title: Prognostic implications of loss of heterozygosity at 8p21 and 9p21 in head and neck squamous cell carcinoma.
abstract: Loss of heterozygosity (LOH) in chromosomal regions that harbor tumor suppressor genes from tumor tissue may lead to decreased survival time in cancer patients with squamous cell carcinoma of the head and neck (HNSCC). We studied 8 regions frequently lost in HNSCC in 150 patients having a primary diagnosis of HNSCC. Tumor and normal tissue DNA were genotyped for microsatellite repeat markers in 8 unlinked chromosomal regions. The association between LOH and death from HNSCC was investigated, weighted by number of informative markers per region and adjusted for age at diagnosis, self-reported race, tumor stage and current smoking status. LOH at 3 chromosomal regions were independently associated with reduced survival. A greater risk for cancer mortality was observed for LOH at chromosomal regions 3p24.3-p14.3 (p = 0.02), 8p21.3-p11.21 (p = 0.02) and 9p24.2-p21.2 (p = 0.03). In these regions, LOH at one or more markers was observed in 66.9%, 43.3% and 60.6% of patients, respectively. Survival times were significantly shorter for those with LOH at marker NEFL on 8p21.2 (relative risk = 6.15; p = 0.0002) and at D9S126 on 9p21.2 (relative risk = 5.96; p = 0.0003). Our results indicate that LOH at several chromosomal sites may offer additional independent prognostic information beyond traditional indicators such as tumor stage and age.
authors.affiliation: Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, MI 48202, USA. scoon1@hfhs.org
authors.forename: Steven W
authors.initials: SW
authors.lastname: Coon
authors.forename: Adnan T
authors.initials: AT
authors.lastname: Savera
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Zarbo
authors.forename: Michael S
authors.initials: MS
authors.lastname: Benninger
authors.forename: Gary A
authors.initials: GA
authors.lastname: Chase
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Rybicki
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Van Dyke
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004273:DNA, Neoplasm; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm; D005819:Genetic Markers