Lung cancer is the leading cause of cancer death in the United States, with African Americans (AAs)
suffering a higher lung cancer incidence than any other ethnic or racial group, for reasons that are poorly
understood. Recent studies have shown that the lungs are inhabited by communities of diverse types of
bacteria and that bacterial infection in the lungs has been associated with lung cancer risk. Recent studies
have also shown that the oral microbiome is the primary source of bacterial microbiota in the lungs and that the
bacterial communities of the lungs overlap those found in the mouth. We found in our pilot study that multiple
bacterial taxa in mouth rinse samples were associated with lung cancer risk. We hypothesize that (1) oral
microbiomes may play a role in the etiology of lung cancer, (2) oral bacteria may interact with cigarette
smoking and chronic lung diseases to influence lung cancer risk, and (3) the oral microbiome of AAs may differ
from that of European Americans (EAs) in ways that could lead to a high incidence of lung cancer in AAs. To
test these hypotheses, we will use already collected data and stored biospecimens from the Southern
Community Cohort Study (SCCS) and Black Women's Health Study (BWHS). Mouth rinse samples were
collected from approximately 39,000 SCCS participants and 28,000 BWHS participants using a similar
collection method. In the proposed study, we will conduct a nested case-control study of lung cancer, with 800
incident cases (600 AAs and 200 EAs) and 1,000 matched controls (600 AAs and 400 EAs), using pre-
diagnostic mouth rinse samples. We will perform whole metagenome shotgun sequencing and use advanced
biostatistics and bioinformatics techniques to investigate oral microbial composition (bacterial species/strains
abundance and diversity) and functional capabilities (bacterial genes/pathways abundance and diversity) for
their associations with lung cancer risk (Aim 1). We will evaluate the possible interaction of oral microbial
communities with other risk factors in relation to lung cancer risk (Aim 2). We will further evaluate whether the
oral microbiome and lung cancer association differs between AAs and EAs and whether African ancestry
modifies the microbiome-lung cancer association (Aim 3). Finally, we will perform in vitro studies to evaluate
potential function of identified bacteria (Aim 4). The proposed study is highly innovative, as there are no
published studies on the association between the oral microbiome and lung cancer risk. The exceptional
resources of the SCCS and BWHS, coupled with state-of-the-art whole metagenome shotgun sequencing and
bioinformatics technologies, provide an unprecedented opportunity to evaluate the role of the oral microbiome
in lung cancer risk. Results from our proposed study will increase understanding of the pathophysiological
effects of microbiomes on the etiology of lung cancer and could provide useful information for preventive
interventions as well as providing new information to ameliorate disparities in lung cancer.
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