The Laryngoscope
Lippincott Williams & Wilkins, Inc.
© 2004 The American Laryngological,
Rhinological and Otological Society, Inc.
Microsatellite Alterations in African
Americans with Head and Neck Cancer
George H. Yoo, MD; Nghia X. Nguyen, MD; Wei Du, PhD; Ann G. Schwartz, PhD; Susan Land, PhD;
Ho-Sheng Lin, MD; Danny Kewson, MD; Leslie L. Murphy; Dave Cilluffo; John F. Ensley, MD;
Michael A. Tainsky, PhD
Objective: To determine the genetic differences
between African Americans (AA) and Non-African
Americans (NAA) with head and neck squamous cell
carcinoma (HNSCC). Methods: DNA was obtained
from tumor tissues and peripheral blood from 18 AA
and 19 NAA patients with HNSCC. Microsatellite
analysis using a fluorescent technique was performed
on chromosomal arms 1p, 3p, 4q, 9p, 13q, and 17p.
Statistical analyses were performed on the molecular
and clinical outcome data. Results: Based on the Sur-
veillance, Epidemiologic, and End Result (SEER) data
from southeast Michigan, the incidence rate of
HNSCC in AA has been higher than for NAA, and the
overall 5-year relative survival rate is lower for AA
than NAA (36.2% vs. 47.6%). In this study, we found
that the rate of loss of heterozygosity of chromosomal
arms 1p, 3p, 4q, 9p, 13q, and 17p ranged from 68.8% to
83.3% for HNSCC in AA and from 66.7% to 90.0% in
NAA. The difference in the rates of microsatellite
alterations in chromosomal arms 3p, 4q, and 9p
between AA and NAA were between 12.5% and 20%
and were not statistically significant. Conclusion:
The incidence and clinical outcomes for AA with
HNSCC are different from that of NAA in south-
east Michigan. In our group of patients with
HNSCC, differences in rates of microsatellite al-
terations and survival were found between AA
and NAA; however, these differences were not sta-
tistically significant. We conclude that genetic
difference, as determined by the rates of micro-
satellite alterations, is not predictive of outcome
difference between AA and NAA HNSCC patients.
Key Words: Microsatellite analysis, head and neck
cancer, loss of heterozygosity.
Laryngoscope, 114:1619 –1624, 2004
INTRODUCTION
African Americans (AA) have previously been shown
to have a higher incidence of head and neck squamous cell
carcinoma (HNSCC) than that of non-African Americans
(NAA) and lower survival rates.
1–3
This discrepancy may
be partially attributed to socioeconomic factors, such as
delay in diagnosis, poor compliance or follow-up, and other
epidemiologic factors such as higher level of tobacco or
alcohol exposure;
4
however, genetic factors may also con-
tribute to the discrepancy.
5–7
Racial differences in genetic
alterations in AA as opposed to NAA have been docu-
mented for oral and breast cancer. For example, novel p53
mutations in oral and breast cancer in the AA population
have been reported.
5,6
In addition, genetic alterations,
such as p53 mutations, in AA with breast cancer have
been associated with a significantly worse prognosis.
7
Genetic alterations in various chromosomal arms,
such as loss of heterozygosity (LOH) at 3p, 8p, 11q, 14q,
17p, and 18q
8–12
and p53 mutations
10
have been shown to
predict poor survival and recurrence in HNSCC. Mutagen
sensitive individuals, as determined by the bleomycin-
induced chromatid breaks assay, have been shown to have
more advanced disease and a higher likelihood of chromo-
somal loss associated with alcohol and tobacco use.
13
Moreover, risk estimates for mutagen sensitivity and lung
cancer have been reported to be higher in AA than in the
white population.
14
These data suggest that there are
genetic differences in different subsets of patients with
HNSCC, as well as other cancers, which are associated with
more advanced disease and poor prognosis. Therefore, it is
be important to determine whether there are genetic differ-
ences in AA with HNSCC as compared with NAA that might
account for the racial disparity in survival.
Microsatellite markers are short tandem repeats that
are dispersed throughout the genome.
15
Microsatellite al-
terations are thought to be an integral part of neoplastic
progression and have been found in a variety of cancers
including lung, colorectal, cervical, brain, breast, and
HNSCC.
16 –21
The use of fluorescent microsatellite analy-
From the Department of Otolaryngology—Head and Neck Surgery
(G.H.Y., N.X.N., H.S.L., D.K., J.F.E.), Wayne State University, Detroit, MI; the
Department of Medicine, Division of Hematology/Oncology (A.S., W.D.,
J.F.E.), Wayne State University and Karmanos Cancer Institute, Detroit,
MI; the Molecular Biology and Human Genetics Program (S.L.)., Wayne
State University, Applied Genomic Technology Center, Michigan Center
for Genomic Technology, and Karmanos Cancer Institute, Detroit, MI;
Compuware Corporation (L.L.M., D.C.), Detroit, MI; and the Molecular Bi-
ology and Human Genetics Program (M.A.T.), Wayne State University and
Karmanos Cancer Institute, Detroit, MI, U.S.A.
Editor’s Note: This Manuscript was accepted for publication Febru-
ary 6, 2004.
Send Correspondence to Dr. George H. Yoo, Department of Otolar-
yngology—Head and Neck Surgery, Wayne State University, 5E Univer-
sity Health Center, 540 E. Canfield Avenue, Detroit, MI 48201, U.S.A.
E-mail: gyoo@med.wayne.edu
Laryngoscope 114: September 2004 Yoo et al.: Gene Alterations in Head and Neck Cancer
1619