title: Clinical significance of the FV:Q506 mutation in unselected oncology patients.
abstract: OBJECTIVE
  A common germline mutation in the factor V gene (FV:Q506) has been associated with hypercoagulability in families with heritable predisposition to thrombosis. We examined the prevalence and clinical significance of the FV:Q506 mutation in cancer patients.
  
  
  METHODS
  We performed a retrospective cohort study by examining 353 consecutive, unselected patients in a general hematology/oncology clinic. We ascertained risk factors, obtained the clinical clotting history, and determined the heterozygous or homozygous presence of the FV:Q506 allele for each patient.
  
  
  RESULTS
  We detected a germline mutation in 5.4% (19 of 353) of patients, of whom 18 were heterozygous and 1 was homozygous for the FV:Q506 mutant allele. In 17 of 18 heterozygous patients, there was no history of venous thrombosis or catheter-associated thrombosis. These asymptomatic patients included 13 patients who had been diagnosed with cancer or leukemia for a mean of 66.2 months (median 69) and had received a variety of local and systemic treatments. In contrast, 1 of 18 heterozygous and 1 of 1 homozygous patients had developed deep vein thrombosis that was associated, respectively, with either recurrent thrombotic events or a strong family history for pulmonary embolus.
  
  
  CONCLUSIONS
  Routine screening for the FV:Q506 mutation in cancer patients without a personal or family history for venous thrombosis is not helpful in guiding management. In contrast, an episode of venous thrombosis in a patient with a mutant germline FV:Q506 allele was associated with recurrent thrombotic events. These findings suggest that patients heterozygous for the FV:Q506 allele may require an independent "susceptibility" element to manifest a venous hypercoagulable state. In addition, only 2 of 25 clinic patients with a venous clot carried the FV:Q506 allele suggesting this genetic defect plays a minor role in the hypercoagulable state of cancer.
authors.affiliation: National Cancer Institute-Navy Oncology Branch, National Naval Medical Center, Bethesda, Maryland 20889, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Otterson
authors.forename: B P
authors.initials: BP
authors.lastname: Monahan
authors.forename: N
authors.initials: N
authors.lastname: Harold
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: J N
authors.initials: JN
authors.lastname: Frame
authors.forename: F J
authors.initials: FJ
authors.lastname: Kaye
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D005165:Factor V / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D011655:Pulmonary Embolism / Q000150:complications / Q000235:genetics; D012189:Retrospective Studies; D013924:Thrombophlebitis / Q000150:complications / Q000235:genetics
chemical_list: D005165:Factor V