cancer and aneuploidy as end points. A subset of
these patients was evaluated for inactivation of tumor-suppressor genes
CDKN2A/p16 and TP53 [by mutation and loss of heterozygosity (LOH)] in
their Barrett's segments at the time of, or before, the bleomycin test,
and the patients were stratified by CDKN2A/p16 and TP53 status in an
analysis of mutagen sensitivity and progression. RESULTS:
Bleomycin-sensitive patients were found to be at significantly greater
risk of developing aneuploidy (adjusted hazard ratio, 3.71; 95\% confidence
interval, 1.44-9.53) and nonsignificantly greater risk of cancer (adjusted
hazard ratio, 1.63; 95\% confidence interval, 0.71-3.75). Among patients
with detectable LOH at the TP53 locus (on chromosome 17p), increasing
bleomycin sensitivity was associated with increased risk of developing
cancer (P(trend) \< 0.001) and aneuploidy (P(trend) = 0.005). CONCLUSIONS:
This study supports the hypothesis that sensitivity to mutagens increases
the risk of neoplastic progression in persons with Barrett's esophagus,
particularly those with 17p LOH including TP53. (Cancer Epidemiol
Biomarkers Prev 2006;15(10):1935-40).}
}