Linkage studies have implicated chromosome 17q21-22 as a possible
location of a prostate-cancer susceptibility gene.
METHODS
We screened more than 200 genes in the 17q21-22 region by sequencing germline DNA from 94 unrelated patients with prostate cancer from families selected for linkage to the candidate region. We tested family members, additional case subjects, and control subjects to characterize the frequency of the identified mutations.
RESULTS
Probands from four families were discovered to have a rare but recurrent mutation (G84E) in HOXB13 (rs138213197), a GSK J4 supplier homeobox transcription factor gene that is important in prostate development. All 18 men with prostate cancer and available DNA in these four families carried the mutation. The carrier rate of the G84E mutation was increased by
a factor of approximately 20 in 5083 unrelated subjects of European descent who had prostate cancer, with the mutation found in 72 subjects (1.4%), as compared with 1 in 1401 control subjects (0.1%) (P = 8.5×10(-7)). The mutation was significantly more common in men with early-onset, familial prostate cancer (3.1%) than in those with late-onset, nonfamilial prostate cancer (0.6%) (P = 2.0×10(-6)).
CONCLUSIONS
The novel HOXB13 G84E variant is associated with a significantly increased risk of hereditary prostate cancer. Although the variant accounts for a small fraction of all prostate cancers, this finding has implications for prostate-cancer risk assessment and may provide new mechanistic insights into this this website common cancer. (Funded by the National Institutes of Health and others.)”
“Objective:
Intrathoracic esophageal anastomotic leaks and perforations are very morbid and challenging problems. Esophageal stents are increasingly playing an integral role in the management of these patients. Our objective AZD5582 chemical structure was to report our experience with esophageal stent placement for anastomotic leaks and perforations and to provide a treatment algorithm.
Methods: We performed a review of patients with stent placement for esophagogastric anastomotic leaks or esophageal perforation from March 2005 to August 2009. A prospective database was used to collect data. Success was defined as endoscopic defect closure, negative esophagram, and resumption of oral intake. Failure was defined as no change in leak size or clinical signs of ongoing infection. We collected and analyzed patient demographics, diagnosis, clinical history, and poststent outcomes using descriptive statistics.
Results: Thirty-seven patients underwent esophageal stent placement for anastomotic leaks (n = 22) and perforations (n = 15). The median time from original procedure to diagnosis of leak or perforation was 6 days (0-420 days). Nineteen patients (51%) had 21 associated procedures for source control. We placed 94 stents (mean – 2.