Grant Details
Grant Number: |
1R01CA087895-01A1 Interpret this number |
Primary Investigator: |
Schwartz, Ann |
Organization: |
Wayne State University |
Project Title: |
Adenocarinoma of the Lung in Women |
Fiscal Year: |
2001 |
Abstract
DESCRIPTION: In 1998, 80,000 women in the US were diagnosed with lung cancer
and incidence rates, particularly of adenocarcinoma, continue to increase among
women. Many pieces of evidence suggest that there are gender differences in
susceptibility to tobacco carcinogens. Several studies have shown that DNA
adducts, p53 mutations, CYP1A1 expression in the lung, and GSTM1 null genotypes
are more frequent in females than in males. Reasons for differential
susceptibility by gender might be explained by variations in metabolic enzyme
functioning or hormonal differences. Some of the same enzymes involved in the
metabolism of carcinogens in tobacco smoke are involved in the metabolism of
estrogen.
The goals of the proposed study are two-fold. First, we will evaluate the role
of tobacco smoke and estrogens in determining risk of adenocarcinoma of the
lung among women. Secondly, we will evaluate the role of estrogen receptors and
c-erbB-2 in lung tumors to further understand the pathways through which
estrogen may be acting in the lung. The specific aims are: 1) To conduct a
population-based case-control study of the contribution of tobacco exposure,
estrogen use, and reproductive history in determining risk of adenocarcinoma of
the lung in women. 716 cases will be identified through the Metropolitan
Detroit Cancer Surveillance System of the Karmanos Cancer Institute (a SEER
participant). An equal number of controls will be selected through random digit
dialing. 2) To determine if genotype at the metabolic enzyme loci CYP1A1,
CYP1B1, CYP17, CYP19, GSTM1, GSTP1, COMT, and NQO1 are associated with risk of
adenocarcinoma of the lung in women. These enzymes are active in both the
metabolism of tobacco smoke carcinogens and the synthesis and metabolism of
estrogens. 3) To examine gene-gene and gene-environment interactions, focusing
on tobacco and estrogen effects. 4) To determine estrogen receptor status
(alpha and beta) and c-erbB-2 levels in the lung tumors of women with
adenocarcinoma and evaluate risk associated with tobacco exposure, estrogen
use, reproductive history, and genotype at metabolic enzyme loci by tumor
characteristics.
The proposed study represents a focused approach to defining the contribution
of genes and environments in risk of adenocarcinoma of the lung in women. The
interview component of the study will provide data about individually measured
environmental risk factors. Genotypes have been chosen which impact on
biologically effective dose of tobacco carcinogens and estrogens in the lung.
The study of tumor characteristics will provide insight into mechanism of
action. This large, population-based study should provide clues for important
prevention and therapeutic strategies for lung cancer.
Publications
None