In the US, colorectal cancer is the third most commonly diagnosed cancer in men and women. An increasing
number of studies are suggesting that bacteria play a role in colorectal cancer, including oral bacteria that have
the potential to act as pathobionts. In addition, recent studies have shown that periodontitis is associated with
an elevated risk of colorectal cancer. In a recent Science article, Bullman et al. identified a high relative
abundance of Fusobacterium in many colorectal primary tumors as well as in metastatic tumors, and they also
reported the presence of many other bacteria in colorectal tumors, including bacteria previously associated
with periodontitis (e.g,. Treponema denticola) and colorectal cancer (e.g., Bacteroides fragilis). While
Fusobacterium nucleatum has been studied extensively in relation to colorectal cancer, Porphyromonas
gingivalis, a keystone pathogen for periodontal disease, has been less well-studied, although two studies
suggest it may be associated with colorectal cancer. These studies provide strong rationale to more thoroughly
investigate the role of oral pathobionts in colorectal carcinogenesis. In this R21, in Aim 1 we propose to
evaluate if serum antibodies to 8 periodontal pathobionts are associated with colon cancer risk and will assess
latency up to 25 years in a prospective study of 200 cases and 200 matched controls nested in a cohort with
long follow-up. In Aim 2, we will optimize an existing method for measuring antibodies to periodontal microbiota
in plasma, and then determine the correlation between antibody concentrations in serum and plasma from the
same participants over a 15-year time period. The advantage of using circulating concentration of antibodies
as a measure of exposure to periodontal disease bacteria is that it reflects the extent to which the bacteria
have invaded the host beyond the oral cavity and elicited an immune response. The proposed study will be the
first to examine the association between antibodies to periodontal disease microbiota and colon cancer risk
using prediagnostic blood samples, and by informing on the temporal relationship will provide critical data to
further evaluate the causal role of periodontal microbiota on cancer development in humans.
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