Grant Details
Grant Number: |
5R01CA090731-05 Interpret this number |
Primary Investigator: |
Olshan, Andrew |
Organization: |
Univ Of North Carolina Chapel Hill |
Project Title: |
Gene Environment Interaction in Head and Neck Cancer |
Fiscal Year: |
2005 |
Abstract
DESCRIPTION: The major goal of the proposed study is to comprehensively
evaluate the role of genetic susceptibility in the etiology of squamous cell
carcinoma of the head and neck (SCCHN; including oral cavity, pharynx, and
larynx). SCCHN provides an ideal model for the investigation of
gene-environment interaction in cancer given its strong and highly prevalent
risk factors, tobacco and alcohol. Polymorphisms in genes representing
metabolism (activation and detoxification) of carcinogens, mediators of
oxidative stress, and DNA repair may help to clarify dose-response
relationships needed for risk assessment, elucidate low dose exposure effects,
pinpoint specific carcinogens that act as part of complex mixtures, and to
identify susceptible subgroups of individuals most likely to benefit from
interventions to reduce exposure.
The proposed North Carolina population-based case-control study including 1,700
cases and 1,700 controls will have the ability to more precisely define the
nature of the gene-environment interactions related to the risk of SCCHN. This
will be the largest study of head and neck cancer ever conducted in the United
States. North Carolina is an excellent setting to conduct such a study given
the large biracial population, relatively high prevalence of tobacco use, and
the research team's experience with conducting population-based molecular
epidemiologic studies of cancer. The previous gene-environment studies have
yielded generally inconsistent results with respect to several metabolizing
enzyme polymorphisms. These studies have been limited by their relatively small
size (typically fewer than 200 cases), hospital-based design and examination of
a small number of enzymes. The size and population-based design should allow us
to more confidently confirm or reject associations raised in previous studies.
Finally, the study size will permit us to consider selected gene-gene exposure
interactions and examine important subgroups defined by age, gender, race, and
tumor site. The systematic collection of tumor blocks will also facilitate
future studies of "downstream" somatic alterations of tumor suppressor genes
and oncogenes. The proposed study should contribute knowledge on
gene-environment interactions for cancer of the head and neck, but also for
other tobacco- and alcohol-related cancers and possibly cancers of unknown
etiology.
Publications
Partly linear single-index cure models with a nonparametric incidence link function.
Authors: Lee C.Y.
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, Bandyopadhyay D.
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EPub date: 2024-02-23 00:00:00.0.
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, Ness A.R.
, Liu G.
, Lacko M.
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, Abedi-Ardekani B.
, Beachler D.C.
, Conway D.I.
, Olshan A.F.
, Wunsch-Filho V.
, Toporcov T.N.
, Ahrens W.
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, Muscat J.
, Chen C.
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