Clinical implications of @entity6912 *28 genotype testing in @entity14 XXXX .

@entity1 @entity6912 @entity137 @entity2600 @entity294 @entity391 @entity1398 @entity14 @entity3 @entity204 @entity221
BACKGROUND: Metastatic @entity14 is frequently treated with @entity2600 , a topoisomerase-I inhibitor. The @entity6912 gene encodes for an enzyme that metabolizes @entity2600 , and its genetic variants were shown to be associated with increased @entity137 . We evaluated clinical outcomes associated with the @entity6912 *28 variant. METHODS: The study included 329 @entity14 @entity1 from the Israeli population-based Molecular Epidemiology of @entity14 who were treated with a chemotherapy regimen that included @entity2600 . @entity1 with @entity3 or disease recurrence were followed up for a median period of 2 years after occurrence of the event. Study end points were appearance of grade 3-4 hematological and gastroenterological @entity137 , hospitalization due to toxic events (mostly @entity1398 , @entity221 , @entity294 , or @entity391 ), length of hospitalization, and overall survival. @entity6912 *28 was genotyped from peripheral blood DNA by fragment analysis and reported as number of TATA sequence repeats in the promoter of the gene. RESULTS: The 7/7 variant of @entity6912 *28 was detected in 11.9% of the 329 @entity1 . Grade 3-4 hematological @entity137 was significantly higher in 7/7 carriers compared with 6/7 and 6/6 carriers (48.0%,10.2%, and 7.7% respectively; P < .001), as was the risk of @entity137 -related hospitalization (45.8%, 25.3%, and 14.4% respectively; P = .001). Both short-term @entity204 within 2 months of treatment start (12.8%, 5.2%, and 2.9%, respectively) and median overall survival (1.6, 2.0, and 2.4 years, respectively; P = .01) were significantly worse in the 7/7 carriers. The age/stage-adjusted hazard ratio for @entity1 with the 7/7 genotype compared with 6/6 was 1.7 (95% confidence interval, 1.1-2.3). CONCLUSIONS: The @entity6912 *28 7/7 genotype is strongly associated with severe hematological @entity137 and higher hospitalization rate and predicts lower survival of @entity14 in users of @entity2600 .
